Process chromatography : Five decades of innovation

Abstract

This article explores the development of process chromatography. Process chromatography was first applied to the removal of low molecular weight solutes from whey by gel filtration about 50 years ago. An analytical method using size exclusion chromatography was scaled up for insulin production in the 1970s, when ion exchange became a viable technology for the same application. Ion exchange was adopted as the industry workhorse as robust resins became available and formed the backbone of chromatographic processing of blood plasma fractionation in alternatives to and extensions of ethanol precipitation. Cost restrictions kept affinity chromatography in the laboratory until the production of MAbs made efficient immunoaffinity indispensable in high purity coagulation factor production in the 1980s. Since then, spurred on by the advent of biotechnology, an extensive toolbox of chromatographic methods has been developed, and a process chromatographic capture-purify-polish regime is ubiquitous. Affinity capture of antibodies on Protein A adsorbents is used throughout the industry with widespread discussion of affinity versus ion exchange. The emerging debate pitches chromatography against membrane separations. Column technology has advanced, but not to the plug-and-play status of membrane technologies. Axial flow systems still dominate, but advances in engineering may make radial flow accessible and technologies such as expanded beds more attractive. Process chromatography stands at the threshold of industrialization.