title: Drifts in ADCC-related quality attributes of Herceptin®: Impact on development of a trastuzumab biosimilar.
abstract: A biosimilar product needs to demonstrate biosimilarity to the originator reference product, and the quality profile of the latter should be monitored throughout the period of the biosimilar's development to match the quality attributes of the 2 products that relate to efficacy and safety. For the development of a biosimilar version of trastuzumab, the reference product, Herceptin®, was extensively characterized for the main physicochemical and biologic properties by standard or state-of-the-art analytical methods, using multiple lots expiring between March 2015 and December 2019. For lots with expiry dates up to July 2018, a high degree of consistency was observed for all the tested properties. However, among the lots expiring in August 2018 or later, a downward drift was observed in %afucose (G0+G1+G2). Furthermore, the upward drift of %high mannose (M5+M6) was observed in the lots with expiry dates from June 2019 to December 2019. As a result, the combination of %afucose and %high mannose showed 2 marked drifts in the lots with expiry dates from August 2018 to December 2019, which was supported by the similar trend of biologic data, such as FcγRIIIa binding and antibody-dependent cell-mediated cytotoxicity (ADCC) activity. Considering that ADCC is one of the clinically relevant mechanisms of action for trastuzumab, the levels of %afucose and %high mannose should be tightly monitored as critical quality attributes for biosimilar development of trastuzumab.
authors.affiliation: a Quality Evaluation Team, Samsung Bioepis , Incheon , South Korea.
authors.forename: Seokkyun
authors.initials: S
authors.lastname: Kim
authors.affiliation: a Quality Evaluation Team, Samsung Bioepis , Incheon , South Korea.
authors.forename: Jinsu
authors.initials: J
authors.lastname: Song
authors.affiliation: a Quality Evaluation Team, Samsung Bioepis , Incheon , South Korea.
authors.forename: Seungkyu
authors.initials: S
authors.lastname: Park
authors.affiliation: a Quality Evaluation Team, Samsung Bioepis , Incheon , South Korea.
authors.forename: Sunyoung
authors.initials: S
authors.lastname: Ham
authors.affiliation: a Quality Evaluation Team, Samsung Bioepis , Incheon , South Korea.
authors.forename: Kyungyeol
authors.initials: K
authors.lastname: Paek
authors.affiliation: a Quality Evaluation Team, Samsung Bioepis , Incheon , South Korea.
authors.forename: Minjung
authors.initials: M
authors.lastname: Kang
authors.affiliation: a Quality Evaluation Team, Samsung Bioepis , Incheon , South Korea.
authors.forename: Yunjung
authors.initials: Y
authors.lastname: Chae
authors.affiliation: a Quality Evaluation Team, Samsung Bioepis , Incheon , South Korea.
authors.forename: Heewon
authors.initials: H
authors.lastname: Seo
authors.affiliation: a Quality Evaluation Team, Samsung Bioepis , Incheon , South Korea.
authors.forename: Hyung-Chan
authors.initials: HC
authors.lastname: Kim
authors.affiliation: a Quality Evaluation Team, Samsung Bioepis , Incheon , South Korea.
authors.forename: Michael
authors.initials: M
authors.lastname: Flores
mesh_terms: D000920:Antibody-Dependent Cell Cytotoxicity; D059451:Biosimilar Pharmaceuticals / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D006801:Humans; D011786:Quality Control; D000068878:Trastuzumab / Q000737:chemistry / Q000494:pharmacology
chemical_list: D059451:Biosimilar Pharmaceuticals; D000068878:Trastuzumab
keywords: ADCC; FcγRIIIa; Herceptin®; N-glycan; biosimilar; quality drift; trastuzumab