title: Biochemical assessment of erythropoietin products from Asia versus US Epoetin alfa manufactured by Amgen.
abstract: We compared the physical and chemical properties of purported copies of recombinant human erythropoietin (rHuEPO) purchased from Korea, China, and India with the innovator product, Epoetin alfa, manufactured by Amgen Inc. The products were characterized for similarity in the types of glycoforms present, the relative degree of unfolding, in vitro potency, presence of covalent aggregates, and presence of cleavage products using established analytical methods. All products were different from Epoetin alfa (Epogen). The purported copies of rHuEPO from Korea, India, and China contained more glycoforms and other impurities. The in vitro relative potency varied for each product when based on the labeled concentration, while the concentration based on ELISA analysis brought the relative potency, for most products closer to 100%. These data emphasize potential biochemical discrepancies resulting from different cell lines and manufacturing processes. Concentrations varied within products and did not always match the information provided on the product label. As it is not possible to reliably correlate such biochemical discrepancies to clinical consequences, or the lack thereof, these data support the need for extensive preclinical testing and clinical testing of all investigational products as not all safety and efficacy aspects can be assessed during preclinical evaluation.
authors.affiliation: Amgen Inc., Process and Product Development, Formulation and Analytical Resources Group, Thousand Oaks, California 91320, USA.
authors.forename: Sungae S
authors.initials: SS
authors.lastname: Park
authors.forename: Jihea
authors.initials: J
authors.lastname: Park
authors.forename: Jason
authors.initials: J
authors.lastname: Ko
authors.forename: Louise
authors.initials: L
authors.lastname: Chen
authors.forename: David
authors.initials: D
authors.lastname: Meriage
authors.forename: Jill
authors.initials: J
authors.lastname: Crouse-Zeineddini
authors.forename: Wendy
authors.initials: W
authors.lastname: Wong
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Kerwin
mesh_terms: D001208:Asia; D001681:Biological Assay; D015153:Blotting, Western; D002681:China; D004345:Drug Industry; D019075:Electrophoresis, Capillary; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000737:chemistry* / Q000494:pharmacology / Q000592:standards*; D006397:Hematinics / Q000737:chemistry* / Q000494:pharmacology / Q000592:standards*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007194:India; D007525:Isoelectric Focusing; D007536:Isomerism; D007723:Korea; D009994:Osmolar Concentration; D011487:Protein Conformation; D011994:Recombinant Proteins; D014481:United States
chemical_list: D006397:Hematinics; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa