title: Evaluation of the structural, physicochemical, and biological characteristics of SB4, a biosimilar of etanercept.
abstract: A biosimilar is a biological medicinal product that is comparable to a reference medicinal product in terms of quality, safety, and efficacy. SB4 was developed as a biosimilar to Enbrel® (etanercept) and was approved as Benepali®, the first biosimilar of etanercept licensed in the European Union (EU). The quality assessment of SB4 was performed in accordance with the ICH comparability guideline and the biosimilar guidelines of the European Medicines Agency and Food and Drug Administration. Extensive structural, physicochemical, and biological testing was performed with state-of-the-art technologies during a side-by-side comparison of the products. Similarity of critical quality attributes (CQAs) was evaluated on the basis of tolerance intervals established from quality data obtained from more than 60 lots of EU-sourced and US-sourced etanercept. Additional quality assessment was focused on a detailed investigation of immunogenicity-related quality attributes, including hydrophobic variants, high-molecular-weight (HMW) species, N-glycolylneuraminic acid (NGNA), and α-1,3-galactose. This comprehensive characterization study demonstrated that SB4 is highly similar to the reference product, Enbrel®, in structural, physicochemical, and biological quality attributes. In addition, the levels of potential immunogenicity-related quality attributes of SB4 such as hydrophobic variants, HMW aggregates, and α-1,3-galactose were less than those of the reference product.
authors.affiliation: a Quality Evaluation Team , Samsung Bioepis , Incheon , South Korea.
authors.forename: Ick Hyun
authors.initials: IH
authors.lastname: Cho
authors.affiliation: a Quality Evaluation Team , Samsung Bioepis , Incheon , South Korea.
authors.forename: Nayoung
authors.initials: N
authors.lastname: Lee
authors.affiliation: a Quality Evaluation Team , Samsung Bioepis , Incheon , South Korea.
authors.forename: Dami
authors.initials: D
authors.lastname: Song
authors.affiliation: a Quality Evaluation Team , Samsung Bioepis , Incheon , South Korea.
authors.forename: Seong Young
authors.initials: SY
authors.lastname: Jung
authors.affiliation: b Biogen , Cambridge , MA , USA.
authors.forename: George
authors.initials: G
authors.lastname: Bou-Assaf
authors.affiliation: b Biogen , Cambridge , MA , USA.
authors.forename: Zoran
authors.initials: Z
authors.lastname: Sosic
authors.affiliation: b Biogen , Cambridge , MA , USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: b Biogen , Cambridge , MA , USA.
authors.forename: Yelena
authors.initials: Y
authors.lastname: Lyubarskaya
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000276:immunology*; D059451:Biosimilar Pharmaceuticals / Q000737:chemistry*; D016466:CHO Cells; D002152:Calorimetry, Differential Scanning; D002850:Chromatography, Gel; D003412:Cricetulus; D000068800:Etanercept / Q000737:chemistry* / Q000276:immunology*; D005062:European Union; D006031:Glycosylation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019158:N-Acetylneuraminic Acid / Q000032:analysis; D009438:Neuraminic Acids / Q000032:analysis; D010449:Peptide Mapping; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D020539:Sequence Analysis, Protein; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D059451:Biosimilar Pharmaceuticals; D009438:Neuraminic Acids; C032592:N-glycolylneuraminic acid; D019158:N-Acetylneuraminic Acid; D000068800:Etanercept
keywords: Benepali; Brenzys; Fc fusion protein; SB4; biosimilar; critical quality attribute; etanercept