title: The utility of hydrogen/deuterium exchange mass spectrometry in biopharmaceutical comparability studies.
abstract: 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-β-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.
authors.affiliation: Biogen Idec, Inc, Cambridge, Massachusetts 02142, USA.
authors.forename: Damian
authors.initials: D
authors.lastname: Houde
authors.forename: Steven A
authors.initials: SA
authors.lastname: Berkowitz
authors.forename: John R
authors.initials: JR
authors.lastname: Engen
mesh_terms: D001702:Biopharmaceutics / Q000379:methods* / Q000592:standards; D041961:Deuterium Exchange Measurement; D007372:Interferons / Q000737:chemistry; D013058:Mass Spectrometry; D008958:Models, Molecular; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods* / Q000592:standards
chemical_list: D011506:Proteins; D007372:Interferons