Evaluation of Two Novel Scale-Down Devices for Testing Monoclonal Antibody Aggregation During Large-Scale Freezing.

There is a need for representative small volume devices that reflect monoclonal antibody (mAb) aggregation during freezing and thawing (FT) in large containers. We characterised two novel devices that aim to mimic the stress in rectangular 2 L bottles. The first scale-down device (SDD) consists of a 125 mL bottle surrounded by a 3D printed cover that manipulates heat exchange. The second device, a micro scale-down device (mSDD), adapts cooling and heating of 10 mL vials to extend stress time. MAb aggregation upon repeated FT was evaluated considering formation of higher molecular weight species, subvisible particles, and the increase in hydrodynamic radius, polydispersity index, and optical density at 350 nm. Three different mAb solutions were processed. Both an unshielded 125 mL bottle and the SDD can be used to predict aggregation during FT in 2 L bottles. In specific cases the unshielded 125 mL bottle underestimates whereas the SDD slightly overestimates soluble aggregate formation. The mSDD increases aggregation compared to 10 mL vials but is less representative than the SDD. Ultimately, both SDDs enable characterisation of protein sensitivity to large-scale FT with two orders of magnitude less volume and are superior to simply using smaller bottles.