Cation exchange (CEX) chromatography is commonly used as a polishing step in the purification of monoclonal antibodies (mAb). Purification conditions are typically optimized to run CEX chromatography in bind-and-elute mode, in which the mAb is retained on the resin while process-related contaminants, such as host cell proteins and DNA, are removed in the load or wash stages. Product-related contaminants, such as aggregates and fragments, are then removed by optimizing elution conditions to select for monomeric species. During process development activities on a new mAb product it was determined that our platform bind-and-elute mode CEX process was not capable of reducing the amount of dimer present (~2.5%) even with optimized elution conditions. While optimizing the CEX process to remove dimer species, we determined parameters that would allow us to run the CEX step in flow-through mode. Under these conditions, the amount of high molecular weight species was reduced to <1% and processing capacity was increased 7-fold. Log reduction values for process-related impurities remained comparable to levels found in bind-and-elute mode operations. In addition to improving dimer removal, running CEX in flow-through mode simplifies the CEX process, reduces resin costs, and significantly shortens processing times. Given the considerable benefits of flow-through mode operations, we have expanded the use of flow-through mode CEX to the purification of two additional mAb products in an effort to implement this as a platform process.

Development of a flow-through mode cation exchange process for the purification of a monoclonal antibody

247th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.