An Integrated Approach for a Structural and Functional Evaluation of Biosimilars: Implications for ErythropoietinReportar como inadecuado

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, Volume 29, Issue 4, pp 285–300

First Online: 03 September 2015


BackgroundAuthorization to market a biosimilar product by the appropriate institutions is expected based on biosimilarity with its originator product. The analogy between the originator and its biosimilars is assessed through safety, purity, and potency analyses.

ObjectiveIn this study, we proposed a useful quality control system for rapid and economic primary screening of potential biosimilar drugs. For this purpose, chemical and functional characterization of the originator rhEPO alfa and two of its biosimilars was discussed.

MethodsQualitative and quantitative analyses of the originator rhEPO alfa and its biosimilars were performed using reversed-phase high-performance liquid chromatography RP-HPLC. The identification of proteins and the separation of isoforms were studied using matrix-assisted laser desorption-ionization time-of-flight mass spectrometry MALDI-TOF–MS and two-dimensional gel electrophoresis 2D-PAGE, respectively. Furthermore, the biological activity of these drugs was measured both in vitro, evaluating the TF-1 cell proliferation rate, and in vivo, using the innovative experimental animal model of the zebrafish embryos.

ResultsChemical analyses showed that the quantitative concentrations of rhEPO alfa were in agreement with the labeled claims by the corresponding manufacturers. The qualitative analyses performed demonstrated that the three drugs were pure and that they had the same amino acid sequence. Chemical differences were found only at the level of isoforms containing N-glycosylation; however, functional in vitro and in vivo studies did not show any significant differences from a biosimilar point of view.

ConclusionThese rapid and economic structural and functional analyses were effective in the evaluation of the biosimilarity between the originator rhEPO alfa and the biosimilars analyzed.

Electronic supplementary materialThe online version of this article doi:10.1007-s40259-015-0136-3 contains supplementary material, which is available to authorized users.

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Autor: Alessandra Gianoncelli - Sara A. Bonini - Michela Bertuzzi - Michela Guarienti - Sara Vezzoli - Rajesh Kumar - Andrea Delb


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