Continuous Countercurrent Tangential Chromatography

连续逆流切向色谱

• 批准号: 8199582
• 负责人: Oleg Shinkazh
• 金额: $ 18.3万
• 依托单位: CHROMATAN CORPORATION
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2012-07-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8199582
• 关键词: Accounting; Beds; Behavior; Binding; Biological; Biological Products; Buffers; Cancer Vaccines; Capital; Cell Culture Techniques; Chromatography; Column Chromatography; Cost Savings; Cytoplasmic Granules; Data; Development; Drops; Drug Costs; Equilibrium; Fiber; Funding; Goals; Grant; Immunoglobulin G; Individual; Investments; Kinetics; Laboratories; Lead; Legal patent; Liquid substance; Marketing; Measurement; Membrane; Methods; Modeling; Monoclonal Antibodies; Myoglobin; Nature; Particle Size; Pharmaceutical Preparations; Phase; Plant Resins; Process; Production; Proteins; Public Health; Pump; Recombinant Proteins; Recombinant Vaccines; Recycling; Research; Resolution; Running; Savings; Series; Small Business Innovation Research Grant; Staging; System; Technology; Testing; Time; United States National Institutes of Health; Universities; Validation; Virus Diseases; Work; absorption; commercial application; cost; countercurrent chromatography; design; design and construction; improved; innovation; manufacturing process; new technology; novel; novel therapeutics; operation; pandemic influenza; particle; pressure; programs; protein purification; prototype; residence; therapeutic protein; therapeutic vaccine

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 biological products, 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 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. 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; a disposable 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 projects a 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.

描述（由申请人提供）：向NIH提交的SBIR第一阶段提案要求为Chromatan，Inc.提供183，000美元的资金。为了证明使用连续逆流切向色谱（CCTC）纯化高价值生物产品的可行性，例如，用于治疗癌症的单克隆抗体或用于保护免受病毒性疾病或流感大流行的重组疫苗。下游加工目前占重组蛋白产品生产总成本的80%。由于填充床色谱柱的有限容量和高成本，细胞培养技术的最新进展已经产生了“下游瓶颈”。通过使用浆液形式的树脂颗粒，CCTC克服了传统柱色谱的许多局限性，该浆液通过由一系列静态混合器和中空纤维膜组件组成的一次性流动路径泵送。渗透物的逆流再循环用于显著提高工艺效率并降低树脂和缓冲液需求，类似于逆流液-液萃取中的行为。将根据临界滤液通量和结合/洗脱动力学的实验测量结果确定最佳膜孔径、树脂粒度和用于CTC的操作条件（例如，错流速率、渗透液流速和静态混合器中的停留时间）。由于不再有任何压降限制，因此可以使用比填充床柱小得多的树脂颗粒，这可以提供显著更快的传质速率。拟议研究的总体目标是设计、构建和测试一个原型CTC系统，该系统能够分离具有大于90%的产物产率和95%纯度的模型蛋白质混合物。Chromatan预计，CCTC技术将为色谱的大规模商业应用带来以下有利影响：与柱色谱相比，树脂体积需求减少5倍;一次性流动路径，无需进行昂贵的清洁验证;可直接扩展至20，000 L的批量;在大规模操作中显著降低资本成本（高达60%）;捕获色谱步骤的总体成本显著节省（高达75%）。这种技术的连续性和一次性性质将通过缩短上市时间和降低生产成本来改善公共卫生，这两者都将导致药物成本的降低。Chromatan预计第五年的市场渗透率为10%，收入为1亿美元。 公共卫生关系：拟议SBIR项目的总体目标是设计、构建和测试能够提供治疗性蛋白质和疫苗的高效、低成本纯化的连续逆流切向色谱系统。与目前的分离技术相比，CCTC的设计具有一次性流动路径，连续操作和较低的资本和运营成本，并将通过降低重要药品的成本和减少将新治疗药物推向市场所需的时间来显著改善公共卫生。