Assessment of structural and functional similarity of biosimilar products: Rituximab as a case study

Abstract

Biosimilars are products that are similar in terms of quality, safety, and efficacy to an already licensed reference/ innovator product and are expected to offer improved affordability. The most significant source of reduction in the cost of development of a biosimilar is the reduced clinical examination that it is expected to undergo as compared to the innovator product. However, this clinical relief is predicated on the assumption that there is analytical similarity between the biosimilar and the innovator product. As a result, establishing analytical similarity is arguably the most important step towards successful development of a biosimilar. Here, we present results from an analytical similarity exercise that was performed with five biosimilars of rituximab (Ristova®, Roche), a chimeric mouse/ human monoclonal antibody biotherapeutic, that are available on the Indian market. The results show that, while the biosimilars exhibited similarity with respect to protein structure and function, there were significant differences with respect to size heterogeneity, charge heterogeneity and glycosylation pattern.

ATR-FTIR spectroscopy and spectroscopic imaging for the analysis of biopharmaceuticals

“…In contrast, FTIR spectroscopy, particularly ATR-FTIR spectroscopy, caters to these requirements. For example, ATR-FTIR spectroscopy was used to assure that the secondary structure of the biosimilar Ristova® was similar to that of the original biologic [86]. In addition, using FTIR spectroscopy, quality control to a high standard has been carried out on Humalog®, an approved biosimilar, to investigate stability at varying temperatures [67].…”

Understanding the mechanism of copurification of “difficult to remove” host cell proteins in rituximab biosimilar products

“…Structural analysis included examination of the secondary and tertiary structure using far‐UV CD and fluorescence spectroscopy of the mAb biosimilars. Far‐UV CD spectra were recorded in the range of 200–250 nm at 25°C on a JASCO J‐815 spectropolarimeter according to Reference .…”

Rituximab biosimilars for lymphoma in Europe

“…Reditux TM (Dr. Reddy's Laboratories) was approved for use in India in 2007 and is also distributed in markets in Asia and Latin America. Available analytical data for Reditux TM include structural and functional comparisons with reference rituximab (MabThera®/Rituxan®/Ristova® [alternative brand name used by Roche in India]) [103][104][105]. These data show similarities between the biomimic and reference medicine in terms of size heterogeneity, higher-order structure, and intact and reduced mass.…”