Plant costs process chromatographs

The components of a commercial process employing chromatographic separation are represented on the flowsketch of Figure 15.28. The process is intermittent with very short cycles. The cost breakdown of a plant for the separation of a- and j8-pinenes is given in Table 15.7, which is based on pilot plant work in a 4 in. dia column. That company is no longer in that business thus the test... 

Chromatographic separations with product purities exceeding 99% and high separation costs require precise prediction of the optimal process design. This demands carefully validated models, especially in the separation sections of the SMB plant. Consequently, methods are needed to increase the number of measured data points. 

Multipurpose flexibility is another major requirement for process engineering given the high costs associated with process equipment and modern plants. Nowadays, plants are not built just for one single product they have to cope rather with a certain variety of products. Some of the major multipurpose considerations are straightforward, for example the use of chromatographic resins that are chemically and physically robust and easy to clean. There are other issues that are less obvious and have to be considered early in the research activities, like the use of full traceable cell lines and the use of endotoxin-free components supplied with certificates of analysis (Aldington and Bonnerjea, 2007). 

Because of the uncertainty of sample delivery times, rapid/fast IPC chromatographic methods are needed to maintain an efficient analytical laboratory and plant operation.Since many samples can be generated during the process development, IPC methods should be developed and optimized for the shortest analysis time possible. The need for a fast IPC method was demonstrated by Wu et al. who redeveloped an in-process method to shorten the run time for a reaction conversion HPLC analysis from 30 to 10 min using a monolithic HPLC column.The newly developed method could also be used to determine mother liquor concentrations and perform impurity profiles for the crude product. This optimized method reduced the process cycle time for lab instrumentation. The dual purpose for an IPC method (i.e., COR, impurity profiling, and/or concentration analysis) is another opportunity to improve the process and lab efficiency. Another example of a dual-purpose method use was demonstrated by Nageswara Rao et al. who developed a 15-min RP-HPLC method that could determine the COR and impurity profile (isolated product) for two different processes for production of 4-methoxyphenyl acetic acid." The dual-purpose method is a common theme for in-process analyses. It is also important to remember that a reduction in the analysis time and overall manufacturing time can reduce the cost of the API. 

In consideration of the above it is therefore essential to ecamine, as widely as possible within the time available, all of the alternatives which are available to the chromatographer, in order to develop the required safe, reliable and cost-effective process. Throughput must be maximised in order to minimise the use of often flammable, toxic and costly solvents and to minimise expenditure on plant, equipment, labour and operating costs. 

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