Assessment of Structural and Functional Comparability of Biosimilar Products: Trastuzumab as a Case Study
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ORIGINAL RESEARCH ARTICLE
Assessment of Structural and Functional Comparability of Biosimilar Products: Trastuzumab as a Case Study Srishti Joshi1 · Anurag S. Rathore1
© Springer Nature Switzerland AG 2020
Abstract Background Biotherapeutics are protein products generated using recombinant DNA technology and manufactured in prokaryotic or eukaryotic cells. It is often said that “the process is the product” and thereby the effect of the manufacturing process is etched on the final product in the form of its heterogeneity. For any biotherapeutic, the acceptable range of the critical quality attributes is defined based on the expected impact of a specific variation on the product stability, safety, and efficacy. For a biosimilar to receive regulatory approval, the manufacturer must demonstrate analytical and clinical comparability with the originator product. As this is mandatory, every biosimilar manufacturer performs this exercise for each biosimilar product under development. However, few reports of thorough evaluation of the quality of biosimilar products are available in the literature. Objective We examined the structural and functional comparability of biosimilars of trastuzumab, a humanized monoclonal antibody biotherapeutic. The originator product, Herclon (Roche), was compared with four marketed biosimilars: Trasturel from Reliance Life Sciences, Canmab from Biocon, Vivitra from Zydus Ingenia, Hertraz from Mylan. Methods Structural comparability was established using mass spectrometry and spectroscopic techniques such as Fourier transform infrared spectroscopy, differential light scattering, circular dichroism, and fluorescence spectroscopy. Stability was compared by performing accelerated thermal stress studies. Functional comparability was established via surface plasmon resonance and biological assays such as antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Results With respect to comparability, one biosimilar exhibited significant differences in multiple attributes, such as lower percentage of monomer content and main charge variant species, lower percentage of aglycosylated glycoform G0, and lower estimated potency values. Conclusions Overall, the results indicated general similarity with respect to structure and function, but we found variations with respect to size heterogeneity, charge heterogeneity, and glycosylation pattern in each of the biosimilars. Key Points A structural and functional comparability assessment was carried out for trastuzumab biosimilars and the originator product. The products were comparable with respect to structure and function, but variations existed with respect to size heterogeneity, charge heterogeneity, and glycosylation pattern in each of the biosimilars. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s40259-020-00404-3) contains supplementary material, which is available to authorized users. * Anurag S. Rathore [email protected] 1
Department of Chemical Engineering,
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