The cost of the various components of a production medium can have a profound effect on the overall cost of a fermentation process, since these account for 38 to 73% of the total production cost (Table 12.1). The organic-carbon source in microbial processes is usually the most expensive component contributing to the cost of the process. Ratledge (1977) has made a detailed analysis of annual price and availability of major carbon substrates. The price of a natural material may fluctuate due to other competing demands and the annual variation in the quantity harvested. Big capital investment may be tied up in natural materials if they are seasonal and require storage. Hastings and Jackson (1965) stated that up to 23 x 106 dm3 of molasses may have to be stored for an industrial alcohol-production process. A particular material may be selected because it is cheap locally, rather than the best substrate (Calam 1967).
In a cost study analysis for tissue plasminogen activator by a mammalian-cell process, fermentation materials accounted for 75% of the total raw materials cost (Datar et al., 1993). Of this cost, calf serum was estimated to contribute 73% or 55% of the total cost. However, it has been possible to develop a serum-free medium for economic production of antibodies from hybridoma cells (Maiorella, 1992).
In the search for suitable nutrient components for media, six criteria were considered in Chapter 4 which ought to be satisfied whenever possible. Ratledge (1977) has stressed the need to note the amount of carbon in a carbon substrate when costing. Higher yields might be achieved by changing from a carbohydrate to an alternative carbon source, but increased aeration and/or agitation rates may be necessary with the change in substrate. The cost of this extra provision must therefore be less than the savings from the change of substrate if the process is to be feasible. When cheapness is added as a further restraint the number of potential major nutrients which could be used on an industrial scale is limited. Carbohydrates from beet, sugar cane or grain are the major carbon and energy sources in most media and comply with the requirements of economy and those stated in Chapter 4. In 1993, sugar and starch based fermentation substrates were available within the EEC for approximately £200 tonne"1. However, these are commodities whose cost fluctuates according to supply and demand. It is therefore worthwhile to develop a series of cost optimized media formulations so that the most cost effective growth medium can always be used when necessary (Winkler, 1991).
During the 1970s there was considerable interest in using petrochemicals as substrates for SCP production as protein animal feed by a number of major chemical and petroleum companies (Sharp, 1989). A number of processes were developed using methane or methanol as the main carbon substrate. None are now being operated. Major factors which contributed to making these processes uncompetitive included the increased cost of the substrate (see Chapter 4) and the availability of cheaper alternative animal feeds.
A variety of waste materials would seem to be potential cheap carbon sources. Unfortunately, it has been shown that their use is very restricted because they cannot compete economically with conventional substrates. This may be due to a number of possible reasons including variability of the material, impurities which make downstream processing more difficult, high water content making transport costly, geographical location, quantities produced and limited seasonal availability. The economics of biomass production from whey have been reviewed by Meyrath and Bayer (1979). The possible use of waste substrates may depend on the cost of alternative methods of disposal or on the availability of government grants to diminish pollution (Perlman, 1970).
Mineral components normally constitute a smaller part of the cost of media, e.g. they account for 4 to 14% of the manufacturing cost of single-cell protein (Cooney and Makiguchi, 1977). Although feed grades of phosphates are more expensive than fertilizer grades, they do not contain impurities such as iron, arsenic and fluoride. This is an important consideration in the production of foods and drugs (Litchfield, 1977). The hydroxides and sulphates of potassium, magnesium, manganese, zinc and iron are preferred to the chlorides to minimize corrosion of stainless steel. The source of basic materials can cause considerable variation in product yield. Corbett (1980) compared six samples of calcium carbonate, and found that five of them reduced the titre of penicillin G in a production medium.
Problems concerned with the storage, handling and mixing of media should not be neglected. Powders must be kept in dry conditions because of the possibility of substances becoming rock-like or glutinous. Some bulk liquids with a high solids content need to be kept warm to prevent them solidifying, e.g. glucose and corn-steep liquor. If storage temperatures are too high there could be degradation. It is also vital for workers to follow instructions for media preparation very carefully to prevent 'lumpy' media, etc. (Corbett, 1980).
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