A Cost-effective Purification Process for Erythropoietin Biosimilar through Downstream Process Engineering

Well-characterized and scalable downstream process for purification of biologics is extremely demanding for delivering quality therapeutics to patients at a reasonable price. Erythropoietin (EPO) is a blockbuster biologic with diverse clinical applications but its application is limited to financially well-off societies due to high price. The high price of EPO is associated with the technical difficulties related to the purification challenge to obtain qualified product with a cost-effective defined process. Though there are reports for purification of EPO but there is no report of well-characterized downstream process with critical process parameters (CPPs) that can deliver EPO consistently satisfying the quality target product profile (QTPP), which is a critical regulatory requirement. To advance the field, we applied quality by design (QbD) principle and design of experiment (DoE) protocol to establish an effective process, which is scalable up to 100x batch size satisfying QTPP. We have successfully transformed the process from static mode to dynamic mode and validated. Insignificant variation (p> 0.05) within and between 1x, 10x and 100x batches showed that the process is reproducible and seamlessly scalable. The biochemical analysis along with the biofunctionality data ensures that the products from different-scale batches were indifferent and comparable to a reference product. Our study thereby established a robust and scalable downstream process of EPO biosimilar satisfying QTPP. The technological scheme presented here can speed-up the production of not only EPO but many other life-saving biologics and make them available to mass population at a reduced cost.