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：向NIH提交的SBIR第二阶段提案要求为Chromatan，Inc.提供985，000美元的资金。为了扩大和商业化用于纯化高价值生物产品的连续逆流切向色谱（CCTC），例如，用于治疗癌症和关节炎的单克隆抗体。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。该系统消除了柱填料，这是耗时和劳动密集型。系统组件便宜得多，并且线性可扩展，从而能够实现用于大规模系统的完全一次性流动路径设计。这对于临床产品批次的生产或用于多产品设施，例如，与一次性生物反应器组合。拟议研究的总体目标是设计、构建和验证首个cGMP CCTC系统。在第一年，我们将通过在我们的早期采用者- Fujifilm Diosynth和Regeneron的工艺开发实验室测试CCTC α系统的性能来完善该技术。在第二年，Chromatan将扩大技术规模，以便能够在临床cGMP环境中处理至少1 kg单克隆抗体。Chromatan预计，CCTC技术将为色谱的大规模商业应用提供以下有利影响：10-与柱色谱法相比，树脂体积要求降低了1倍？一次性流路，无需昂贵的清洁、清洁验证和色谱柱填充？简单的可扩展性和纯化高达1 kg MAB的能力？大规模运营中的资本投资显著减少（80%），采用剃刀/剃刀刀片设计的“按需付费”方法。降低资本风险。?临床捕获色谱法的下游处理成本显著降低（65%）。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预测第五年市场 渗透率为10%，收入为5000万美元。