Monthly Publication Highlight - Dr. Elizabeth Topp
The Purdue College of Pharmacy is pleased to honor and recognize the outstanding research and scholarship generated by our faculty each month. This month we highlight Dr. Elizabeth Topp, Professor of Industrial and
Physical Pharmacy. Dr. Topp’s recent publication, “Effects of Drying Process on an IgG1 Monoclonal Antibody Using Solid-State Hydrogen Deuterium Exchange with Mass Spectrometric Analysis (ssHDX-MS)”, can be read in Pharmaceutical Research (January, 2018; DOI: 10.1007/s11095-017-2318-9). The study was conducted in collaboration with former graduate student, Ehab Moussa, current graduate student, Nathan Wilson, assistant professor, Tony Zhou and Pfizer collaborators, Satish Sign and Sandeep Nema.
Protein drugs are an increasingly important part of the pharmaceutical industry. Though usually administered by injecting a solution, many protein drugs are sold as dried powders that have to be reconstituted (dissolved) before they can be given to patients. These dried powder formulations are used because the protein is unstable in solution, and are produced by processes such as lyophilization (freeze-drying) or spray drying. A challenge in developing these dried powders is that very few analytical methods can “see” the protein in the solid state. As a result, the formulations and drying processes that produce them are developed largely by trial-and-error, a time consuming and expensive approach.
Over the past ten years, Dr. Topp and her group have developed solid-state hydrogen deuterium exchange with mass spectrometric analysis (ssHDX-MS) as a novel analytical method to “see” proteins in the solid state. This paper examines the effect of several drying processes on ssHDX-MS for a monoclonal antibody (mAb). MAbs are the largest class of protein drugs, and include clinically and commercially important products such as Herceptin® and Humira®. The paper shows that ssHDX-MS can detect differences in mAbs in solid powders produced by different methods. For example, powders that were produced by spray drying showed an ssHDX-MS pattern consistent with two populations of mAb molecules, while powders produced by lyophilization showed only one population.
“I’m excited about these results because they suggest that ssHDX-MS can be used to support innovations in manufacturing. Currently, any changes in manufacturing processes must be validated using stability studies, which can take months or years to complete. The results reported here, and other work from my lab, suggests that ssHDX-MS can provide comparable information in a couple of weeks.”