Minimizing On-Column Monoclonal Antibody Aggregate Formation

By Giorgio Carta, Payal Khandelwal, and Mark Snyder

The formation of aggregates is a common occurrence during monoclonal antibody (mAb) purification and can happen for several reasons.  Aggregates are undesirable due to the possibility of altered pharmacodynamics, pharmacokinetics, and/or increased immunogenicity. Generally, the formation of aggregates is shown to be product or process related.  Here we show how on-column aggregate formulation is dependent on the resin type and on the resin's interactions with the mAb loaded.  Among the various resins tested, Nuvia™ HR-S Resin, a high-resolution cation exchanger, demonstrated the lowest proportion of on-column aggregate formation with two mAbs.  On-column aggregate formation can therefore be minimized by proper resin screening and subsequent optimization of resin type used for purification process development.