Salt Tolerant Interaction Chromatography for Large-Scale Polishing with Convective Media - STIC allows polishing to be carried out without an interstitial dilution step, which reduces process time and

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Salt Tolerant Interaction Chromatography for Large-Scale Polishing with Convective Media
STIC allows polishing to be carried out without an interstitial dilution step, which reduces process time and avoids additional buffer preparation and hold steps.


BioPharm International Supplements


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,
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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