Abstract
Recent advances in molecular biology and recombinant DNA (r-DNA) technology have enabled products of animal, plant or microbial origin to be produced in large quantities by culturing bacteria, yeast, plant or mammalian cells. A typical bioprocess will consist of growing cells in a suitable nutrient medium, followed by the recovery and purification of the product: downstream processing. If the desired product is extra-cellular then the first stage in processing will be the removal of large solids and cells by centrifugation or filtration. The broth is then fractionated or extracted into major fractions; this can be done using processes such as chromatography, liquid-liquid extraction or precipitation. The fraction containing the product may then be purified further, often with more specialised chromatographic techniques. However, the majority of products remain intracellular, enclosed in a soluble or insoluble form within the cell. Some of these products are cytoplasmic, others are associated with cell membranes, cell wall components or the periplasm (where present). In this case, the cells must first be harvested to form a concentrated slurry or paste, then disrupted to release their products into solution for subsequent extraction and purification.1. Flow sheets illustrating typical fermentation and downstream processes are shown in Figure 9.1.
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References
Salusbury, T.T. (1989). Disruption. In Harris, E.L.V. and Angal, S. (Eds), Protein Purification Method: A Practical Approach. IRL Press Ltd, Oxford.
Kearns, M.J. (1989). Containment of biological hazards; effect of guidelines on the design of pharmaceutical facilities and process equipment; Pharmaceutical Engineering, 9 (4), 1721.
Bennett, A.M., Benbough, J.E. and Hambleton, P. (1990). Biosafety in downstream processing. In Pyle, D. (Ed) Separations for Biotechnology 2. Elsevier, pp. 592–600.
Dunhill, P. (1982). Biosafety in the large-scale isolation of intracellular microbial enzymes, Chemistry and Industry, 22, 877–879.
Darbyshire, J. (1981). Large scale enzyme extraction and recovery. In Wiseman, A. (Ed), Topics in Enzyme Fermentation Biotechnology, Ellis Horwood, Chichester, Chapter 3, pp. 147–186.
ACGM (1987). Guidelines for the Large Scale Use of Genetically Manipulated Organisms. ACGM/HSE/Note 6.
Leaver, G. and Hambleton, P. (1992). Bioreactor design considerations to minimise or prevent inadvertent release, Pharm. Tech., 4, 18–26.
van Hemert, S.P. and Tiesjema, R.H. (1987). Safety aspects of closed system filtration and ultrafiltration in vaccine production, Swiss Biotech, 5, 13–18.
Krook, G. (1989). Centrifugal separators: technical considerations regarding containment and sterilisation. In Salusbury, T.T. (Ed), Proceedings of the DTI/HSE/SCI Symposium on Large Scale Bioprocessing Safety, 30 November and 1 December, 1988. Warren Spring Laboratory Report Number LR 746 (BT), Stevenage.
Chapman, C. (1989). Client Requirements for Supply of Contained Bioreactors and Associated Equipment. In Proc. Symp. Large Scale Bioprocessing Safety, Ed. T. Salusbury. Warren Spring Laboratory Report LR746 (BT), Stevenage, UK, pp. 58–62.
Matthew Hall (1987). Centrifugal contactors and separators. Matthew Hall Engineering (Southampton) Ltd, PPFB/10/1987. Available from DTI MT Division, Ashdown House, 123 Victoria Street, London.
Alfa Laval (undated) BTUX 510 Contained Separation System for Commercial Biotech Production Reference Number PB 41116E2, 9005, Alfa Laval Separation AB, Tumba, Sweden.
Hemfort, H. and Kohlstette, W. (1984). Centrifugal clarifiers and decanters for biotechnology, Technical Scientific Documentation Number 5, Westfalia Separator AG, Oelde, Germany.
Lawrence, A. and Barry, A. (1982). Potential hazards associated with the large-scale manufacture of bacterial vaccines, Chemistry and Industry, 22, 880–884.
Walker, P.D., Narendranathan, T.J., Brown, D.C., Woolhouse, F. and Vranch, S.P. (1987). Containment of micro-organisms during fermentation and downstream processing. In Verrall, M.S. and Hudson, M.J. (Eds), Separations for Biotechnology. Ellis Horwood: Chichester.
van Hemert, P. (1982). Biosafety aspects of a closed-system Westfalia-type continuous centrifuge, Chemistry and Industry, 22, 889–891.
Hughes, D.E., Wimpenny, J.W.T. and Lloyd, D. (1971). The disintegration of micro-organisms. In Norris, J.R. and Ribbons, D.W. (Eds), Methods in Microbiology, Vol 5B. Academic Press.
Pandolfe, W.D. (1989). The cell disruption homogeniser, In Salusbury, T.T. (Ed), Proceedings of the DTI/HSE/SCI Symposium on Large Scale Bioprocessing Safety, 30 November and 1 December, 1988. Warren Spring Laboratory Report Number LR 746 (BT), Stevenage.
Bennett, A.M. (1991). The integrity testing of the constant systems ultra high pressure cell disrupter. Agenda Item 3.2 Industrial Biosafety Project Meeting Notes November 1991. Warren Spring Laboratory.
Andrews, B.A., Huang, R.B. and Asenjo, J. A. (1990). Differential product release from yeast cells by selective lysis. In Pyle, D. (Ed), Separations For Biotechnology 2. Elsevier.
Harrison, S.T., Dennis, J.S. and Chase, H.A. (1990). The Effect of culture history on the disruption of Alcaligenes eutrophus by high pressure homogenisation. In Pyle, D. (Ed), Separations for Biotechnology 2. Elsevier.
Heppel, L.A. (1967). Selective release of enzymes from bacteria, Science, 156, 1451– 1455.
Asenjo, J.A. (1990). Cell disruption and removal of insolubles. In Pyle, D. (Ed), Separations for Biotechnology 2, Elsevier.
Matthew Hall (1984). Hygienic and aseptic pumps for the biotechnology industry. Matthew Hall Engineering (Southampton) Ltd, PPFB/4/1984. Available from DTI MT Division, Ashdown House, 123 Victoria Street, London.
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Deans, J.S., Stewart, I.W. (1994). Containment in downstream processing. In: Hambleton, P., Melling, J., Salusbury, T.T. (eds) Biosafety in Industrial Biotechnology. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-1352-6_9
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DOI: https://doi.org/10.1007/978-94-011-1352-6_9
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