ses of 'older' fermentation processes split approximately 1:1 between fermentation costs and isolation/purification costs (Reisman, 1993). However, the change in the last 10 years to use recombinant organisms to produce exotic compounds at extremely low titres has meant that the fermentation/ isolation-purification split may be 1:8 or 1:10. This means that the fermentation may only be 10% of the costs, while the recovery accounts for 90%. In this case the correct choice of the recovery-purification procedure can be crucial to the success of a process and early evaluation of alternative techniques may be very important.

Stowell and Bateson (1984) identified a number of factors contributing to these costs:

1. Yield losses, even if only modest, are certain to occur at each stage of the recovery process.

2. High energy and maintenance costs associated with running filtration and centrifugation equipment.

3. High costs of solvents and other raw materials used in recovery and refining of products.

Atkinson and Mavituna (1991) reported losses of 8% for citric acid and 4% for penicillin G in the recovery and purification stages before conversion to the potassium salt in production processes. They also stressed the importance of trying to reduce the number of downstream stages as much as possible to reduce capital and operating costs.

It is thought that depreciation, return on capital and maintenance can account for over 80% of the overall cost for a large-scale rotary filtration or centrifugation plant (Atkinson and Mavituna, 1983). However, it is considered that removing cells by filtration is less energy consuming than by centrifuging. If filter aids are to be used, in the most economical way, this will still add £9 tonne"1 for a product at a 10% concentration in the broth.

One of the main factors affecting centrifuge economics is the size of the particle to be separated (Asenjo, 1990). Filtration costs are less dependent on particle size. At a particle size greater than 1 to 2 pm, centrifugation is more economical. Below this size ultrafiltration becomes more economical.

Taksen (1986) has given a case study for a moderate value product (£1.50 to 3.00 per kg) requiring the processing of 200,000 dm3 of broth per day by rotary vacuum filtration or centrifugation. Capital investment for the rotary filter would be £500,000 with an operating cost of 1.15 p per dm3 of broth. A three-stage centrifuge would cost £667,000 and broth could be processed at 0.62p per dm3. Because rotary filters were already available, it was decided that the new capital investment could not be justified, although the broth would cost more to process. In another case study on ultrafiltration vs. evaporation to pre-concentrate a moderately high-molecular-weight product, the cost of water removal by membrane techniques was estimated to be 40% lower than by evaporation.

Maiorella et al. (1984) have compared extraction processes in 11 alternative ethanol fermentation processes. Selective ethanol removal by flash distillation was thought to be the most economic technique.

When a product may be made by a microbial process or obtained from an alternative source there are cost limits on product recovery to be considered. Atkinson and Mavituna (1991) estimated:

1. A limit of about £40 tonne"1 for ethanol selling at £220 tonne"1 produced at 7% w/v in broth from a local source of carbohydrate.

2. A limit of about £100 tonne"1 for SCP selling at £300 tonne"1 produced from a petroleum-based substrate to give a 3% w /v yield.

3. A limit of about £300 tonne"1 for organic acids or glycol selling at £700 tonne"1, produced at 10% concentration in a carbohydrate medium.

When high-value end-products have been produced it has been acceptable to use relatively large weights of filter aid to achieve initial clarification to remove small amounts of solids. The solvents used in subsequent extraction have then been recovered in a high energy-consuming distillation plant (Atkinson and Sainter, 1982). In this case, the manufacturer has only to make his product as economically as those of other fermentation companies.

Before certain products may be marketed the extraction/purification procedure will have to be validated (approved) by the FDA (U.S.A.) or similar regulatory bodies. Any changes in extraction procedures will have to be checked for revalidation, which will incur further costs (Reisman, 1993). Therefore, if validation is to become an issue in processing it may be worthwhile having alternative procedures validated at an early stage in development.

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