title: Quality and Batch-to-Batch Consistency of Original and Biosimilar Epoetin Products.
abstract: Comprehensive physicochemical characterization and biological assays are essential parts in assessing quality attributes of biologicals. Here, we compared the quality of different marketed recombinant human erythropoietin (epoetin) products: originators, Eprex and NeoRecormon as well as 2 biosimilars, Retacrit and Binocrit. In addition, assessment of batch-to-batch variability was included by collecting 2 or more batches of each product. Common assays which included sodium dodecyl sulfate-polyacrylamide gel electrophoresis, high-performance size-exclusion chromatography, asymmetrical flow field-flow fractionation, capillary zone electrophoresis, and potency testing were used. Of the tested products and among batches of single products, variations in epoetin content, isoform profiles, and potency were found. Ultimately, this study demonstrated the high quality of epoetin products with some degree of variation among products and batches, confirming the "similar but not identical" paradigm of biologicals.
authors: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, 3584 CG Utrecht, the Netherlands.
authors: Liem Andhyk
authors: LA
authors: Halim
authors: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, 3584 CG Utrecht, the Netherlands.
authors: Vera
authors: V
authors: Brinks
authors: Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research, Leiden University, 2300 RA Leiden, the Netherlands.
authors: Wim
authors: W
authors: Jiskoot
authors: Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research, Leiden University, 2300 RA Leiden, the Netherlands.
authors: Stefan
authors: S
authors: Romeijn
authors: Division of BioAnalytical Chemistry, AIMMS research group BioMolecular Analysis, VU University Amsterdam, 1081 HV Amsterdam, the Netherlands.
authors: Rob
authors: R
authors: Haselberg
authors: Biotherapeutics Group, National Institute for Biological Standards and Control, Hertfordshire, EN6 3QG, UK.
authors: Chris
authors: C
authors: Burns
authors: Biotherapeutics Group, National Institute for Biological Standards and Control, Hertfordshire, EN6 3QG, UK.
authors: Meenu
authors: M
authors: Wadhwa
authors: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, 3584 CG Utrecht, the Netherlands. Electronic address: h.schellekens@uu.nl.
authors: Huub
authors: H
authors: Schellekens
mesh_terms: D000818:Animals; D059451:Biosimilar Pharmaceuticals / Q000032:analysis / Q000737:chemistry / Q000592:standards*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D000068817:Epoetin Alfa / Q000032:analysis / Q000737:chemistry / Q000592:standards*; D004921:Erythropoietin / Q000032:analysis / Q000737:chemistry / Q000592:standards*; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000032:analysis / Q000737:chemistry / Q000592:standards; D013810:Therapeutic Equivalency
chemical_list: D059451:Biosimilar Pharmaceuticals; D011994:Recombinant Proteins; C103998:epoetin beta; C530192:epoetin zeta; D004921:Erythropoietin; D000068817:Epoetin Alfa
keywords: biosimilar; immunogenicity; physicochemical properties; protein characterization; recombinant human erythropoietin