A Novel Thermodynamic Assay For Predicting And Monitoring Biomolecular Structure Stability

Perturbations in the structure of large biomolecules result in concomitant changes in biomolecular function. Biological molecules require stabilization for in vitro analysis, extended storage, manufacturing, and processing. Changes in the structure of biotherapeutic molecules could unexpectedly reduce or enhance the quality and safety of a drug product. The primary stabilizing forces for biomolecules in solution are the non-covalent interactions between the biomolecule and its immediate solution environment. In living organisms, biomolecules are stabilized through a network of active cellular processes. In solution, biomolecules rely on excipients for stabilization.

Analytical instruments that can quantify the chemical influence of excipients on the structural stability of a biomolecule include spectroscopic, scattering, fluorescence, and thermodynamic techniques. Since samples do not require labeling or modification, thermodynamic techniques are sensitive, reproducible, and easy to setup.

Explore results from a comparability study of a liquid protein reference formulation that utilized a nano differential scanning calorimeter to detect changes in biomolecular structure in response to subtle manipulations in the reference formulation.