A stability screening method for predicting colloidal stability: Diffusion interaction parameter thermal shift assay

Colloidal stability is one of the most important properties to control due to the propensity for biopharmaceuticals to aggregate and the subsequent potential to severely affect the drug's efficacy and patient safety. To allow predictions of short-term and long-term colloidal stability, experiments that determine stability-indicating parameters are useful tools to aid in the selection of candidates and formulations. Using dynamic light scattering, two of the parameters that are generally applied to colloidal stability evaluation are the diffusion interaction parameter (kD) and the aggregation-onset temperature (Tonset). In this article, we describe multiplexing the kD and Tonset methods and combining them into a single light scattering method that takes repeated measurements of kD throughout a temperature ramp to determine a new parameter: the diffusion interaction parameter shift temperature (TKD). This approach eliminates difficulties with which temperature or concentration to report and reduces a large dataset down to a dingle factor, which allows for comparison and assessment of stability.