Scale cell culture, biologies

The 1980 s and the early 1990 s have seen the blossoming development of the biotechnology field. Three-phase fluidized bed bioreactors have become an essential element in the commercialization of processes to yield products and treat wastewater via biological mechanisms. Fluidized bed bioreactors have been applied in the areas of wastewater treatment, discussed previously, fermentation, and cell culture. The large scale application of three-phase fluidized bed or slurry bubble column fermen-tors are represented by ethanol production in a 10,000 liter fermentor (Samejima et al., 1984), penicillin production in a 200 liter fermentor (Endo et al., 1986), and the production of monoclonal antibodies in a 1,000 liter slurry bubble column bioreactor (Birch et al., 1985). Fan (1989) provides a complete review of biological applications of three-phase fluidized beds up to 1989. Part II of this chapter covers the recent developments in three-phase fluidized bed bioreactor technology. 

The most widespread biological application of three-phase fluidization at a commercial scale is in wastewater treatment. Several large scale applications exist for fermentation processes, as well, and, recently, applications in cell culture have been developed. Each of these areas have particular features that make three-phase fluidization particularly well-suited for them Wastewater Treatment. As can be seen in Tables 14a to 14d, numerous examples of the application of three-phase fluidization to waste-water treatment exist. Laboratory studies in the 1970 s were followed by large scale commercial units in the early 1980 s, with aerobic applications preceding anaerobic systems (Heijnen et al., 1989). The technique is well accepted as a viable tool for wastewater treatment for municipal sewage, food process waste streams, and other industrial effluents. Though pure cultures known to degrade a particular waste component are occasionally used (Sreekrishnan et al., 1991 Austermann-Haun et al., 1994 Lazarova et al., 1994), most applications use a mixed culture enriched from a similar waste stream or treatment facility or no inoculation at all (Sanz and Fdez-Polanco, 1990). 

Comprehensive descriptions of the basic unit operations commonly used in the production of biotechnology products are available in the literature (14). This section focuses on the typical unit operations currently used for production of biological molecules in cell culture and the technologies used for the purification of pharmaceutical proteins. For each of these operations, laboratory and pilot scale experiments provide the basis for scale-up, particularly to define the expected range of process operating parameters. 

S. N., Insect cell culture for industrial production of recombinant proteins, Appl. Microbiol. Biotechnol. 62, 1-20, 2003 Kallos, M.S., Sen, A., and Behie, L.A., Large-scale expansion of mammalian neural stem cells a review, Med. Biol. Eng. Comput. 41, 271-282, 2003 Schiff, L.J., Review production, characterization, and testing of banked mammalian cell substrates used to produce biological products in vitro, Cell Dev. Biol. Animal 41, 65-70, 2005 Evan, M.S., Sandusky, C.B., and Barnard, N.D., Serum-free hybridoma culture ethical, scientific, and safety considerations, Trends Biotechnol. 24, 105-108, 2006. 

Vorlop J Lehmann J (1989) Oxygen transfer and carrier mixing in large-scale membrane stirrer cell culture reactors. In Spier RE, Griffiths JB, Stephenne J Crooy PJ (eds) Advances in Animal Cell Biology and Technology for Bioprocesses, pp. 366-369. Butterworth, London. 

Quality assurance by means of strict quality control of all aspects of a cell culture process has always been of prime importance, given the sensitivity of cells to sub-optimal medium and environmental factors and the ease with which cells can become contaminated with viruses and other microorganisms. The potential for biological changes in scale-up of cell culture processes demands even greater standardization and testing of the system. 

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