This SBIR Phase II proposal to NIH requests $985,000 funding for Chromatan, Inc. to scale up and commercialize Continuous Countercurrent Tangential Chromatography (CCTC) for the purification of high value biological products, e.g., monoclonal antibodies for the treatment of cancer and arthritis. Downstream processing currently accounts for as much as 80% of the overall cost of production of recombinant protein products. Recent advances in cell culture technology have created a "downstream bottleneck" due to the limited capacity and high expense of packed bed chromatography columns. CCTC overcomes many of the limitations of conventional column chromatography by using resin particles in the form of a slurry, which is pumped through a disposable flow path consisting of a series of static mixers and hollow fiber membrane modules. The CCTC system eliminates column packing, which is time-consuming and labor intensive. The system components are much less expensive and linearly scalable enabling a fully disposable flow path design for large scale systems. This is particularly attractive for production of clinical product batches or for use in multi-product facilities, e.g.,in combination with single-use bioreactors. The overall goal of the proposed research is to design, construct and validate the first cGMP CCTC system. In Year 1, the technology will be refined by testing the performance of the CCTC alpha system at process development laboratories of our early adopters - Fujifilm Diosynth and Regeneron. In Year 2, Chromatan will scale up the technology to be able to process at least 1 kg of monoclonal antibody in the clinical cGMP environment. Chromatan envisions that CCTC technology will provide the following favorable impacts for large-scale commercial applications of chromatography: ? 10-fold reduction in resin volume requirements compared with column chromatography ? A disposable flow path, eliminating costly cleaning, cleaning validation, and column packing ? Straightforward scalability and the ability to purify up to 1 kg of MAB ? Significant reduction of capital investment (80%) in large-scale operations, "pay as you make" approach with razor / razor blade design. Reduction of capital risk. ? Significant overall savings (65%) on downstream processing costs for clinical capture chromatography. The continuous and disposable nature of this technology will improve public health by decreasing time to market and reducing production costs, both of which will lead to a reduction in drug costs. Chromatan projects a fifth year market penetration of 10% and revenues of $50 million.
The overall goal of the proposed SBIR project is to scale up and commercialize Continuous Countercurrent Tangential Chromatography (CCTC) technology capable of providing highly efficient and low cost purification of therapeutic proteins and vaccines. CCTC is designed to have a disposable flow path, continuous operation, and lower capital and operating costs compared to current separation technologies, and will lead to significant improvements in public health by reducing the cost of important drug products, and by decreasing the time required to bring new therapeutic drugs to market.