Abstract
The approval and granting of marketing authorization for a putative biosimilar is based on strong comparability studies with its biological reference product. This is due to the complexity of the structure and nature of the manufacturing process of biological drugs. Hence, a rigorous analytical workflow for chemical characterization and clinical trials to evaluate the efficacy and safety is required to demonstrate their high similarities to the reference drug. This work is focused on the comparison of the originator of filgrastim with three of its biosimilars by evaluating their structural similarity and biological activity. Qualiquantitative analyses were performed by MALDI-TOF/TOF-MS and RP-HPLC-UV. An innovative functional assay using zebrafish as the animal model was developed to evaluate the biological activities of the drugs. The different analyses performed in this study highlighted the structural similarity of biosimilar drugs and their originator. This result was further confirmed by a similarin vivobiological activity.
Highlights
Biosimilar drugs have been on the market for some decades
We show the results of a comparative study among the biotechnology drug GRA and three of its biosimilars NIV, TEV, and ZAR. is is the rst time, to the best of our know how, in which all four drugs distributed in Italy are compared at the same time and in the same way both from a structural and functional point of view
Quantitative and qualitative chemical evaluation has been assessed by recognized techniques such as RP-HPLC-UV and MALDITOF-MS while biological activity has been studied in vivo using an innovative experimental animal model represented by zebra sh embryos
Summary
Biosimilar drugs have been on the market for some decades now. the use of biosimilars in Italy and entire European Union remains to be controversial. The complexity of the protein structure and the manufacturing process selected (i.e., host cell, production system, and purification) could lead to minor differences in the physiochemical properties of the biological drugs. E sequence of filgrastim is identical to isoform B of G-CSF isolated from human cells, except for two modifications: (1) the presence of a methionine in the N terminal position of the recombinant protein instead of an alanine (r-met Hu G-CSF) and (2) the absence of glycosylation [9, 12], which is due to the lack of posttranslational modifications mechanism in the E. coli expression system Despite these differences, filgrastim preserves the biological activity of the isoform B of human G-CSF [13]. E results obtained indicate similar functional and structural properties of all tested compounds supporting the assessment of biosimilarity among them
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