SBIR Phase I: Determine Performance Characteristics During Cultivation of Living Organisms in a Novel Single-Use Horizontal Modular and Pressurizable Microbial Fermentor

SBIR 第一阶段：确定新型一次性卧式模块化加压微生物发酵罐中活体培养过程中的性能特征

• 批准号: 2036270
• 负责人: Ernest Stadler
• 金额: $ 25.6万
• 依托单位: NEW HORIZON BIOTECH INC
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-15 至 2023-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2036270&HistoricalAwards=false
• 关键词: SBIR; Phase; Determine; Performance; Characteristics

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project is to significantly improve the ability to generate biological pharmaceuticals. The biopharmaceutical industry is working to grow specific genetically engineered microbial cells that will produce a vaccine, injectable protein, or other products. There is a pressing need to culture unique microbes, starting from small scale batches, that rapidly scale to commercially viable batch sizes with high product output. A pressurized horizontal fermentor supports the industry’s drive towards single-use bags for microbial fermentation, as single-use fermentors lower operating costs and reduce cross-contamination that can result in loss of an entire batch. This scalable, single-use fermentor should achieve higher yields and allow drug producers to produce kilogram quantities of protein in a more cost-effective manner. This innovative, flexible, pressurizable, horizontal modular design will decrease time-to-market for vaccines, therapeutic proteins or other microbially manufactured products, from both small and large biologics producers, to combat global infectious, and other diseases, at reduced operating costs, saving lives.The proposed project will advance the knowledge of how microbial cells are cultivated in a horizontal, pressurized single-use bag fermentor. The knowledge gained will validate microbial production using a modular design that provides flexibility to adjust the capacity of the system, without significant facility modifications or cost. An initial prototype demonstrated highly encouraging results regarding fast mixing times, proper scalable power input, and excellent oxygen mass transfer. The design to be refined here has the potential to transform the biologics manufacturing industry by impacting the ability to generate high cell densities and reduce the cost of microbial manufacturing. Research objectives are to demonstrate: a fully developed design with the heat removal capacity required of high cell density fermentation (currently unachievable using existing industry vertical single-use fermentor designs); a pressurized bag system that can achieve oxygen transfer rates needed for high density cultures; and a scalable format that allows for rapid scaling to 3000 liters. A fully functioning test fermentor will be built and evaluated using both computational fluid dynamics analysis and laboratory testing of culture conditions. Experimental work will evaluate high agitation impellers, high gas flows, gas sparger designs, and system structural elements.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

这项小型企业创新研究（SBIR）I阶段项目的更广泛的影响/商业潜力是显着提高生成生物制药的能力。生物制药行业正在努力发展特定的基因工程微生物细胞，该细胞将产生疫苗，可注射蛋白或其他产品。从小规模批次开始，迫切需要培养独特的微生物，从而迅速扩展到具有较高产品输出的商业可行批量尺寸。一个加压的水平发酵罐支持该行业朝着单利袋进行微生物发酵的动力，因为单利用发酵罐降低了运营成本并降低交叉污染，从而导致整个批次损失。这种可扩展的单利用发酵罐应达到更高的产量，并允许药物生产者以更具成本效益的方式生产千克量的蛋白质。这种创新，灵活的，可加压的水平模块化设计将降低疫苗，热蛋白或其他微生物制造产品的营销时间，从小型和大型生物制造商中，以抗击全球感染性和其他疾病，以降低的运营成本来抗衡，挽救了效率。获得的知识将使用模块化设计验证微生物生产，该模块化设计可灵活地调整系统的容量，而无需进行重大设施修改或成本。初始原型在快速混合时间，适当的可伸缩功率输入和出色的氧气传播方面表现出了极大的令人鼓舞的结果。这里要完善的设计有可能通过影响产生高细胞密度并降低微生物制造成本的能力来改变生物制造业。研究目的是证明：一种完全开发的设计，具有高细胞密度发酵所需的热量清除能力（目前使用现有的行业垂直单使用发酵罐设计无法实现）；可以实现高密度培养所需的加压袋系统；以及可扩展的格式，可快速扩展到3000升。使用计算流体动力学分析和培养条件实验室测试，将建立和评估功能齐全的试验器。实验性工作将评估高搅动叶轮，高气流，气体尖头设计和系统结构元素。该奖项反映了NSF的法定任务，并使用基金会的知识分子优点和更广泛的影响来评估，被认为是珍贵的支持。