Expense, manufacturing-operating scale

These scale-up issues present some of the more difficult challenges in crystallization processes, as they do for other engineering operations. In most cases, the products obtained may be handled but with increased capital and operating expense for the cumbersome downstream operations. These costs may exceed those of the other steps in a manufacturing operation. In extreme cases, the products may be unsuitable for commercial use because of the poor physical properties discussed above. 

True models involve building all significant process features to scale. Thus the model is an exact replica of the prototype, that is, of the commercial plant. We build true models in some safety investigations to determine definitely the cause of a specific, safety event. Automobile manufacturers use true models when gathering crash data about the vehicles they plan to market. For complex processes, a complete model is actually a full-scale prototype, that is, a true model [7]. While true models may provide highly accurate information, they are capital intensive, expensive to operate, and require extended time periods to build. 

Reactions that are simple in a laboratory can be too expensive to operate on a manufacturing plant scale. When expense and profitability are of no concern, anything that can be done in a laboratory can be done in a plant. When constraints of a practical process are overpowering, a project may have to be abandoned. If a process can be implemented in a manufacturing plant, the manufacturing plant will usually prepare products superior to those made in a laboratory. Without the engineer s skill and knowledge most new processes would never function properly or become profitable. 

An alternative source of the ethyl component was ethyl bromide, a less expensive material. It was at this point that GM called upon DuPont to take over process development. DuPont was the largest U.S. chemical company at the time. It had extensive experience in the scale-up of complex chemical operations, including explosives and high-pressure synthesis. The manufacturing process was undertaken by DuPont s premier department, the Organic Chemical section. GM contracted with DuPont to build a 1,300 pound per day plant. The first commercial quantities of TEL were sold in Februai-y 1923 in the form of ethyl premium gasoline. 

Variable costs become relatively more important, constituting an increasingly large proportion of the total costs, as the scale of operation increases and especially as the manufacturing process is simplified, thereby decreasing the requirement for expensive... 

Many factors act together to determine the optimum scale of a process. These include the demand for the product, competitors share of the market, any technical limitations on the size of operation and also economies of scale effects. There is an approximate logarithmic relationship between the unit production costs for a product and the volume of production, whereby considerable economies of scale can be achieved. If the costs of a process of one size (C ) is known then the costs of larger or smaller factories (C ) can be approximately obtained from the relationship C = Cx (or n° ), where n is the scale-up ratio, i.e. n=l for a plant that is twice as big. Alternatively, a graph of log capital costs vs. log of plant capacity gives a straight line with a slope equal to the scale-up factor (n). The power term varies from case to case, but is invariably less than one. This scale effect is one reason why unit production costs are inversely proportional to the scale of manufacture. For example, most amino acids are expensive and can only be used in... 

Pilot plant experimentation is expensive and can be time consuming, delaying the introduction of the product in the marketplace. There have been trends and reports of recent successes whereby extensive pilot plant research has been bypassed. One such study involved the manufacture of bisphenol A in which laboratory work bypassed the pilot plant stage and a full-scale production unit was designed and operated successfully. This is not recommended, but using some laboratory research and simulation, may make it possible to reduce or eliminate expensive pilot plant work. However, confidence must be developed in using simulation to replace pilot plant work and this is obtained only through experience. 

Equipment for preparative HPLC is relatively expensive. To maximize its utility, it should be specified with autoinjection to run unattended and collect previously identified peaks. A 30-min cycle is typical so that overnight operation can process over 30 portions of feed solution. This appears to be the best option for maximizing output with bench-scale apparatus. There is also the advantage that the separation can be fine-tuned during the course of the operation. A number of manufacturers supply equipment based on columns of 15— 50 mm diameter packed with stationary phases of 5-15 pm. Retention times in reverse phase HPLC can be influenced by temperature. It is recommended that a column used for repetitive injection be housed in an oven set at a temperature slightly higher than ambient, e.g., 30°C. 

The ultimate desire is to operate the pilot plant with the assurance that all the risks, both technical and economic, in the full-scale commercial plant have been minimized or, preferably, eliminated. The pilot plant must be capable of operating over relatively long periods under conditions that are not changed frequently, to obtain a fair approximation of labor costs and manufacturing expenses. In a pilot plant the pieces of equipment are selected specifically for the work to be performed. It should not be dismantled until such times as the full-scale commercial plant is in successful operation, because it is the place where quality and manufacturing improvements are worked out. 

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