High performance liquid chromatography process scale

K. Jones, Process scale high-performance liquid chromatography. Part I An optimisation procedure to maximise column efficiency, Chromatographia, 25 (1988), 437-442. 

Many different products are now purified by chromatographic processes, from the laboratory scale (a few grams) up to the industrial pharmaceutical scale (a few tons per year) or even up to the petrochemical scale (100,000 tons per year). Among the possible technologies, the elution high-performance liquid chromatography (HPLC) technology (sometimes with recycle) has taken a very important part of the small-scale (10 tons per year) market... 

There are few processes that can be predictably scaled up from laboratory to production scale without difficulties. Preparative high-performance liquid chromatography (HPLC), for example, is not a linear scale-up it is expensive and uses large volumes of solvents. The product can become hydrolyzed by or react with the column, which can induce chemi-cal/steric/chiral conformation changes and often requires significant prepurification with further risk of degradation. 

The technology of high performance liquid chromatography has been successfully extended from the analytical scale to the process scale. The ability to control the various operation parameters to scale up directly from the laboratory to the pilot plant and beyond to the production environment has been developed. This technology can be combined with other separations technologies, such as membrane separations, to provide particle-free solvents, ultrapure products, and concentrated product streams. This will give the opportunity to deal with future separations problems of the chemical process industry. 

Packed bed, process scale high performance liquid chromatography (HPLC) equipment was first introduced by Millipore and Elf Aquitaine in 1982 [105] Since then, several companies, listed in Table 20, have entered the large scale HPLC market. The systems use packed beds at moderate pressures (30-140 bar). While there are substantial time-savings in using these systems compared to other purification techniques, the short life of the packing material and its high cost continue to restrict this technique to applications that warrant the 100/kg separation cost. 

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