This study shows comparability analysis between a biosimilar product and an innovator mAb in both Host Cell Protein (HCP) and higher order structure level. Both studies were carried out using a micro flow ACQUITY UPLC system interfaced to a high resolution mass spectrometry (Synapt HDMS). The HCP study concludes that two HCPs (epidermal growth‐factor like protein 8 and WD repeat containing protein 37) were found in both the innovator and the biosimilar mAbs, however, the biosimilar mAb has higher level of HCP compare to the innovator (2‐4 fold higher). Protein tertiary structure analysis was conducted using Hydrogen Deuterium Exchange Mass Spectrometry (HDX MS), results showed the conformation for both mAbs are highly comparable except a minute difference in CH2 domain. Our study shows great promise in adapting these analytical capabilities into biosimilar drug development process.