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.

这个小企业创新研究（SBIR）第一阶段项目的更广泛的影响/商业潜力是显著提高生产生物药物的能力。生物制药业正在努力培育特定的基因工程微生物细胞，以生产疫苗、可注射蛋白质或其他产品。迫切需要培养独特的微生物，从小批量开始，迅速扩大到商业上可行的批量和高产品产量。加压水平发酵罐支持行业向一次性袋微生物发酵的驱动，因为一次性发酵罐降低了运营成本，减少了可能导致整个批次损失的交叉污染。这种可扩展的一次性发酵罐应该可以实现更高的产量，并允许药品生产商以更具成本效益的方式生产公斤数量的蛋白质。这种创新、灵活、可加压的横向模块化设计将缩短小型和大型生物制剂生产商生产的疫苗、治疗性蛋白质或其他微生物制造产品的上市时间，以降低运营成本，抗击全球传染病和其他疾病，从而挽救生命。拟议的项目将推进如何培养微生物细胞的知识在一个水平，加压一次性袋发酵罐。所获得的知识将验证微生物生产使用模块化设计，提供灵活性来调整系统的容量，不需要重大的设施修改或成本。最初的原型在快速混合时间，适当的可扩展功率输入和出色的氧传质方面表现出非常令人鼓舞的结果。这里要改进的设计有可能通过影响产生高细胞密度和降低微生物制造成本的能力来改变生物制剂制造行业。研究目标是证明：一个完全开发的设计，具有高细胞密度发酵所需的除热能力（目前使用现有的行业垂直一次性发酵罐设计无法实现）；一种加压袋系统，可实现高密度培养所需的氧传递速率；还有一个可扩展的格式，可以快速扩展到3000升。将建立一个功能齐全的试验发酵罐，并使用计算流体动力学分析和培养条件的实验室测试进行评估。实验工作将评估高搅拌叶轮、高气体流量、气体分离器设计和系统结构要素。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。