Investigation of light induced degradation of Aryotrust® (a biosimilar of trastuzumab) by ion exchange chromatography and size exclusion chromatography

Abstract

Introduction: Trastuzumab is a humanized monoclonal antibody, which is specifically targeting the extracellular domain of the human epidermal growth factor receptor 2 (HER2), and it is indicated for the treatment of HER2 positive early or metastatic breast cancer and metastatic gastric cancer.Scope: This study was designed to evaluate the physicochemical stability of the biological product, AryoTrust® (biosimilar of trastuzumab, manufactured by ArioGen Pharmed compony) that exposed to the light stress.Methods: To determine the effect of light stress on the physicochemical properties of AryoTrust®, the drug was exposed to more than 1.2×106 Luxh visible light and 200Wh/m2 Ultaviolet radiation (according to ICH Q1B Guidline). For analysis a combination of physicochemical methods as size exclusion chromatography (SEC) and cation exchange chromatography (CEX) was used. SEC and CEX methods were developed and validated according to International Conference Harmonization (ICH) guidelines.Results: Validation results of the both Cation Exchange Chromatography and Size Exclusion Chromatography methods showed the linearity of applied methods (R2>0.99), but the accuracy, precision and robustness of the developed methods, need more studies and analyses. The results obtained from the mentioned methods, showed that the light stress applied to the AryoTrust®, had measurable effect on the physicochemical stability of this monoclonal antibody.Conclusion: The light stress applied to AryoTrust® affected the molecular size but didn't affect ion profile of the drug. Also, in order to have the validated methods from the robustness and accuracy view, further study and analysis are recommended to confirm the obtained results according to the ICH guidelines.