Application Notes

Rapid and precise biosimilar candidate profiling by nanoDSF

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Biosimilar Profiling Application Note NT-PR-010 Rapid and Precise Biosimilar Candidate Profiling by nanoDSF Dennis Breitsprecher 1 , Florian Beck 2 and Lukasz Kacprzyk 2 1 NanoTemper Technologies GmbH, Munich, Germany 2 UGA Biopharma GmbH, Hennigsdorf, Germany Abstract The development of biosimilars requires extensive physicochemical characterization of biosimilar candidate molecules which should match the quality profile of the reference molecule (originator). Here we use a novel method of thermal unfolding profiling to rapidly screen a variety of Fc-fusion protein biosimilar candidates. The best-in-class precision of the NanoTemper Technologies Prometheus NT.48 nanoDSF instrument allowed for the ranking of biosimilar candidates according to the comparability of their unfolding profiles to the reference molecule. The results were in excellent agreement with conventional screening methods, while dramatically reducing sample consumption and measurement times. Thus, nanoDSF (miniaturized differential scanning fluorimetry) is a new and powerful tool for rapid screening approaches in biosimilar development. It enables narrowing down the number of promising candidates in hours instead of days or weeks. Introduction In contrast to the development of new biological entities (NBEs), where much time and resources are invested in clinical trials, the focus in the development of biosimilar medicinal products lies on a comprehensive physicochemical and biological protein characterization to ensure that the molecular fingerprint of the biosimilar matches that of the originator as closely as possible (van Aerts et al, 2014). Commonly, various analytical methods such as high-performance liquid chromatography, capillary electrophoresis, mass spectrometry, Raman spectroscopy, isoelectric focusing, and CD-spectroscopy are used to evaluate the degree of similarity between molecules (Berkowitz et al, 2012; Bui et al, 2015; Cai et al, 2011). While useful for in-depth characterization of biosimilar candidates, these methods suffer from either low throughput, high sample consumption, or laborious data analysis, and thus are not very well suited for rapid screening of a large number of biosimilar candidates. The 3D-structure of biosimilars is typically very complex since it is determined by the sum of a plethora of low-affinity intramolecular interactions.

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