Abstract

The large scale purification of proteins and other bioproducts is the final production step, prior to product packaging, in the manufacture of therapeutic proteins, specialty enzymes, diagnostic products, and value added products from agriculture. These separation steps purify biological molecules or compounds obtained from biological sources, and hence, are referred to as bioseparations. The essence of large scale bioseparations is both art and science. Bioseparations often evolve from laboratory-scale techniques. These are adapted and scaled up to satisfy the need for larger amounts of extremely pure, test quantities of the product for analysis, characterization, testing of efficiency, clinical or field trials, and finally, full-scale commercialization. The uncompromising standards for product quality, driven by commercial competition, end-use applications, and regulatory oversight, provide many challenges to the scale-up of protein purification. The rigorous quality control of manufacturing practices embodied in current good manufacturing practices, and the complexity and lability of the macromolecules being processed provide other practical issues which must be addressed.

This article gives an overview of manufacturing approaches for selected bioproducts by the new biotechnology and how these approaches impact their recovery and purification using various bioseparation techniques. The basic theory of the most prevalent bioseparations method, chromatography, is described. Since the literature has presented the theory principally for analytical systems, application which are useful in scaling up process chromatographic separations are reviewed here. Also the reader is provided with practical tools that can be used to initiate the scale-up of liquid chromatography starting from a minimum amount of laboratory data. The use and mechanisms of action of selected bioproducts are summarized to illustrate how recombinant biotechnology provides unique tools and facilitates new products which could not be obtained by other means.