title: A Retrospective Evaluation of the Use of Mass Spectrometry in FDA Biologics License Applications.
abstract: The characterization sections of biologics license applications (BLAs) approved by the United States Food and Drug Administration (FDA) between 2000 and 2015 were investigated to examine the extent of the use of mass spectrometry. Mass spectrometry was found to be integral to the characterization of these biotherapeutics. Of the 80 electronically submitted monoclonal antibody and protein biotherapeutic BLAs included in this study, 79 were found to use mass spectrometric workflows for protein or impurity characterization. To further examine how MS is being used in successful BLAs, the applications were filtered based on the type and number of quality attributes characterized, the mass spectrometric workflows used (peptide mapping, intact mass analysis, and cleaved glycan analysis), the methods used to introduce the proteins into the gas phase (ESI, MALDI, or LC-ESI), and the specific types of instrumentation used. Analyses were conducted over a time course based on the FDA BLA approval to determine if any trends in utilization could be observed over time. Additionally, the different classes of protein-based biotherapeutics among the approved BLAs were clustered to determine if any trends could be attributed to the specific type of biotherapeutic. Graphical Abstract ᅟ.
authors.affiliation: Division of Pharmaceutical Analysis, Office of Testing and Research, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, 20993, USA. Sarah.Rogstad@fda.hhs.gov.
authors.forename: Sarah
authors.initials: S
authors.lastname: Rogstad
authors.affiliation: Division of Pharmaceutical Analysis, Office of Testing and Research, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, 20993, USA.
authors.forename: Anneliese
authors.initials: A
authors.lastname: Faustino
authors.affiliation: Biotechlogic, Inc., Glenview, IL, 60025, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Ruth
authors.affiliation: Division of Pharmaceutical Analysis, Office of Testing and Research, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, 20993, USA.
authors.forename: David
authors.initials: D
authors.lastname: Keire
authors.affiliation: Biotechlogic, Inc., Glenview, IL, 60025, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Boyne
authors.affiliation: Office of Biotechnology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, 20993, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Park
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry*; D001688:Biological Products / Q000737:chemistry*; D017277:Drug Approval / Q000379:methods*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D010449:Peptide Mapping / Q000379:methods; D014481:United States; D014486:United States Food and Drug Administration; D057188:Workflow
chemical_list: D000911:Antibodies, Monoclonal; D001688:Biological Products
keywords: Mass spectrometry; Monoclonal antibodies; Protein therapeutics