Wednesday, October 16 12h00 MSG025 Bernal Institute

Solid-state Hydrogen Deuterium Exchange (ssHDX-MS) in the Development of Lyophilized Protein Formulations


Many protein drugs are marketed as lyophilized solid powders. To develop the product, candidate formulations are evaluated in stability studies that can take years to complete. While physicochemical analyses (e.g. FTIR, Tg) provide information about the properties of the solid, they are usually poorly correlated with storage stability. There is a need for a stability-indicating analytical method for proteins in Iyophilized powders and other amorphous solids.

The Topp group has developed solid-state hydrogen deuterium exchange with mass spectrometric analysis (ssHDX-MS) as a novel analytical method for proteins in lyophilized solids, providing high resolution information on protein structure and matrix interactions. The group has shown that ssHDX-MS is sensitive to changes in formulation, moisture content and processing method. ssHDX-MS has also been shown to be highly correlated with the storage stability of various formulations of myoglobin (Mb) and of a monoclonal antibody (mAb). ssHDX-MS thus shows promise as a stability-indicating method that could help accelerate the development of Iyophilized protein drugs.

This presentation will provide an overview of the ssHDX-MS method and summarize results demonstrating correlation of ssHDX-MS metrics with the storage stability of several lyophilized proteins. Ongoing studies, directed toward establishing a mechanistic model for ssHDX-MS, will also be presented.


Elizabeth M. Topp is a Professor in the Department of Industrial and Physical Pharmacy at Purdue University in West Lafayette, Indiana. She received a bachelor’s degree in chemical engineering from the University of Delaware (B. Ch. E.), a master’s in chemical and biochemical engineering from the University of Pennsylvania (M.E.) and a Ph. D. in pharmaceutics from the University of Michigan. Her research addresses the chemical and physical stability of protein drugs, with particular emphasis on Iyophilized solids. She is a Fellow of the American Association of Pharmaceutical Scientists and a former Associate Editor of the Journal of Pharmaceutical Sciences. With Dr Alina Alexeenko of Purdue’s School of Aeronautics and Astronautics, she co-directs LyoHUB, an industry-led consortium to advance lyophilization technology.


Tea/coffee will be available at 11h45

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