Journal
JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 100, Issue 6, Pages 2071-2086Publisher
WILEY-BLACKWELL
DOI: 10.1002/jps.22432
Keywords
biotherapeutic; interferon; protein conformation; biosimilar; protein drug; structure; regulatory sciences; analytical biochemistry; physicochemical properties; oxidation
Funding
- National Institutes of Health [R01-GM070590, R01-GM086507]
- Waters Corporation
Ask authors/readers for more resources
The function, efficacy, and safety of protein biopharmaceuticals are tied to their three-dimensional structure. The analysis and verification of this higher-order structure are critical in demonstrating manufacturing consistency and in establishing the absence of structural changes in response to changes in production. It is, therefore, essential to have reliable, high-resolution and high sensitivity biophysical tools capable of interrogating protein structure and conformation. Here, we demonstrate the use of hydrogen/deuterium exchange mass spectrometry (H/DX-MS) in biopharmaceutical comparability studies. H/DX-MS measurements can be conducted with good precision, consume only picomoles of protein, interrogate nearly the entire molecule with peptide level resolution, and can be completed in a few days. Structural comparability or lack of comparability was monitored for different preparations of interferon-beta-1a. We present specific graphical formats for the display of H/DX-MS data that aid in rapidly making both the qualitative (visual) and quantitative assessment of comparability. H/DX-MS is capable of making significant contributions in biopharmaceutical characterization by providing more informative and confidant comparability assessments of protein higher-order structures than are currently available within the biopharmaceutical industry. (C) 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:2071-2086, 2011
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available