Process-scale chromatography

The cleaning of process-scale chromatography systems used in the purification of biopharmaceuticals can also present challenges. Although such systems are disassembled periodically, this is not routinely undertaken after each production run. CIP protocols must thus be applied periodically to such systems. The level and frequency of CIP undertaken will depend largely on the level and type of contaminants present in the product-stream applied. Columns used during the earlier stages of purification may require more frequent attention than systems used as a final clean-up step of a nearly pure protein product. While each column is flushed with bulfer after each production run, a full-scale CIP procedure may be required only after every 3-10 column runs. Most of the contaminants present in such columns are acquired from these previous production runs. 

In the late 1990s he was involved in the installation and commissioning of process scale HPLC at Zeneca Pharmaceuticals. During 18 years with CRB, ICI, Zeneca and Avecia he was instrumental in establishing the technique of preparative HPLC within the company and served 11 years as the secretary of the company s Process Scale Chromatography Group. 

Immobilized metal affinity chromatography has been shown to be effective for isolating proteins from crude mixtures, as well as for selective separations of closely related proteins [2]. With respect to separation efficiency, IMAC compares well with biospecific affinity chromatography and the immobilized metalion complexes are much more robust than antibodies or enzymes. These factors make IMAC particularly well suited for scale-up to process scale chromatography. The main scale-up points to be aware of are the degree to which the column is metal saturated, the chelating agent content of the sample, and the potential of leached metal (or its interactions) within the product eluate. 

Liquid-liquid extraction also can be an attractive alternative to separation methods, other than distillation, e.g., as an alternative to crystallization from solution to remove dissolved salts from a crude organic feed, since extraction of the salt content into water ehminates the need to filter solids from the mother liquor, often a difficult or ejq)ensive operation. Extraction also may compete with process-scale chromatography, an example being the recovery of hydroxytyrosol (3,4-dihydrojq -phenylethanol), an antioxidant food additive, from olive-processing wastewaters [Guzman et al., U.S. Patent 6,849,770 (2005)]. 

Another stimulating factor was the breakthrough in the development in process-scale chromatography around this time. During 1993 the first scaled-down versions of SMB units had been presented for use in pharmaceutical product recovery, focusing on enantiomer separation. This triggered discussion on how to develop generic approaches for quick method development and implementation, and led to the... 

G. Jagschies, Process-Scale Chromatography, in Ullmann s Encydopedia of Industrial Chemistry, Vol. B, VCH, Weinheim, 1988. 

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