Reconciling predicted and measured viscosity parameters in high concentration antibody solutions

Monoclonal antibody (mAb) solution viscosity is a key developability consideration during therapeutic antibody development that should be mitigated for, with implications for downstream processing and patient safety during device-based administration. Therefore, accurate solution viscosity prediction at dose-relevant concentrations could prove key for triaging novel mAbs during early drug development campaigns where large analyte quantities required for viscosity measurements are prohibitive. Using a panel of nine anti-IL-8 IgG1 molecules and internal project assets, we demonstrate the ability of viscosity prediction and fitting models at different mAb test concentration regimes for measuring mAb viscosity-concentration profiles. For viscosity profile fitting, the modified Ross-Minton and exponential growth equations demonstrated the highest goodness of fit, but we caution against extrapolation from low concentration measurements. Moreover, use of low concentration measurements or descriptors are neither generalisable nor predictive of ultra-high concentration viscosity. Our work highlights the importance of both analyte concentration range selection, and bespoke viscosity model prediction for antibody series with the same target antigen.