Physicochemical and Biological Characterization of RTXM83, a New Rituximab Biosimilar

Analytical Similarity Assessment of Biosimilars: Global Regulatory Landscape, Recent Studies and Major Advancements in Orthogonal Platforms

“…Over the years, differential scanning calorimetry (DSC) has gained popularity as a fast and sensitive tool to measure thermodynamic stability and thermal unfolding pattern, where conformational changes are reflected as changes in characteristic transition/melting temperatures ( T m) of one or multiple protein domains ( Visser et al, 2013 ; Magnenat et al, 2017 ; Lee et al, 2019 ) ( Supplementary Table S4 ). In recent times, time-correlated single-photon counting (TCSPC) is being used as an orthogonal technique to DSC to measure fluorescence lifetime distributions by the time-resolved intensity decay of protein ( López-Morales et al, 2015 ; Mendoza-Macedo et al, 2016 ; Cerutti et al, 2019 ) ( Supplementary Table S4 ). Other orthogonal tools include a fast, robust, low volume technique, i.e., nano differential scanning fluorimetry (nanoDSF) based on changes in intrinsic fluorescence upon thermal denaturation in a label-free fashion ( Joshi et al, 2020 ; Wen et al, 2020 ) and IM-MS with collision-induced unfolding (CIU) ( Kang et al, 2020b ; 2020c ) with limited applications so far ( Supplementary Table S4 ).…”

Rituximab biosimilar RTXM83 versus reference rituximab in combination with CHOP as first-line treatment for diffuse large B-cell lymphoma: a randomized, double-blind study

“…RTXM83 is a proposed biosimilar developed by mAbxience Research S. L. (Madrid, Spain) to the reference product rituximab (MabThera V R /Rituxan V R ), that showed similarity in psychochemical, structural properties, and biological functions in in vitro studies [10,11], further complemented by an in vivo PK and PD study in cynomolgus monkeys, where RTXM83 was found to be comparable to reference rituximab (R-rituximab) in terms of PK and PD response (CD20þ cell depletion) and toxicological profile (data on file).…”

Comparative biosimilar quality studies between a rituximab product and MabThera

“…Comparing the resultant peaks belonging to these peptides can serve as a powerful tool to compare biosimilars to their originators or to compare different lots of the same product. Results from this test showed that both Zytux and MabThera exhibited similar peptide mapping profiles (Figure 3) which indicate that both products share the same primary structure to a large extent [30]. It is also worth mentioning that peptide mapping should be better done on the deglycosylated protein samples to excludes any differences in the protein primary structure which can come from the different retention times and intensities of glycopeptides, which are usually heterogeneous.…”