A common issue observed for the capture of monoclonal antibodies (mAbs) with protein A resin is the transient generation of high turbidity during product elution. This turbidity is historically attributed to acid induced precipitation of pH sensitive molecules, process-related impurities (e.g. HCP and/or DNA), or liquid-liquid phase separation. The high turbidity can lead to challenges with increased system pressure during elution caused by poor in-line eluate filter capacity. Alternatively, eliminating the in-line eluate filter and instead filtering a pooled protein A eluate might require an additional intermediate vessel and might raise concerns about bioburden control of the process intermediates. In this study, we explored using a low pH wash prior to elution to effectively reduce the turbidity seen in the eluate while maintaining an acceptably high yield. We also investigate the impact of the protein A wash options on product turbidity during the subsequent low pH viral inactivation step. The protein A pH transition wash has a positive result in reducing turbidity during elution and during the viral inactivation step. These results provide insight into implementing a strategy that enables in-line filtration for protein A chromatography and improves filterability during viral inactivation. The overall outcome is a more consistent and predictable large scale manufacturing performance.<br/>

Effect of low pH transition wash on protein A eluate-mitigation strategy to improve manufacturing filterability

255th National Meeting (2018)

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