A methodology for the comparative evaluation of alternative bioseparation technologies

Abstract

Advances in upstream technologies and growing commercial demand have led to cell culture processes of ever larger volumes and expressing at higher product titers. This has increased the burden on downstream processing. Concerns regarding the capacity limitations of packed-bed chromatography have led process engineers to begin investigating new bioseparation techniques that may be considered as "alternatives" to chromatography, and which could potentially offer higher processing capacities but at a lower cost. With the wide range of alternatives, which are currently available, each with their own strengths and inherent limitations, coupled with the time pressures associated with process development, the challenge for process engineers is to determine which technologies are most worth investigating. This article presents a methodology based on a multiattribute decision making (MADM) analysis approach, utilizing both quantitative and qualitative data, which can be used to determine the "industrial attractiveness" of bioseparation technologies, accounting for trade-offs between their strengths and weaknesses. By including packed-bed chromatography in the analysis as a reference point, it was possible to determine the alternatives, which show the most promise for use in large-scale manufacturing processes. The results of this analysis show that although the majority of alternative techniques offer certain advantages over conventional packed-bed chromatography, their attractiveness overall means that currently none of these technologies may be considered as viable alternatives to chromatography. The methodology introduced in this study may be used to gain significant quantitative insight as to the key areas in which improvements are required for each technique, and thus may be used as a tool to aid in further technological development.