Continuation Application for the development of Integrated continuous and single-use (ICS) bioproduction platform (Phase IIB)

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PROJECT SUMMARY / ABSTRACT The overall goal of the proposed Phase IIB SBIR project is to commercialize an Integrated Continuous and Single-use bio-production platform (ICS) for flexible and robust manufacturing of therapeutic proteins. This novel platform will enable continuous, single-use, and low cost purification of therapeutic proteins. Successful commercialization of the ICS system will lead to at least a 50% reduction in production costs for life saving therapies that treat conditions such as cancer, Crohn’s disease, and Rheumatoid Arthritis. Continuous and flexible single-use processing for monoclonal antibodies and other bio- therapeutics has been established as a significant unmet need. Dr. Janet Woodcock, Director of the FDA Center for Drug Evaluation and Research, stated in a 2011 AAPS meeting: “It is predicted that manufacturing will change in the next 25 years as current manufacturing practices are abandoned in favor of cleaner, flexible, more efficient continuous manufacturing.” Significant bottlenecks in downstream processing as well as the explosive growth in the number of therapeutics in development are the primary drivers of this unmet need. The purpose of the ICS system will be to integrate two of the most promising flexible and continuous technologies in the market – single-use perfusion and the novel single-use purification system called Continuous Countercurrent Tangential Chromatography (CCTC). CCTC has shown over 10X improvement in productivity vs. conventional columns with equivalent product quality in multiple pilot studies. Through our Phase II efforts the CCTC pilot system is now launched to the market with the first sale booked in 2021. We were also able to develop a 2nd generation flow path that will utilize 3D printed Dean Vortex Separators as well as specially developed large pore size membranes enabling long-term and fouling free operation of the ICS system. The Phase IIB effort will focus on finalizing the pilot scale integration of the ICS framework and scale up of the platform to cGMP. The program will be supported by multiple strategic partners – Proconex for automation, Purolite for resin manufacturing, and NewAge Industries for single-use and 3D printing. The project will also be supported by large biopharma players that have already invested into our technology – Merck, Roche and Takeda. Overall, commercialization of the ICS system will have the following impacts on bio-production: 1. Continuous operation will lead to lower capital cost and lower equipment footprint. 2. Single-use and closed system features will reduce capital cost, enable flexible manufacturing, and eliminate cleaning and cleaning validation requirements. 3. True steady state operation will enable in-line process monitoring of bioreactor and purification performance, leading to better robustness and product quality. 4. ICS flexibility will enable manufacturers to launch processes faster and at a lower cost resulting in better availability of life saving therapies to patients around the world. The ICS system will be a key component of the next generation vision we call NextGnBio – a quick-to-launch POD-like facility based on a joint vision with GCON. NextGnBio will save over 80% in capital, 50% in operating costs and enable a 50% acceleration of rapid scale up of life saving medicines.