• Global interest in biosimilars as affordable substitutes has increased due to the rising costs of biologic therapies. Developing reliable, scalable, and financially viable downstream purification techniques is essential to the production of biosimilars. Within the context of a standardized platform process for biosimilars, this study examines the lifecycle cost analysis and performance evaluation of Protein A chromatography resins, a crucial step in the purification of monoclonal antibodies (mAbs). The work combines downstream screening of three commercially available Protein A resins—MabSelect SuRe (GE Healthcare), Amsphere A3 (JNC Corporation), and Praesto Jetted A50 (Purolite)—with enhanced upstream fed-batch bioprocessing utilizing CHO cells. Key metrics such dynamic binding capacity (DBC), recovery yield, elution volume, pressure drop, impurity clearing (HCP, DNA), protein A leakage, and cleaning stability were examined for each resin utilizing a unified chromatographic methodology to guarantee consistency. Amsphere A3 outperformed the other resins in the test, showing the lowest operating pressure, the highest DBC (65 mg/mL), and the most effective impurity and DNA clearance with the least amount of protein A leaching (0.8 ng/mg). Despite having the lowest elution volume and the best recovery yield, Praesto Jetted A50 displayed a slight drop in DBC across several cleaning cycles, indicating moderate reusability. The viability of a platform strategy for biosimilar production, which offers scalability, regulatory compliance, and shortened development schedules, was confirmed by the integration of upstream and downstream data. All things considered, this study emphasizes how important resin selection is in determining the quality and cost-effectiveness of producing biosimilars. By maximizing lifespan cost and performance at the industrial scale, it offers a useful, data-driven framework for resin selection and process standardization, facilitating wider access to biosimilars.

Biosimilar, Monoclonal antibodies (mAbs), Protein A chromatography, Downstream purification, CHO cells, Dynamic binding capacity (DBC), Resin performance, Impurity clearance, Protein A leaching, Lifecycle cost analysis, Platform process, Bioprocess optimization, Recovery yield, Cleaning cycle stability, Scalable manufacturing, Regulatory compliance, Process standardization