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BioDrugs
Published in: BioDrugs 3/2016

01-06-2016 | Original Research Article

Identification of Low-Level Product-Related Variants in Filgrastim Products Presently Available in Highly Regulated Markets

Authors: Anna Hausberger, William C. Lamanna, Martin Hartinger, Andreas Seidl, Hansjoerg Toll, Johann Holzmann

Published in: BioDrugs | Issue 3/2016

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Abstract

Background

Filgrastim is a recombinant, non-glycosylated form of human granulocyte colony-stimulating factor, used to stimulate leukocyte proliferation in patients suffering from neutropenia. Since the expiration of patents associated with Amgen’s filgrastim biopharmaceutical, Neupogen®, in 2006, a number of filgrastim products have been marketed; however, a detailed characterization and comparison of variants associated with these products have not been publically reported.

Objective

The objective of this study was to identify and quantify product-related variants in filgrastim reference products and biosimilars thereof that are presently available in highly regulated markets.

Methods

In this study, we used intact and top–down mass spectrometry to identify and quantify product-related variants in filgrastim products. Mass spectrometry has become the method of choice for physicochemical characterization of biopharmaceuticals, allowing accurate and sensitive characterization of product-related variants.

Results

In addition to modifications ubiquitously present in biopharmaceuticals, such as methionine oxidation and asparagine/glutamine deamidation, we identified six different low-level, product-related variants present in some, but not all, of the tested products. Two variants, an acetylated filgrastim variant and a filgrastim variant containing an additional C-terminal tryptophan extension, are newly identified variants.

Conclusion

This study demonstrates that filgrastim products already in widespread clinical use in highly regulated markets differ in low-level, product-related variants present at levels mostly below 1 % relative abundance. This study provides a comprehensive catalog of minor differences between filgrastim products and suggests that the filgrastim product-related variants described here are not clinically relevant when present at low abundance.
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Metadata
Title
Identification of Low-Level Product-Related Variants in Filgrastim Products Presently Available in Highly Regulated Markets
Authors
Anna Hausberger
William C. Lamanna
Martin Hartinger
Andreas Seidl
Hansjoerg Toll
Johann Holzmann
Publication date
01-06-2016
Publisher
Springer International Publishing
Published in
BioDrugs / Issue 3/2016
Print ISSN: 1173-8804
Electronic ISSN: 1179-190X
DOI
https://doi.org/10.1007/s40259-016-0169-2

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