Abstract
PurposeFilgrastim, a recombinant human granulocyte-colony stimulating factor, is widely used to treat congenital and acquired neutropenia. Following patent expiration of the innovator filgrastim product, biosimilar filgrastim products have been approved in the EU and shown to be comparable with the innovator with respect to quality, safety and efficacy. In less regulated markets, copy filgrastim products are available but data about their quality are scarce. In the present study, we provide a head-to-head comparative study on the quality of biosimilar and copy filgrastim products.MethodsInnovator filgrastim product, Neupogen®, two EU-licensed biosimilars, Zarzio® and Tevagrastim®, and two copy filgrastim products, Biocilin® and PDgrastim®, were subjected to peptide mapping, circular dichroism spectroscopy, fluorescence spectroscopy, sodium dodecyl sulfate polyacrylamide gel electrophoresis, high performance size-exclusion chromatography, reversed-phase ultra-performance liquid chromatography, endotoxin test, flow imaging microscopy and in vitro potency assay.ResultsZarzio® and Tevagrastim® have comparable quality to Neupogen®, while Biocilin® showed a significantly lower and PDgrastim® a higher specific activity. Moreover, PDgrastim® showed a higher level of impurities and a lower thermo stability than the other products.ConclusionsExcept for the deviating specific activities of the two copy filgrastim products, we found no substantial differences in product quality between the filgrastim products studied.
Highlights
Recombinant human granulocyte-colony stimulation factor is one of the first recombinant biologics that was authorized for the use in hematology [1]
The secondary and tertiary structure of selected filgrastim products were evaluated in function of their thermal stability by circular dichroism and intrinsic fluorescence spectroscopy, respectively
All products showed a positive band at 193 nm and negative bands at 208 nm and 222 nm [31], indicating they all share an alpha-helix-rich structure which has been described for filgrastim. [32,33,34]
Summary
Recombinant human granulocyte-colony stimulation factor (rhG-CSF) is one of the first recombinant biologics that was authorized for the use in hematology [1]. Two different forms of rhG-CSF are distinguished, namely filgrastim (from Escherichia coli [E. coli], under the trade name Neupogen®) and lenograstim (from Chinese hamster ovary cell, brand name Granocyte®) [2]. Filgrastim contains 175 amino acids and differs from the endogenous protein, as it lacks O-glycosylation and has an additional methionine group at the N-terminus [3]. Its use was approved in 1991 in the EU and US. A generation filgrastim is pegfilgrastim (brand name Neulasta®). Owing to the covalent attachment of 20 kDa polyethylene glycol (PEG) to the N-terminal methionyl residue of filgrastim, pegfilgrastim has extended circulating half-life, and can be administered less frequently than filgrastim [4]
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