Physicochemical and Functional Characterization of Medicinal Product Rinsulin® R

Introduction. Currently, biosimilars have found quite widespread use in the treatment of a number of chronic and life-threatening diseases. Thanks to them, there is a significant decrease of the economic pressure of biological drugs on the health care system and wide access of patients to effective and safe medicines is ensured. One of the most important stages of proving biosimilarity is the physicochemical and functional characterization of proteins. This set of studies is generally accepted, as sensitive as possible and allows us to give a conclusion about the compliance of the biosimilar with the original drug. Aim. Conducting physicochemical and functional characterization of medicinal product Rinsulin® R (GP40051) in comparison with the original drug Humulin® Regular. Materials and methods. Primary structure was analyzed by high-performance liquid chromatography with mass spectrometry detection and matrix assisted laser desorption/ionization. The identity of the higher protein structures was proved by the methods of circular dichroism, capillary isoelectric focusing, spectrometry and dynamic light scattering. The comparability of the impurity profiles of the preparations was evaluated using the methods of exclusive chromatography and reverse-phase high-performance liquid chromatography. Functional characterization included a metabolic cell test "glucose uptake" and insulin receptor–binding assay (kinetics of binding to type A and B receptors, phosphorylation of insulin receptor). Results and discussion. In the course of this research, the identity of the physicochemical and functional characteristics of GP40051 was shown. A complete overlap of primary sequence, high-order structures and impurity profiles was demonstrated between the comparison drug GP40051 and the reference drug Humulin® Regular. Functional studies have shown that GP40051 and Humulin® Regulars have the same activity. Conclusion. The results of the quality comparability study demonstrated similarity of Rinsulin® R to the reference medicinal product Humulin® Regular, providing the scientific basis for conducting a specifically designed clinical programme, and supported registration in Russian Federation.