title: Forced degradation of therapeutic proteins.
abstract: The scope of this paper is to review approaches used for forced degradation (synonym, stress testing) of therapeutic proteins. Forced degradation studies play a central role in the development of therapeutic proteins, for example, for candidate selection, molecule characterization, formulation development, assay development, and comparability studies. Typical stress methods are addressed within this review, such as exposure to elevated temperatures, freeze-thawing, mechanical stress, oxidation, light, as well as various materials and devices used in the clinics during final administration. Stability testing is briefly described as far as relevant to the discussion of forced degradation studies. Whereas stability-testing requirements are defined in regulatory guidelines, standard procedures for forced degradation of therapeutic proteins are largely unavailable, except for photostability. Possible selection criteria to identify appropriate stress conditions and recommendations for setting up forced degradation studies for the different phases of development of therapeutic proteins are presented.
authors.affiliation: Division of Drug Delivery Technology, Leiden/Amsterdam Center for Drug Research, 2300 RA Leiden, The Netherlands.
authors.forename: Andrea
authors.initials: A
authors.lastname: Hawe
authors.forename: Michael
authors.initials: M
authors.lastname: Wiggenhorn
authors.forename: Marco
authors.initials: M
authors.lastname: van de Weert
authors.forename: Joerg H O
authors.initials: JH
authors.lastname: Garbe
authors.forename: Hanns-Christian
authors.initials: HC
authors.lastname: Mahler
authors.forename: Wim
authors.initials: W
authors.lastname: Jiskoot
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D004355:Drug Stability; D010084:Oxidation-Reduction; D011487:Protein Conformation; D055550:Protein Stability; D011506:Proteins / Q000737:chemistry* / Q000627:therapeutic use; D013314:Stress, Mechanical; D013696:Temperature
chemical_list: D011506:Proteins