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: 10596522
• 负责人: Oleg Shinkazh
• 金额: $ 70.73万
• 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 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10596522
• 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; Economics; Equipment; Event; Funding; Generations; Goals; Growth; Industry; Investments; Joints; Laboratories; Letters; Life; Malignant Neoplasms; Manufacturer; Marketing; 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; Site; Small Business Innovation Research Grant; System; Technology; Testing; Therapeutic; Thinness; Validation; Viral; Virus; Vision; Work; bioprocess; commercialization; cost; design; flexibility; improved; innovation; integration site; manufacture; 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.

项目概要/摘要 拟议的 IIB 期 SBIR 项目的总体目标是将集成的商业化 连续和一次性生物生产平台 (ICS)，灵活且稳健 治疗性蛋白质的制造。这个新颖的平台将实现连续、一次性和 治疗性蛋白质的低成本纯化。 ICS系统的成功商业化将 使救生疗法的生产成本降低至少 50% 例如癌症、克罗恩病和类风湿性关节炎。 单克隆抗体和其他生物制品的连续、灵活的一次性处理 治疗已被确定为一个重大的未满足的需求。珍妮特·伍德科克博士，主任 FDA 药物评价和研究中心的主任在 2011 年 AAPS 会议上表示：“这是 预测制造业将在未来 25 年内改变当前的制造实践 被抛弃，取而代之的是更清洁、灵活、更高效的连续制造。” 下游加工瓶颈明显，数量爆发式增长 开发中的治疗方法是这种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——一次性灌注和新颖的一次性使用 纯化系统称为连续逆流切向色谱法 (CCTC)。 CCTC 的生产率比传统色谱柱提高了 10 倍以上 多项试点研究中具有同等的产品质量。 经过我们第二阶段的努力，CCTC 试点系统现已推向市场，并推出了首个 预订于 2021 年销售。我们还能够开发利用 3D 的第二代流程 印刷 Dean Vortex 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。 IIB 阶段的工作重点是完成 ICS 框架的试点规模整合和 将平台扩展到 cGMP。该计划将得到多个战略合作伙伴的支持—— 用于自动化的 Proconex、用于树脂制造的 Purolite 以及用于一次性使用的 NewAge Industries 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. 连续运行将降低资本成本和设备占地面积。 2. 一次性使用和封闭系统的特点将降低资金成本，实现灵活 制造，并消除清洁和清洁验证要求。 3. 真正的稳态运行将实现生物反应器的在线过程监控和 净化性能，带来更好的稳健性和产品质量。 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 从而为世界各地的患者提供更好的救生疗法。 ICS 系统将成为下一代愿景的关键组成部分，我们称之为 NextGnBio – 基于与 GCON 的共同愿景，快速启动类似 POD 的设施。 NextGnBio 将节省超过 80% 的资本，50% 的运营成本，并使生命周期的快速扩大加速 50% 节省药品。