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: 10923587
• 负责人: Oleg Shinkazh
• 金额: $ 50.38万
• 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/10923587
• 关键词: 3D Print; Acceleration; Address; Antibodies; Automation; Biological Response Modifier Therapy; Bioreactors; Bioterrorism; Books; Capital; Chromatography; Crohn' s disease; Cyclic GMP; Development; Drug Evaluation; Equipment; Event; Generations; Goals; Growth; Industry; Investments; Joints; Life; Malignant Neoplasms; Manufacturer; Marketing; Medicine; Membrane; Monitor; Monoclonal Antibodies; Patients; Performance; Perfusion; Phase; Pilot Projects; Plant Resins; Process; Production; Productivity; Research; Rheumatoid Arthritis; Sales; Small Business Innovation Research Grant; System; Technology; Therapeutic; Validation; Vision; commercialization; cost; flexibility; improved; manufacture; meetings; next generation; novel; operation; pandemic disease; programs; 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.

项目摘要/摘要 拟议的第IIB期SBIR项目的总体目标是将集成的 连续和一次性使用的生物生产平台(ICS)，实现灵活和健壮 治疗性蛋白质的制造。这一新颖的平台将实现连续、一次性和 低成本纯化治疗性蛋白质。ICS系统的成功商业化将 使治疗疾病的救命疗法的生产成本至少降低50% 如癌症、克罗恩病和类风湿性关节炎。 连续灵活的单抗和其他生物制剂的一次性加工 治疗已被确定为一个重要的未得到满足的需求。珍妮特·伍德科克博士，主任 在2011年的一次AAPS会议上，FDA药物评估和研究中心的 预测制造业将在未来25年发生变化，就像当前的制造实践一样 都被抛弃了，取而代之的是更清洁、灵活、更高效的持续制造。 下游加工的重大瓶颈以及数量的爆炸性增长 开发中的许多治疗药物是这一未得到满足的需求的主要驱动力。 ICS系统的目的将是整合两个最有希望的灵活和 市场上的连续技术.一次性灌流和新型一次性使用 被称为连续逆流切向色谱(CCTC)的净化系统。 CCTC显示，与传统塔相比， 在多个试点研究中的同等产品质量。 通过我们第二阶段的努力，CCTC试点系统现在已经向市场推出了第一个 2021年预订的销售。我们还开发了第二代流道，它将利用3D 印制迪恩涡流分离器以及专门开发的大孔径膜 实现ICS系统的长期无污染运行。 第二阶段的工作将侧重于最终确定综合系统框架的试点规模整合，并 将平台向上扩展到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，这些公司已经 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.连续运行将降低资金成本和设备占用空间。 2.一次性使用和封闭的系统功能将降低资金成本，实现灵活 制造，并消除清洁和清洁验证要求。 3.真正的稳定运行将实现对生物反应器和 净化性能，导致更好的健壮性和产品质量。 4.ICS灵活性将使制造商能够以更快的速度和更低的成本推出流程 从而为世界各地的患者提供了更好的救命疗法。 ICS系统将是我们称为NextGnBio-a的下一代愿景的关键组件 基于与GCON的联合愿景的快速启动类似POD的设施。NextGnBio将节省 80%的资本，50%的运营成本，并实现50%的生命周期快速扩展 节省药品。