Effective Protein A column regeneration is important in therapeutic monoclonal antibody (mAb) production for product quality and process economics. To design a robust and effective regeneration strategy, resin compatibility, microbial inactivation efficiency and cleaning effectiveness are three major considerations. Regenerating Protein A column using acidic (e.g. acetic acid) and/or caustic (e.g. NaOH) solutions is a common approach. However, it is challenging to balance between resin performance decline and adequate microbial control in choosing the right caustic solution concentration, even for resin with enhanced caustic tolerance such as MabSelect SuRe. This report introduces an enhanced regeneration strategy for MabSelect SuRe resin. The approach applies benzyl alcohol in low concentration acetic acid and NaOH (100 mM) solutions in sequential steps to regenerate MabSelect SuRe resin for reuse. Such solutions demonstrated good resin compatibility in resin functional test after extended solution incubation time, and demonstrated superior microbial control using eight test microorganisms. The cleaning effectiveness of the proposed strategy is demonstrated by carryover study, where product and impurity carryover was below detection limit. Finally, during a resin lifetime study, consistent step yields and product quality attributes were demonstrated, and no carryover was observed, up to 150 purification cycles. A viral clearance study further demonstrated that aged resin at the end of the resin lifetime had comparable viral clearance performance compared to new resin. No active virus was detected in the elution pool of the subsequent blank runs. These studies further verified the robustness of the proposed regeneration strategy for MabSelect SuRe resin.
Keywords: Cleaning in Place; MabSelect SuRe; Microbial inactivation; Regeneration; Resin lifetime; Sanitization in Place.
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