Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 222.38K | Year: 2016
DESCRIPTION provided by applicant The overall goal of the proposed 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 reduction in production costs for life saving therapies that treat conditions such as cancer Crohnandapos 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 AAPS meeting andquot It is predicted that manufacturing will change in the next years as current manufacturing practices are abandoned in favor of cleaner flexible more efficient continuous manufacturing andquot 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 The CCTC technology was developed by the Chromatan Corporation and supported by NIH with over $ M in funding Phase I grant R RR A Phase II grant R GM CCTC has shown over X improvement in productivity vs conventional columns with equivalent product quality in multiple pilot studies CCTC is being commercialized by Chromatan in partnership with Thermo Fisher Scientific Overall commercialization of the ICS system will have the following impacts on bio production Continuous operation will lead to lower capital cost and lower equipment footprint Single use and closed system features will reduce capital cost enable flexible manufacturing and eliminate cleaning and cleaning validation requirements True steady state operation will enable in line process monitoring of bioreactor and purification performance leading to better robustness and product quality ICS flexibility will enable manufacturers to launch processes faster and at a lower cost resulting in better availability of life saving therapis to patients around the world PUBLIC HEALTH RELEVANCE The overall goal of the proposed 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 reduction in production costs for life saving therapies that treat conditions such as cancer Crohnandapos s disease and Rheumatoid Arthritis
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 183.00K | Year: 2011
DESCRIPTION (provided by applicant): SBIR Phase I proposal to NIH requests 183,000 funding for Chromatan, Inc. to demonstrate the feasibility of using Continuous Countercurrent Tangential Chromatography (CCTC) for the purification of high value biologicalproducts, e.g., monoclonal antibodies for the treatment of cancer or recombinant vaccines for protection against viral disease or a flu pandemic. Downstream processing currently accounts for as much as 80% of the overall cost of production of recombinantprotein 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. Countercurrent recycling of the permeate is used to significantly increase process efficiency and reduce resin and buffer requirements, analogous to the behavior in countercurrent liquid-liquid extraction. The optimal membrane pore size, resin particle size, and operating conditions for CCTC (e.g. crossflow rate, permeate flow rate, and residence time in the static mixers) will be determined from experimental measurements of the critical filtrate flux and the binding / elution kinetics. CCTC can employ much smaller resin particles than packed bed columns, since there is no longer any pressure drop limitation, which can provide significantly faster mass transfer rates. The overall goal of the proposed research is to design, construct, and test a prototype CCTC system capable of separating a model protein mixture with greater than 90% product yield and 95% purity. Chromatan envisions that CCTC technology will provide the following favorable impacts for large-scale commercial applications of chromatography: 5-fold reduction in resin volume requirements compared with column chromatography; adisposable flow path that eliminates the need for costly cleaning validation; straightforward scalability up to batch volumes of 20,000 L; significant reduction of capital costs (up to 60%) in large-scale operations; significant overall cost savings (up to 75%) for capture chromatography steps. 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 projectsa fifth year market peneratraion of 10% and revenues of 100 million. PUBLIC HEALTH RELEVANCE: The overall goal of the proposed SBIR project is to design, construct, and test a Continuous Countercurrent Tangential Chromatography system 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.
Dutta A.K.,Chromatan Corporation |
Dutta A.K.,Pennsylvania State University |
Tran T.,Chromatan Corporation |
Napadensky B.,Chromatan Corporation |
And 7 more authors.
Journal of Biotechnology | Year: 2015
Recent studies using simple model systems have demonstrated that continuous countercurrent tangential chromatography (CCTC) has the potential to overcome many of the limitations of conventional Protein A chromatography using packed columns. The objective of this work was to optimize and implement a CCTC system for monoclonal antibody purification from clarified Chinese Hamster Ovary (CHO) cell culture fluid using a commercial Protein A resin. Several improvements were introduced to the previous CCTC system including the use of retentate pumps to maintain stable resin concentrations in the flowing slurry, the elimination of a slurry holding tank to improve productivity, and the introduction of an "after binder" to the binding step to increase antibody recovery. A kinetic binding model was developed to estimate the required residence times in the multi-stage binding step to optimize yield and productivity. Data were obtained by purifying two commercial antibodies from two different manufactures, one with low titer (~0.67. g/L) and one with high titer (~6.9. g/L), demonstrating the versatility of the CCTC system. Host cell protein removal, antibody yields and purities were similar to those obtained with conventional column chromatography; however, the CCTC system showed much higher productivity. These results clearly demonstrate the capabilities of continuous countercurrent tangential chromatography for the commercial purification of monoclonal antibody products. © 2015 Elsevier B.V.