Strategies for continuous biologics purification with new affinity membranes

Clemson University, Clemson SC

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Abstract

Project Summary Innovations in continuous bioprocessing like those that are proposed will have a significant impact on the industry and human health by dramatically improving efficiency and flexibility in existing facilities and lowering the cost of biologic drugs. The biopharmaceutical industry is expanding rapidly and globally. The rapid pace of new product development is presenting significant problems for biopharmaceutical manufacturers, who are faced with the dilemma of how best to meet the shifting demands of scale and product diversity while minimizing financial risk in building and validating new facilities. There is consensus that continuous bioprocessing using disposable technologies can address this problem, but this paradigm change will require innovations in purification materials and processes. It also will require collective action from academia and industry via knowledge sharing, like the proposed effort, to develop and model conceptual designs for an end- to-end continuous process. The goal of this research project is to synthesize new purification materials and create new computational algorithms and innovative design strategies for the continuous purification of biologics. We will use these innovations to test the hypothesis that affinity membranes with high dynamic binding capacity and short cycle time can be used for the capture step of a continuous antibody purification process to increase productivity and lower cost relative to the current platform purification process. Existing materials for capture step chromatography are limited to resin beads that require long residence times (order of minutes) to attain high binding capacity. We propose to use a unique new polymerization strategy to synthesize affinity membranes with high capacity at short residence times (order of seconds). On the computational modeling side, we will create customized computational algorithms that will enable efficient comparison of innovative process design alternatives for a continuous downstream purification process. The new algorithms will be open access for use in commercial software packages. We will use the new modeling algorithms and performance data for the new membranes to evaluate, for the first time, continuous antibody purification processes that employ an affinity membrane chromatography capture step. Techno-economic modeling will quantify gains in production capacity and cost reduction for various continuous purification process configurations. A key feature of the research project is an internship program to provide PhD students experience and training in industrial scientific research under the guidance and mentorship of biopharmaceutical industry scientists. Providing meaningful internships to PhD students will enable the students to gain firsthand knowledge of the culture, environment, and intellectual challenges present in the industry.