This is taken from a teaching exercise published in BINARY.

While batch culture has cell concentration, medium concentration, pH, products, viscosity, and other properties changing, continuous cultivation achieves steady state or shows small excursions from it. Relating cause and effect during experimentation is far easier for continuous fermentation. This great advantage for research is not a convincing argument for commercial processing where there must be cost advantages for continuous culture to be selected over batch.

The BASIC program, GOALS.BAS, uses medium composition, costs of ingredients, operating costs, and purification costs to plot families of curves to show the effects of vessel size on batch fermentation costs and of dilution rate or titer on costs of continuous fermentation. Some assumptions greatly oversimplify the cost analysis. When the composition of the medium is the
same for batch and continuous operation, this cost cancels out. However, it may require a great deal of research on continuous cultivation to reach high titers of product. Operating costs are a different matter because better productivity for continuous fermentation results in savings; more product per day with the same cost for operating the vessel is highly advantageous.
A product such as penicillin that is extracted from the broth with an immiscible solvent is extracted back into water at a concentration to match subsequent purification steps. This means that it matters little in terms of purification whether the fermentation is batch or continuous. If the solvent to broth ratio is fixed, the solvent cost is also unaffected by continuous operation.

Some graphs drawn by the computer program are shown as Figures 1 through 4. It is surprising how small is the cost advantage of continuous operation as dilution rate increases. Also unanticipated is the small effect of titer after the region of low titers is passed. This is explained by the purification cost dominating so much that fermentation cost becomes a minor factor.
Figure 1.  Effect of vessel size on batch cost

Figure 2.

Figure 3. Effect of dilution rate and comparison with batch cost.

Figure 4. Effect of titer (product concentration) at a fixed dilution rate.

Higher titer usually means higher purity at each step throughout the process. This should translate into better step yields and perhaps development of a better purification scheme. The computer program increases the recovery yields as titer improves.

The program seems to have little interactivity, but in fact, there is potential to perform many "what if" experiments on the composition of the medium and the assumptions for operating and purification costs. The educational benefits are the insights from interpretting the graphs and criticizing the cost assumptions. For example, the operating costs are mere guesses, and the dependencies on vessel size are debatable. The points of special interest are:

   1.While there is a significant cost benefit in switching from batch to continuous operation (if
     titer does not suffer), there is very little cost improvement as the dilution rate gets higher and
     higher.
   2.Higher titer is better, but again returns diminish past a certain titer.
   3.Size of the bioreactor matters greatly but not after large sizes are reached.

In other words, the most cost effective reseach should aim for a good titer at a reasonable dilution rate in a large vessel. Then the focus should shift to a less expensive medium or more cost effective recovery of the product.