title: Charge Variants of an Avastin Biosimilar Isolation, Characterization, In Vitro Properties and Pharmacokinetics in Rat.
abstract: The similarity between a proposed biosimilar product and the reference product can be affected by many factors. This study is designed to examine whether any subtle difference in the distribution of the charge variants of an Avastin biosimilar can affect its in vitro potency and in vivo PK. Here, the acidic, basic and main peak fractions of a biosimilar product were isolated using high-performance cation-exchange chromatography and were subjected to various studies to compare their in vitro properties and in vivo PK profile. A serial of analytical methods, including size exclusion chromatography (SEC), imaged capillary isoelectric focusing (icIEF) capillary zone electrophoresis (CZE) and cation-exchange chromatography (CEX-HPLC) were also used to characterize the isolated charge variants. The kinetics constant was measured using a Biacore X100 system. The study indicates the biosimilar product has a high similarity with avastin in physicochemical properties. The potency in vitro and PK profile in rat of charge variants and biosimilar product are consistent with avastin.
authors.affiliation: School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, 264005, P.R. China.|State Key Laboratory of Long-acting and Targeting Drug Delivery System, Luye Pharma Group Ltd., Yantai, 264005, P.R. China.
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Zhao
authors.affiliation: School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, 264005, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, 264005, P.R. China.|State Key Laboratory of Long-acting and Targeting Drug Delivery System, Luye Pharma Group Ltd., Yantai, 264005, P.R. China.
authors.forename: Wan-Hui
authors.initials: WH
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Long-acting and Targeting Drug Delivery System, Luye Pharma Group Ltd., Yantai, 264005, P.R. China.
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Tao
authors.affiliation: State Key Laboratory of Long-acting and Targeting Drug Delivery System, Luye Pharma Group Ltd., Yantai, 264005, P.R. China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Long-acting and Targeting Drug Delivery System, Luye Pharma Group Ltd., Yantai, 264005, P.R. China.
authors.forename: Zhen-Duo
authors.initials: ZD
authors.lastname: Shen
mesh_terms: D000818:Animals; D000068258:Bevacizumab / Q000493:pharmacokinetics*; D059451:Biosimilar Pharmaceuticals / Q000493:pharmacokinetics*; D049109:Cell Proliferation / Q000187:drug effects*; D002852:Chromatography, Ion Exchange; D019075:Electrophoresis, Capillary; D061307:Human Umbilical Vein Endothelial Cells; D007525:Isoelectric Focusing; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D059451:Biosimilar Pharmaceuticals; D000068258:Bevacizumab