Production-scale mammalian cell culture

The combination of three-phase fluidization and cell culture may represent an ideal union of new technology and immediate application because the high-value products of mammalian cell culture require relatively small production scales (on the order of 100 liters rather than 100,000 liters), it is possible to investigate the usefulness of three-phase fluidization in what would otherwise be considered a pilot scale set up without having to build an expensive, large scale unit. 

Mammalian cells are commonly employed for the production of therapeutic and diagnostic proteins, since they are able to correctly synthetize the large and complex structures that the human body requires as medicine [1]. Nowadays, they are employed for the large-scale production of recombinant therapeutic proteins, monoclonal antibodies (MAbs) and viruses used in the preparation of vaccines (e.g. against rabies, hepathytis B, polio, etc) [2]. An overview of some licensed/approved products derived from mammalian cell culture is given in Table 1. 

Transgenic plant systems have the potential to produce recombinant proteins on a commodity scale (Kusnadi et al., 1997) due to the low cost of growing plants and because scale-up of production simply requires sewing seeds over a greater field area. As such they offer almost unlimited scalability (Giddings, 2001). It is estimated by Kusnadi et al. (1997) that transgenic plants can produce pharmaceutical proteins at between 10 and 50-fold lower cost than microbial fermentation systems, and 1,000 times lower than mammalian cell culture systems (Hood et al., 2002). 

Petricciani, J.C. (1985). Regulatory considerations for products derived from the new biotechnology. In Large-scale Mammalian Cell Culture. J.Feder and W.R.Tolbert, eds. (New York Academic Press), pp. 79 86. 

J. Tree, C. Riehardson, A. Fooks, J. Clegg, D. Looby, 2001. Comparison of large-scale mammalian cell culture systems with egg culture for the production of influenza virus A vaccine strains. Vaccine 19, 3444-3450. 

Garnick R L (1998). Raw materials as a source of contamination in large-scale cell culture. In F Brown, E Griffiths, F Horaud, J C Petricciani (eds.), Safety of Biological Products Prepared from Mammalian Cell Culture, Vol. 93, Dev. Biol. Stand. Karger, Basel Switzerland, pp. 21-29. 

Whitford (48) provides mnch more information that is of interest to chemical engineers involved in the design and operation of fed batch processes for culture of animal cells. Shukla and Thommes (49) discnssed additional aspects of fed batch culture of mammalian cells for large scale production of monoclonal antibodies and related proteins. Further information concerning the use of bioreactors for culture of mammalian cells is contained in the article Mammalian Cell Bioreactors by Zhou and co-workers in the Encyclopedia of Industrial Biotechnology (50). 

Dors, M., Simutis, R., Ltibbert, A. (1995) Hybrid process modeling for advanced process state estimation, prediction and control exemplified at a production scale mammalian cell culture. In Recent Advances in Biosensors, Bioprocess Monitoring, and Bioprocess Control, K.R. Rogers, A. Mulchandani, W. Zhou, Eds., ACS Symposium Series, American Chemical Society, Washington, D.C. (this vol.)... 

Hybrid Process Modeling for Advanced Process State Estimation, Prediction, and Control Exemplified in a Production-Scale Mammalian Cell Culture... 

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