Conclusions
AEX membranes are widely used in polishing operations for the removal of residual DNA, HCP, and viruses. Current-generation
benchmarks for virus removal are >6 LRVs for MuLV and MVM at loads of up to 20 kg/L of membrane, exceeding the physical performance
limits of packed-bed resins.11,12 When there are significant amounts of residual HCP in the feed stream, resins still have a competitive edge, particularly
at high conductivities. Recent developments in the field, including the application of higher charge densities and mixed-mode
chemistries, have allowed column chromatography to address some of its limitations in flow-through applications. Membranes
provide a convective matrix that allows a much higher linear flow rate in flow-through mode, offering higher productivity
than packed-bed resins using a small disposable module, which can incorporate any surface chemistry.
In this study, we have shown that an optimized base support membrane matrix combined with a weak anion exchange chemistry
based on polyallylamine ligands provides a robust method for virus clearance at physiological conductivities and above. STIC
and traditional Q chemistry methods exhibit a clear on–off anion-exchange mechanism that can be used for the first or second
polishing step after capture. STIC does not work with polyvalent buffer systems such as phosphate buffers, but because polyvalent
buffers are not recommended for capturing offloads, this should not be a cause for concern in most processes. Although Q chromatography
may remain the workhorse in polishing, STIC allows polishing to be carried out without an interstitial dilution step, which
reduces process time and avoids additional buffer preparation and hold steps. More importantly, overall process safety is
increased because of the more efficient removal of less acidic contaminants. Studies are under way to demonstrate the removal
of HCP under different process conditions.
RENE FABER, PhD, is the director of membrane modification R&D and UWE GOTTSCHALK, PhD, is the vice president of Purification Technologies, at Sartorius Stedim Biotech GmbH, Goettingen, Germany, rene.faber@sartorius.com
Gottschalk is also a member of BioPharm International's Editorial Advisory Board. YUJING YANG, PhD, is the director of purification technologies at Sartorius Stedim North America, Bohemia, NY.
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