Use of multi-column capture chromatography has been demonstrated to offer significant advantages over traditional batch chromatography in regards to improvement in productivity and capacity utilization of the resin. In our recent study, we have compared several multi-column formats (2-column, 4-column and 6-column) and the impact of process parameters such as resin type, feed titer, feed flow rates, % breakthrough and process duration on optimal performance during continuous capture. Upon identifying the optimal conditions, we have successfully demonstrated scalability of the process to a pilot-scale and purified 500L of cell culture harvest using 1.6 L of Protein-A resin. However, for this process to be successfully implemented in a clinical/commercial manufacturing setting, successful viral clearance validation is essential. In this study, we have conducted viral validation studies under cGLP guideline setting to assess viral clearance across continuous capture chromatography. Specifically, we have assessed the clearance of both enveloped and non-enveloped viruses across continuous capture chromatography in each of the three phases of continuous chromatography i.e. a) Start-up b) Steady State and c) Shut-Down. Further, we have evaluated a scale-down model using standard chromatographic operation based on valve switching to mimic the steady state operations using a continuous chromatography skid. Results from these studies are compared against viral clearance achieved by standard batch capture chromatography operated at 1% breakthrough. Finally, we have also assessed the resin cleaning strategy during continuous chromatography and assessed its impact on impurity carry over including HCPs, DNA, rPA and Viruses. As executed for continuous chromatography, a scale-down model has been developed to assess the virus carry-over as well. Together, these results show that cGLP viral validation studies can be successfully executed using continuous chromatography and a scale-down model can be successfully generated using standard chromatographic skids. Further insights will be shared on viral clearance across start-up, steady state and shut-down phases as well as effective cleaning strategies to prevent virus carry over between cyclic operations.<br/>

Viral clearance validation across continuous capture chromatography

255th National Meeting (2018)

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