Bioreactors large scale

The introduction of the koji process to the West is chiefly due to the work of Takamine, which started in 1891 in the USA using wheat bran to make the preparation named Taka-Koji. Takamine introduced the technique of acclimatizing the mold to various antiseptics in order to minimize growth of contaminants during the process. The process was carried out on an industrial scale in rotating drum bioreactors. Large scale trials of the use of Taka-Koji instead of malt in distilleries were carried out in the plant of Hiram Walker Sons in Ontario Canada in 1913. This was marketed as a digestive aid imder the name of Takadiastase [8]. 

For large-scale bioreactors (21), especially those of the air lift type (22), the gas phase is best considered as being in plug dow, so that a log mean value of driving force is obtained ... 

Alternatively, some subunit viral vaccines can be generated by rDNA techniques and expressed in a continuous ceU line or insect ceUs. Recent advances in bioreactor design and operation have improved the successful production of IPV in large-scale bioreactors. However, roUer bottles or flasks are stiU used for most current vaccine production. Development of insect ceU culture will allow for very large-scale Hquid suspension culture (143). Several vaccine candidates such as gpl60 for HIV and gD protein for herpes have been demonstrated in the insect ceU culture system. However, no vaccine has been approved for human use. 

True. Pressure-cycle bioreactors have controllable and predictable flow patterns, which makes scale-up more predictable. Factors such as OTR and heat transfer are easier to arrange at large scales. 

The growth of cells on a large scale is called industrial fermentation. Industrial fermentation is normally performed in a bioreactor, which controls aeration, pH and temperature. Microorganisms utilise an organic source and produce primary metabolites such as ethanol,... 

A bioreactor is a vessel in which an organism is cultivated and grown in a controlled manner to form the by-product. In some cases specialised organisms are cultivated to produce very specific products such as antibiotics. The laboratory scale of a bioreactor is in the range 2-100 litres, but in commercial processes or in large-scale operation this may be up to 100 m3.4,5 Initially the term fermenter was used to describe these vessels, but in strict teims fermentation is an anaerobic process whereas the major proportion of fermenter uses aerobic conditions. The term bioreactor has been introduced to describe fermentation vessels for growing the microorganisms under aerobic or anaerobic conditions. 

The calculation of heat transfer film coefficients in an air-lift bioreactor is more complex, as small reactors may operate under laminar flow conditions whereas large-scale vessels operate under turbulent flow conditions. It has been found that under laminar flow conditions, the fermentation broths show non-Newtonian behaviour, so the heat transfer coefficient can be evaluated with a modified form of the equation known as the Graetz-Leveque equation 9... 

Factoring for scale-up, we make some assumptions and may use a few known correlations to progress our calculations. Let us say PaV=D-3, HID = 1 and D/Dt = 3. Also, use constant power per unit volume for the small- and large-scale bioreactor. 

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. 

In this review, we focus on the use of plant tissue culture to produce foreign proteins that have direct commercial or medical applications. The development of large-scale plant tissue culture systems for the production of biopharmaceutical proteins requires efficient, high-level expression of stable, biologically active products. To minimize the cost of protein recovery and purification, it is preferable that the expression system releases the product in a form that can be harvested from the culture medium. In addition, the relevant bioprocessing issues associated with bioreactor culture of plant cells and tissues must be addressed. 

Mammalian cell suspension cultures are the preferred choice for large-scale recombinant protein production in stirred-tank bioreactors. The most widely used systems are Chinese hamster ovary (CHO) cells and the murine myeloma fines NSO and SP2/0. In half of the biological license approvals from 1996-2000, CHO cells were used for the production of monoclonal antibodies and other recombinant glycosylated proteins, including tPA (tissue plasminogen activator) and an IgGl fusion with the tumor necrosis factor (TNF) receptor, the latter marketed as Enbrel [7]. 

Yabannavar et al. [81] used Eqs. (19) and (20) for scale-up purposes. Based on successful operation conditions determined for an existing 12-L bioreactor, they calculated the spin-filter dimensions and operation conditions for an existing 175-L bioreactor. Experiments with the spin-filter designed for the large-scale bioreactor resulted in an absence of filter clogging with cell retention efficiency similar to the 12-L bioreactor. This was considered as an evidence that the suggested scale-up strategy is adequate. 

It has been reported that insect cells have a strong internal buffering capacity [85] however, there are indications that medium pH must be optimised for growth and production phases and should be kept under tight control in bioreactors, especially in high-density large scale cultivations [56]. 

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