The Formulation and Stability research group is led by Dr Elizabeth Topp and focuses on the study of mRNA and protein-based drugs and their degradation mechanisms. The projects currently being carried out include the development of analytical methods for the characterisation of degradation products of biopharmaceutical formulations and the study of strategies to enhance the stability of these drugs. These projects are funded by a mix of collaborations with companies within the biopharma ecosystem and government initiatives (e.g. Science Foundation Ireland grants).
Caio Henrique Barros
Arda Deniz Tugrul
Formulation and Stability Group Team
Chief Scientific Officer - Formulation and Stability Group
Dr. Topp holds a bachelor’s degree in chemical engineering (BChE) from the University of Delaware, a master’s degree in engineering (ME) from the University of Pennsylvania and a PhD in pharmaceutics from the University of Michigan. She began her academic career in the Department of Pharmaceutical Chemistry at the University of Kansas in Lawrence, Kansas. In 2009, she accepted an appointment as the Dane O. Kildsig Chair and Head of the Department of Industrial and Physical Pharmacy at Purdue University in West Lafayette, Indiana, a position she held until 2017. In 2019, Dr. Topp was appointed Chief Scientific Officer at NIBRT, maintaining her Purdue faculty appointment.
Dr. Topp’s research focuses on the formulation and stability of protein drugs, with an emphasis on peptides and proteins in the amorphous solid state. This fascinating but poorly-understood state of matter challenges conventional, “solution-state” understanding of the factors that control protein structure and reactivity. The work is also of practical importance, since many protein drugs are stored and/or marketed as amorphous solids. Dr. Topp and her group have adapted analytical methods, originally developed for proteins in biological systems, to protein drug formulations. They have developed solid-state hydrogen deuterium exchange with mass spectrometric analysis (ssHDX-MS) and solid-state photolytic labeling with mass spectrometric analysis (ssPLL-MS) to probe the environment of proteins in amorphous solids with high resolution. They have shown that ssHDX-MS results are highly correlated with storage stability for several model proteins. As a result, the method is increasingly being transferred to the industry, tested in the industrial setting and adopted to accelerate formulation and process development.
An outgrowth of the Topp lab’s interest in protein stability has been the development of novel phosphorylated derivatives of glucagon (“phosphoglucagons”) that inhibit fibrillation and improve solubility and stability. The compounds have been optioned by Monon Bioventures (https://mononbioventures.com/) for preclinical development with support from an NIH FastTrack small business grant (SBIR).
Dr. Topp is the Co-Founder and Co-Director of LyoHUB, an industry-led consortium dedicated to advancing lyophilization technologies (see www.lyohub.org). LyoHUB was founded in 2014 by Dr. Topp and Dr. Alina Alexeenko of Purdue’s College of Engineering. With initial support from the National Institute of Standard’s and Technology (NIST), LyoHUB has grown to more than twenty member companies spanning the lyophilization value chain. LyoHUB maintains a pilot scale Demonstration Facility in Purdue’s Discovery Park and hosts computational tools for lyophilization on its website. Current activities of LyoHUB include writing and disseminating “best practices papers”, generating recognized consensus standards in lyophilization through the American Society for Testing and Materials (ASTM), and providing on-site and online training in lyophilization.
Dr. Topp’s contributions have been recognized with a number of awards, including induction into Purdue’s Innovator Hall of Fame, the Chaney Faculty Scholar Award of Purdue’s College of Pharmacy, and the Michael J. Pikal NIPTE Distinguished Scholar Award in Pharmaceutical Processing. She Co-Chaired the 2019 Gordon Conference on Form and Formulation for Drug Discovery and is a member of the editorial advisory board of Molecular Pharmaceutics. She is a Fellow of the American Association of Pharmaceutical Scientists (AAPS).
Dr. Topp’s research focuses on the formulation and stability of protein drugs, with an emphasis on peptides and proteins in the amorphous solid state. Her work has been funded by the National Institutes of Health (U.S.), the National Science Foundation (U.S.), the National Institute of Standards and Technology (U.S.), the Food and Drug Administration (U.S.), the Juvenile Diabetes Research Foundation, and by various pharmaceutical and biopharmaceutical companies.
Dr. Topp’s research focuses on the formulation and stability of protein and mRNA drugs, with an emphasis on formulations in the amorphous solid state. Her work has been funded by the National Institutes of Health (U.S.), the National Science Foundation (U.S.), the National Institute of Standards and Technology (U.S.), the Food and Drug Administration (U.S.), the Juvenile Diabetes Research Foundation, Science Foundation Ireland (SFI) and by various pharmaceutical and biopharmaceutical companies.
Projects and Research Areas
- Kinetics and mechanisms of solid-state hydrogen deuterium exchange (ssHDX). Effects of temperature, excipients, protein structure, pre-lyophilization pH.
- Study of degradation pathways of mRNA in formulations
- Development of analytical methods for assessment of mRNA degradation
- Protein modifications for enhancement of stability
Purdue Webpage: https://www.ipph.purdue.edu/faculty/topp
Learn more about Prof Topp's group’s pioneering work on fibrillation-resistant peptide drugs here