Continuation Application for the development of Integrated continuous and single-use (ICS) bioproduction platform (Phase IIB)

继续申请开发综合连续和一次性（ICS）生物生产平台（IIB期）

• 批准号: 10384023
• 负责人: Oleg Shinkazh
• 金额: $ 128.42万
• 依托单位: CHROMATAN CORPORATION
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10384023
• 关键词: 3D Print; Acceleration; Address; Antibodies; Antibody Therapy; Automation; Award; Biological Response Modifier Therapy; Biomanufacturing; Bioreactors; Bioterrorism; Books; Capital; Cell Line; Chromatography; Collaborations; Computer software; Crohn' s disease; Cyclic GMP; Data Set; Development; Devices; Documentation; Drug Evaluation; Economic Development; Economics; Equipment; Evaluation Research; Event; Funding; Generations; Goals; Growth; Industry; Joints; Laboratories; Letters; Life; Malignant Neoplasms; Manufacturer Name; Medicine; Membrane; Modeling; Monitor; Monoclonal Antibodies; National Institute of General Medical Sciences; Patients; Performance; Perfusion; Phase; Pilot Projects; Plant Resins; Procedures; Process; Production; Productivity; Progress Reports; Proteins; Research; Rheumatoid Arthritis; Risk; Running; Sales; Sampling; Savings; Site; Small Business Innovation Research Grant; System; Technology; Testing; Therapeutic; Thinness; Validation; Viral; Virus; Vision; Work; base; bioprocess; commercialization; cost; design; flexibility; innovation; meetings; monoclonal antibody production; next generation; novel; operation; pandemic disease; particle; pressure; programs; prototype; scale up; therapeutic protein

PROJECT SUMMARY / ABSTRACT The overall goal of the proposed Phase IIB 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 50% reduction in production costs for life saving therapies that treat conditions such as cancer, Crohn’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 2011 AAPS meeting: “It is predicted that manufacturing will change in the next 25 years as current manufacturing practices are abandoned in favor of cleaner, flexible, more efficient continuous manufacturing.” 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). CCTC has shown over 10X improvement in productivity vs. conventional columns with equivalent product quality in multiple pilot studies. Through our Phase II efforts the CCTC pilot system is now launched to the market with the first sale booked in 2021. We were also able to develop a 2nd generation flow path that will utilize 3D printed Dean Vortex Separators as well as specially developed large pore size membranes enabling long-term and fouling free operation of the ICS system. The Phase IIB effort will focus on finalizing the pilot scale integration of the ICS framework and scale up of the platform to cGMP. The program will be supported by multiple strategic partners – Proconex for automation, Purolite for resin manufacturing, and NewAge Industries for single-use and 3D printing. The project will also be supported by large biopharma players that have already invested into our technology – Merck, Roche and Takeda. Overall, commercialization of the ICS system will have the following impacts on bio-production: 1. Continuous operation will lead to lower capital cost and lower equipment footprint. 2. Single-use and closed system features will reduce capital cost, enable flexible manufacturing, and eliminate cleaning and cleaning validation requirements. 3. True steady state operation will enable in-line process monitoring of bioreactor and purification performance, leading to better robustness and product quality. 4. ICS flexibility will enable manufacturers to launch processes faster and at a lower cost resulting in better availability of life saving therapies to patients around the world. The ICS system will be a key component of the next generation vision we call NextGnBio – a quick-to-launch POD-like facility based on a joint vision with GCON. NextGnBio will save over 80% in capital, 50% in operating costs and enable a 50% acceleration of rapid scale up of life saving medicines.

项目总结/摘要 拟议的第IIB期SBIR项目的总体目标是将一种集成的 连续和一次性生物生产平台（ICS），实现灵活和稳健 治疗性蛋白质的制造。这种新型平台将实现连续的、一次性的、 治疗性蛋白质的低成本纯化。ICS系统的成功商业化将 导致至少50%的用于治疗病症的挽救生命疗法的生产成本降低 如癌症、克罗恩病和风湿性关节炎。 单克隆抗体和其他生物制品的连续灵活的一次性处理 治疗学已被确定为显著的未满足的需求。Janet Woodcock博士，主任 FDA药物评价和研究中心的负责人在2011年的AAPS会议上说：“这是 预测，制造业将在未来25年内发生变化， 被更清洁、更灵活、更高效的连续生产所取代。” 下游加工的重大瓶颈以及数量的爆炸性增长 开发中的治疗药物是这一未满足需求的主要驱动力。 ICS系统的目的是将两个最有前途的灵活和 市场上的连续技术-一次性灌注和新型一次性 纯化系统称为连续逆流切向色谱（CCTC）。 与传统色谱柱相比， 在多项中试研究中，产品质量相当。 通过我们的第二阶段努力，CTC试点系统现已推出市场， 销售于二零二一年预订。我们还能够开发第二代流路， 印刷的Dean涡旋分离器以及专门开发的大孔径膜 从而能够实现ICS系统的长期和无结垢操作。 第IIB阶段的工作将重点完成ICS框架的试点规模整合， 将平台扩大到cGMP。该计划将得到多个战略合作伙伴的支持- Proconex用于自动化，Purolite用于树脂制造，NewAge Industries用于一次性使用 和3D打印。该项目还将得到大型生物制药公司的支持， 投资于我们的技术-默克，罗氏和武田。 总体而言，ICS系统的商业化将对生物生产产生以下影响： 1.连续运行将导致更低的资本成本和更低的设备占地面积。 2.单次使用和封闭系统的特点将降低资本成本， 制造，并消除清洁和清洁验证要求。 3.真正的稳态操作将使得能够对生物反应器进行在线过程监测， 纯化性能，导致更好的鲁棒性和产品质量。 4. ICS的灵活性将使制造商能够以更低的成本更快地启动流程 从而使世界各地的患者更容易获得挽救生命的治疗。 ICS系统将成为我们称为NextGnBio的下一代愿景的关键组成部分- a 基于与GCON的联合愿景的快速发射POD式设施。下一篇GnBio将节省 80%的资本，50%的运营成本，并使生活的快速扩展加速50% 节约药品。