Phase II Commercialization of Continuous Countercurrent Tangential Chromatography

连续逆流切向色谱的第二阶段商业化

• 批准号: 8735973
• 负责人: Oleg Shinkazh
• 金额: $ 40.71万
• 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 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8735973
• 关键词: Accounting; Antibodies; Arthritis; Beds; Biological Products; Bioreactors; Capital; Cell Culture Techniques; Cells; Chromatography; Clinical; Column Chromatography; Cyclic GMP; Data; Development; Devices; Documentation; Drops; Drug Costs; Environment; Fiber; Funding; Goals; Grant; Harvest; Hour; Housing; Investments; Laboratories; Lead; Legal patent; Liquid substance; Location; Marketing; Membrane; Monoclonal Antibodies; Nature; Penetration; Performance; Pharmaceutical Preparations; Phase; Plant Resins; Process; Production; Productivity; Proteins; Public Health; Pump; Qualifying; Recombinant Proteins; Research; Risk; Savings; Series; Site; Small Business Innovation Research Grant; Software Validation; System; Technology; Testing; Therapeutic Monoclonal Antibodies; Time; Ultrafiltration; United States National Institutes of Health; Validation; absorption; cancer therapy; commercial application; commercialization; cost; countercurrent chromatography; design; design and construction; improved; innovation; novel therapeutics; operation; particle; performance tests; phase 1 study; pressure; programs; prototype; public health relevance; scale up; success; therapeutic protein; therapeutic vaccine; validation studies

DESCRIPTION: 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.

描述：这项SBIR II期建议NIH要求Chromatan，Inc。要求$ 985,000的资金，以扩大和商业化连续的逆流切线色谱法（CCTC），以纯化高价值生物学产品，例如单克隆抗体，用于治疗癌症和关节炎。目前，下游加工占重组蛋白质产品总生产成本的80％。细胞培养技术的最新进展由于容量有限和填充床色谱柱的高昂费用而创造了“下游瓶颈”。 CCTC通过使用泥浆的形式使用树脂颗粒克服了常规柱色谱的许多局限性，该浆料通过一次性流动路径泵送，该流动路径由一系列静态混合器和空心纤维膜模块组成。 CCTC系统消除了列的柱子包装，这是耗时且劳动密集型的。该系统组件的价格要便宜得多，可扩展性可扩展，从而为大规模系统提供了完全一次性的流路设计。这对于生产临床产品批次或用于多产品设施的生产特别有吸引力，例如与一次性生物反应器结合使用。拟议研究的总体目标是设计，构建和验证第一个CGMP CCTC系统。在第一年，该技术将通过测试CCTC Alpha系统在我们的早期采用者的过程开发实验室-Fujifilm Diosynth和Regeneron的过程中进行完善。在第二年，Chromatan将扩展该技术，以便能够在临床CGMP环境中处理至少1公斤的单克隆抗体。 Chromatan设想CCTC技术将对色谱法的大规模商业应用产生以下有利的影响：？与色谱柱色谱法相比，树脂体积需求减少了10倍？一次性流动路径，消除了昂贵的清洁，清洁验证和圆柱包装？直接的可伸缩性和净化多达1 kg mAb的能力？大规模运营中资本投资的大幅降低（80％），“按照剃须刀 /剃刀刀片设计”的“付费”方法。降低资本风险。 ？临床捕获色谱法下游加工成本的总体节省（65％）。该技术的持续和倾向性质将通过减少上市时间和降低生产成本来改善公共卫生，这两者都会导致毒品成本降低。染色体投射五年级的市场 渗透率为10％，收入为5000万美元。