Over 40% of FDA-approved protein drugs are sold as solid powders, mainly produced by lyophilization. This process is effective but slow. Stability studies, which ensure product quality, take months or years due to slow degradation, delaying new drug availability and manufacturing improvements.
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.
Evaluation of ssHDX-MS as a potential tool to rapidly determine the stability of lyophilized drug products during process development and formulation.
Decrease the risk of post-approval CMC changes and enable high-resolution evaluation of novel drying technologies for recombinant proteins.
For the two studied lyophilized proteins, ssHDX-MS predicted stability in ~400 hrs, vs. 12 months for a standard stability study.
ssHDX-MS was demonstrated on a protein that underwent a novel Microglassification(TM) technique as well as a spray dried formulation.
Balakrishna Chandrababu, K., Allmendinger, A., Kumar, L., Walters, B., Zarraga, I., & Topp, E. M., Effect of fill volume, protein-excipient ratio and lyo cycle on solid state hydrogen-deuterium exchange mass spectrometry (ssHDX-MS) and storage stability of a lyophilized mAb, May 25, 2022.
Balakrishna Chandrababu, K., Improving Lyophilization of Recombinant Proteins with ssHDX-MS, NIIMBL Member Forum, Virtual, October 22, 2020.
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Purdue University
Genentech, Inc.
Lindy Biosciences, Inc.
