Assessing subvisible particle risks in monoclonal antibodies: insights from quartz crystal microbalance with...

Throughout the lifecycle of biopharmaceutical development and manufacturing, monoclonal antibodies (mAbs) are subjected to diverse interfacial stresses and encounter various container surfaces. These interactions can cause the formation of subvisible particles (SVPs) that complicate developability and stability assessments of the drug products. This study leverages quartz crystal microbalance with dissipation (QCM-D), an interfacial characterization technique, as well as both in silico and experimentally measured physicochemical properties, to investigate the significant differences in SVP formation among different mAbs due to interfacial stresses. We conducted forced degradation experiments in borosilicate glass and high-density polyethylene containers, using agitation and stirring to rank 15 mAbs on SVP risks. Our data indicate that the kinetics of antibody adsorption to solid-liquid interfaces correlate strongly with SVP propensity in the stirring study yet show a weaker correlation with agitation-induced SVPs. In addition, SVP morphology was analyzed using self-supervised machine learning on flow imaging microscopy images. Despite the differing surface chemistry of the two container types, stirring resulted in similar SVP morphologies, in contrast to the unique morphologies produced by agitation. Collectively, our research demonstrates the utility of QCM-D and in silico models in evaluating mAb developability and their tendency to form interface-mediated SVPs, providing a strategy to mitigate risks associated with SVP formation in biotherapeutic development.