Impact of NaCl on Monoclonal Antibody Aggregation Induced by Agitation

Abstract

Monoclonal antibodies (mAbs) are a successful class of biotherapeutics, but their development can be challenging due to the risk of degradation that could happen at different stages of manufacturing and supply chain. One of the common causes of degradation is the agitation during transportation and clinical handling. It poses interfacial stress to the mAbs which can in turn induce protein aggregation. Moreover, the preparation of the intravenous infusion bags requires diluting the mAbs with saline solution, which could affect the extent of the agitation-induced aggregation because the level of protective surfactant is significantly reduced and salt is introduced into the mAbs solution. To better understand the complex interplay between dilution, interfacial stress and salt, we investigated the impact of sodium chloride (NaCl) on the aggregation of model antibodies from different IgG subclasses induced by agitation. We found that the presence of NaCl accelerates the aggregation for both IgG1 and IgG4 antibodies, but the aggregation mechanism, morphology, and reversibility are very different. Our results clearly highlight the impact of salt on the stability of therapeutic mAbs at the clinical in-use condition. We believe this study furthers our understanding of interfacially-mediated protein aggregation and could improve the formulation development of mAb formulations for patients.