Comparative Analytical Characterization of Selected Biosimilar Formulations Available in India

Abstract

The significance of performing a comparative analytical similarity assessment cannot be newlineoverstated in the process of evaluating the quality of a biosimilar product and its regulatory newlinesubmission. This is due to the fact that biosimilar products are not identical to the innovator newlineproduct. Moreover, it is considered essential to establish appropriate shelf-life and storage newlineconditions for a drug product to ensure the safety and efficacy of the product over its intended newlineshelf-life, following its market authorization. newlineIn this thesis, analysis of critical product attributes of marketed Bevacizumab biosimilar-1, newlineand biosimilar-2 (Bio-1, and Bio-2) and Erythropoietin-1, Erythropoietin-2, and newlineErythropoietin-3 (Epo-1, Epo-2, and Epo-3) biosimilar products were carried out in newlinecomparison to their reference product using state-of-the-art analytical techniques. Quantitative newlineestimation of native protein was performed using UV-Visible spectrophotometer at 280 nm newline(UV280) and reverse phase high performance liquid chromatography (RP-HPLC) method, high newlineorder structure characterization was done using attenuated total reflectance-fourier transform newlineinfrared spectrophotometer (ATR-FTIR) and Far-UV circular dichroism (Far-UV CD) method, newlinecharge and size variant analysis was carried out using imaged capillary isoelectric focusing newline(iCIEF) and capillary electrophoresis coupled with sodium dodecyl sulfate (CE-SDS) technique newlinein both reduced and non-reduced condition. Matrix assisted laser desorption ionization newlinecoupled with time of flight detector (MALDI-TOF) and liquid chromatography coupled with newlineelectrospray ionization and quadrupole time of flight detector (LC-ESI-QTOF) techniques newlinewere used to carry out intact mass analysis for Bevacizumab products. newlineFurthermore, the stability of Bevacizumab marketed formulations after exposure to thermal, newlinechemical, and mechanical stress conditions is also discussed in this thesis. The profile of newlineaggregates, other product-related impurities, and any alterations to high order structure newlinetriggered as a function of thermal,