Estimation of Process Related Impurities in Biosimilar

Abstract

A biosimilar is a biologic medicine which is highly similar to the existing approved reference drugs. Due to cost effectiveness in comparison to the existing original drugs, biosimilars are expected to cover the huge market in coming years. However, complexity of biologicals developing and manufacturing high quality biosimilars require in depth knowledge and expertise. Host Cell Protein (HCPs) constitutes major portion of bioprocessing attached impurities. Regulatory agencies like WHO, European Medicines Agency (EMA) expects negligible amount of HCPs in final drug due to its possible immunogenic effects in human. Hence, to match the safety policy requirements it is necessary to remove HCPs from final substance. There are several methodological steps to remove impurities associated with biosimilar production includes chromatography and filtration, however some residual amount of HCP remains in the product. To quantify this residual impurity, a more sensitive and high throughput method sandwich ELISA has been used in this study. Additionally enterokinase is used to cleave the generated fusion product (final drug is a peptide), an ELISA based method to demonstrate clearance of this enzyme has been developed and tested on in-process samples and final drug substance. The overall aim of this dissertation is to work on assays that impact the impurity profile of the drug substance, this is critical to demonstrate safety of the drug.