A new, integrated, continuous purification process template for monoclonal antibodies: Process modeling and cost of goods studies.

An evolving biopharmaceutical industry requires advancements in biomanufacturing that offer increased productivity and improved economics without sacrificing process robustness. Accordingly, we have developed a new monoclonal antibody purification template comprised of flocculation-based clarification, capture by continuous multi-column protein A chromatography and flow-through polishing. The new process offers a robust, single-use manufacturing solution while significantly reducing overall cost of goods. Modeling studies verify that the individual clarification, capture and polishing solutions offer significant advantages as stand-alone unit operations. These technologies were also designed to be integrated into a continuous purification template. Process modeling studies have been used to highlight both cost and operational advantages of the new process template. Depending on scale, savings of more than 20% and 60% were seen for commercial and clinical operation, respectively. Integrating the technologies into a continuous process consistently offered additional cost advantages. During template development, process modeling was instrumental in highlighting the importance of identifying technologies that provided high product yield and purification factors. Additionally, high product concentration and eliminating the need for intermediate product dilution emerged as important considerations for newly developed unit operations. Combining experimental work with insights from modeling can significantly improve the outcome of product and process development.