title: Comparability of biosimilar filgrastim with originator filgrastim: protein characterization, pharmacodynamics, and pharmacokinetics.
abstract: BACKGROUND
  Biosimilars provide safety, purity, and potency similar to those of a reference biologic product.
  
  
  METHODS
  An array of protein analytical techniques was used to compare the physicochemical properties of proposed biosimilar filgrastim (EP2006), US-approved originator filgrastim, and EU-approved originator filgrastim. Biological characterization involved surface plasmon resonance spectroscopy analyses and in vitro proliferation assays. A randomized, double-blind, two-way crossover, phase I study in healthy volunteers assessed the pharmacodynamics, pharmacokinetics, and safety profiles of EP2006 and US-approved originator filgrastim (administered as a single subcutaneous 10 µg/kg injection).
  
  
  RESULTS
  EP2006 and originator filgrastim (US and EU approved) were highly similar with respect to primary, secondary, and tertiary protein structures; mass, size, purity, charge, and hydrophobicity. No differences in receptor binding affinity were observed, and all samples demonstrated similar in vitro bioactivity. In the phase I study, no statistically significant differences between EP2006 and US-approved originator filgrastim were noted in pharmacodynamic or pharmacokinetic parameters, and all confidence intervals were within the equivalence boundaries. The two products had similar safety profiles.
  
  
  CONCLUSIONS
  These studies provide robust evidence of the structural and functional similarity between the proposed biosimilar filgrastim (EP2006) and the US-approved originator filgrastim.
authors.affiliation: IBMP-Institute for Biomedical and Pharmaceutical Research, Paul-Ehrlich-Strasse 19, 90562, Nürnberg-Heroldsberg, Germany, fritz.soergel@ibmp.net.
authors.forename: Fritz
authors.initials: F
authors.lastname: Sörgel
authors.forename: Arnd
authors.initials: A
authors.lastname: Schwebig
authors.forename: Johann
authors.initials: J
authors.lastname: Holzmann
authors.forename: Stefan
authors.initials: S
authors.lastname: Prasch
authors.forename: Pritibha
authors.initials: P
authors.lastname: Singh
authors.forename: Martina
authors.initials: M
authors.lastname: Kinzig
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D059451:Biosimilar Pharmaceuticals / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002452:Cell Count; D018592:Cross-Over Studies; D004311:Double-Blind Method; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006801:Humans; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D055815:Young Adult
chemical_list: D059451:Biosimilar Pharmaceuticals; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000069585:Filgrastim
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