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: 8591579
• 负责人: Oleg Shinkazh
• 金额: $ 59.51万
• 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 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8591579
• 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 II期提案要求为色谱公司提供985,000美元的资金，用于扩大和商业化连续逆流切向色谱（CCTC），用于纯化高价值生物制品，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容量有限和费用高昂，细胞培养技术的最新进展造成了“下游瓶颈”。CCTC通过将树脂颗粒以浆液的形式泵入由一系列静态混合器和中空纤维膜模块组成的一次性流道，克服了传统柱色谱法的许多局限性。CCTC系统消除了耗时且劳动密集的柱填料。系统组件更便宜，线性可扩展，可用于大规模系统的完全一次性流道设计。这对于生产临床产品批次或在多产品设施中使用特别有吸引力，例如与一次性生物反应器结合使用。本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，我们将在早期采用者的工艺开发实验室（富士Diosynth和Regeneron）测试CCTC alpha系统的性能，从而改进该技术。在第二年，该公司将扩大技术规模，使其能够在临床cGMP环境下加工至少1公斤的单克隆抗体。色谱公司认为，CCTC技术将为色谱的大规模商业应用带来以下有利影响：？与柱色谱法相比，树脂体积要求减少10倍？一次性流动路径，消除了昂贵的清洗、清洗验证和柱填料？简单的可扩展性和纯化高达1公斤MAB的能力？在大规模运营中大幅减少资本投资（80%），采用“量入为出”的剃刀/刀片设计。降低资本风险。？ 临床捕获色谱的下游处理成本显著节省（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众健康，这两者都将导致药品成本的降低。克劳兰预计这将是第五年的市场