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Differentiating the Effects of Oxidative Stress Tests on Biopharmaceuticals

Authors
  • Heinzl, Geoffrey A.1
  • Lai, Lo1
  • Rao, V. Ashutosh1
  • 1 Center for Drug Evaluation and Research, Food and Drug Administration, Laboratory of Applied Biochemistry, Division of Biotechnology Research and Review III, Office of Biotechnology Products, Office of Pharmaceutical Quality, Silver Spring, Maryland, 20993, USA , Silver Spring (United States)
Type
Published Article
Journal
Pharmaceutical Research
Publisher
Springer-Verlag
Publication Date
May 17, 2019
Volume
36
Issue
7
Identifiers
DOI: 10.1007/s11095-019-2627-2
Source
Springer Nature
Keywords
License
Yellow

Abstract

PurposeA rapid and broadly applicable method to assess relevant oxidative damage in biopharmaceuticals is important for lifecycle management of product quality. Multiple methods are currently employed as stress tests to induce oxidative damage for assessment of stability, safety, and efficacy. We compared two common methods for inducing oxidative damage to assess differences in impact on bioactivity and structure of the biopharmaceuticals.MethodsBiopharmaceuticals were treated with either metal-catalyzed oxidation (MCO) conditions or the reactive-oxygen species (ROS) inducer 2,2′-Azobis(2-amidinopropane) dihydrochloride (AAPH), then analyzed for changes in structure and bioactivity.ResultsWe demonstrate that commonly used chemical methods for assessing oxidation yield distinct oxidation profiles for each of the biotechnology products analyzed, including monoclonal antibodies. We further report oxidant- and product-specific changes in bioactivity under oxidizing conditions, along with differential oxidation on the molecular subunits of monoclonal antibodies.ConclusionOur results highlight the need for product-specific optimization and selection of orthogonal, relevant oxidizers when characterizing stress responses in biopharmaceuticals.

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