Early Stage Self-Association Assessments With Dynamic Light Scattering Prevent Viscosity And Aggregation Failures In Clinical Stages

By Philipp Schramm, Silvia Würtenberger, Christian Kleusch, and Stefanie Kall

Dynamic light scattering (DLS) measurements provide biophysical insights about your biologic therapeutics. One attribute measured with DLS during early-stage development is the self-association parameter (kD), which predicts the likelihood a candidate molecule will interact with itself as concentration increases.

This is a measure of whether a biologic therapeutic is likely to become prohibitively viscous for administration, or is likely to aggregate at the high concentrations required for storage. Early discovery and formulation researchers in the biologics space profile many biophysical parameters to assess a full range of quality attributes. However, they often have limited sample, and require methodologies that minimize consumption by using low sample volumes at low concentrations. The drawback is that once the candidate moves to clinical stages, it must be stored and administered at much higher concentrations. Many early-stage discovery and formulation assessments miss potential issues with viscosity or concentration-dependent aggregation.

Nonetheless, there are risk mitigation strategies applicable during early development that are predictive of these downstream issues while still avoiding high sample consumption. Read how to use DLS to help predict the self-interaction propensity of a biologic, enabling selection of optimal buffers and constructs for further development.