This article appears in a special supplement, A Renaissance in Biomanufacturing:The Art of Purification, published in August 2013.
What are the challenges to developing a reliable, robust means of performing protein purification in a single-use unit? What properties would a single-use product for protein purification need to be economically viable?
Gottschalk: Industry is changing to a ‘market-pull’ scenario, mainly due to regulatory pressure to pro-actively provide best practice. Single-use manufacturing adds value in certain downstream unit operations. While such practice has never been questioned for steps such as virus or sterile filtration, we are in the middle of that shift in chromatography and X-Flow filtration. Although it can be demonstrated that single-use strategies provide better process economies, their main advantages stem from factors such as accelerated development timelines and risk mitigation.
BioPharm: What recent developments in membrane adsorbers could lead to single-use technology for protein purification? Could membrane adsorbers replace packed-bed column chromatography?
Gottschalk: Membrane adsorbers offer two main advantages compared to packed-bed chromatography: the fluid dynamics of a convective media that can process large feed-stream volumes with extremely high flow rates, and large pore sizes that provide accessability and thus high dynamic binding capacities for large molecules such as DNA and viruses.
As a result, single-use membrane chromatography devices are typically much smaller in size and require only about 5% of the original buffer volume. The sweet spot for membrane chromatography is related to these two stand-alone features and it shines in areas like contaminant removal (polishing in flow-through mode) and purification of viral vaccines. In these applications they start dominating the industry’s development platforms and will take over from resins completely. Recent developments include salt-tolerant chemistries on membranes that bind viruses under physiological conditions (no in-process dilution requirements).
BioPharm: What technologies in development could make protein chromatography a continuous process?
Gottschalk: In general, continuous processing offers the advantage of higher productivities, from a smaller footprint to an advantageous process economy and chromatography. Technologies such as simulated moving-bed chromatography have the potential to decrease column sizes because they use the total binding capacity as well as the overall lifetime of the chromatography medium. In this setup, a single-use design is possible if, for example, the same sample of medium is recycled within the purification of just one batch of product. Although this scenario would cut costs during clinical manufacturing, it is probably less beneficial in routine manufacturing and questions of scale up remain.