In biologic drug product development, formulation conditions can overcome both physical and chemical stability challenges, as well as modulate viscosity. Stabilizing excipients in protein formulations may function in mechanistically different ways; certain excipients may modify the properties of bulk solution (e.g., decrease viscosity or form networks of non-covalent bonds), while others function via specific and/or non-specific interactions with the protein surface. Here, we developed a high-throughput, on-column excipient screening method to explore the mechanistic basis of excipient stabilization and interaction of various excipients with a model protein.<br/>Protein was conjugated to an inert resin and packed into a column. The column was attached to an HPLC system with UV detection, and excipients were injected. The observed differences in elution time were compared to both a control column (not conjugated to protein) and to a non-interacting neutral flow marker. Injections of each excipient were made in the presence of mobile phases with various pH and ionic strength conditions to drive the mechanistic understanding of the observed interactions. Complementary methods were used to cross-validate the observed interactions, and calorimetry and fluorimetry were used to understand their impact on thermal stability. In particular, NMR diffusion studies provide insight into the level of interaction between the protein and each excipient. An understanding of how an excipient stabilizes a protein formulation will help design better drug products and allow QbD process development. Development of this high throughput on-column excipient screening method will allow formulators to easily screen for interactions that can impact protein stability using minimal protein material, expanding our toolkit for formulation development.

Exploring protein-excipient interactions via on-column screening and complementary methods

253rd National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.