Improving Lyophilization of Recombinant Proteins with ssHDX-MS

Performance Period: 4/1/2019 to 12/31/2020

More than 40% of protein drugs approved by the FDA in the past decade are sold as solid powders. Most are produced by lyophilization, a manufacturing process that is effective but slow and inefficient. Developing or improving a lyophilization process requires stability studies to ensure product quality. In a stability study, the product is stored at controlled conditions and analyzed over time for drug degradation. Because degradation is usually slow, stability studies can take months or even years to complete. This increases time-to-market for new drugs and slows manufacturing improvements for existing drugs.

This project will evaluate a novel analytical method, called solid-state hydrogen deuterium exchange with mass spectrometric analysis (ssHDX-MS), as an alternative to stability studies for proteins in solid powders. ssHDX-MS takes just days to complete and the results are highly correlated with formulation-induced stability changes. This NIIMBL project will relate changes in lyophilization process to ssHDX-MS and protein stability on storage, testing whether ssHDX-MS can be a surrogate for stability studies. The project will also evaluate ssHDX-MS for novel drying methods being developed as alternatives to lyophilization. The ssHDX-MS method is currently TRL 4 and will be advanced to TRL 6-7 in this project.