Facing the Challenges in Bio-Pharmaceutical Production: Developments in Ion Exchange Media to Bring Down Cost of Goods

As the bio-pharmaceutical industry matures, terms like ‘cost of goods’ are becoming more and more important. Up to now, strain optimisation for high productivity and upstream purification were the bottleneck for most bio-processes. However, with the progress made in recent years, titers in fermentation processes have increased significantly. Obviously, this increased volumetric productivity will help reducing the cost of goods, but it also has an impact on the downstream processing. Therefore, improved downstream processing media are required to process the increased product load in the same timeframe. Recently, new materials, based on fully synthetic polymer based matrices became available and show important advantages over traditional polysaccharide-derived media. In the following article the focus is on ion exchange chromatography (IEX) as an important step in the biopharmaceutical process.

BASICS OF ION EXCHANGE CHROMATOGRAPHY
IEX has been used for many years for analysis and purification of bio-molecules [1]. Its simple concept of charge induced reversible binding has several important advantages, two of which are: binding is fast and media
show a high capacity. Also, compared with other chromatographic methods, such as hydrophobic interaction chromatography (HIC) or mixed mode resins, method development is straightforward. The binding/elution
behaviour can be described by a simple ‘on/off’ mechanism. The molecules will bind to the chromatographic support at low ionic strength at a pH below (for cation exchange) or above (for anion exchange) its isoelectric point. Release will take place at increased ionic strength or by pH shift. In both cases, there is a distinct and narrow zone of pH/salt concentration, which determines whether there is binding or not. This also means that isocratic elution is not possible with IEX. Simple salt (step) gradients are most commonly used for elution. Stationary phases are generally resistant to a wide range of pH. All these characteristics make the technique ideal for the two main process steps of capture and (intermediate) purification. In addition final polishing steps can also be performed with IEX. The differences between these three steps are summarised in Table 1.