SBIR Phase I: Novel compact cell settlers for high cell density perfusion cultures of mammalian cells

SBIR 第一期：用于哺乳动物细胞高密度灌注培养的新型紧凑型细胞定居器

• 批准号: 1648370
• 负责人: Dhinakar Kompala
• 金额: $ 22.5万
• 依托单位: Sudhin Biopharma Company
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1648370&HistoricalAwards=false
• 关键词: SBIR; Phase; Novel; compact; cell

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project is the development of a novel compact cell settler that can selectively remove dead cells and cell debris from the cell culture broth and completely recycle all the live and productive cells back to the continuous perfusion bioreactor. As this membrane-free device is not prone to clogging like the competing membrane-based cell retention devices, a single perfusion bioreactor culture does not need to be terminated prematurely after 3 or 4 weeks (due to accumulation of dead cells and cell debris resulting in reduced product quality and clogged membranes in current devices). The novel compact cell settler has a small size and footprint compared with other cell retention devices, and increases the likelihood of wider adaptation of the technology by a larger number of biomanufacturing companies and reduces the cost of manufacture of therapeutic biologics. As biosimilar price competition is expected for successful products that are coming off patent protection, reducing the cost of their manufacture using superior cell culture techniques will enable increased affordability of these drugs to a wider patient population. This SBIR Phase I project proposes to develop a novel compact and more efficient method of scaling up inclined settler technology, which has been scaled up inefficiently as rectilinear lamellar settlers. While a few biological manufacturers have successfully adapted the protruding lamellar settlers to manufacture therapeutic biologics from recombinant mammalian cells in high cell density perfusion bioreactors, the proposed novel compact cell settler is predicted to achieve the required separation of dead cells and cell debris from a high cell density perfusion bioreactor with a much smaller footprint compared to the original inclined lamellar settler design. Three key objectives for the research are to 1) demonstrate that the novel compact cell settler can achieve and maintain high viable cell densities indefinitely, 2) determine the maximum perfusion rate that maintain the high viable cell density indefinitely for smaller settlers of two different sizes, and 3) develop new scaling laws that can predict the size requirements of the settlers for larger commercial-scale bioreactors. These objectives will be accomplished by a systematic experimental plan to investigate the performance of the novel settlers at two different sizes and for two different mammalian cell types.

这项小型企业创新研究（SBIR）项目的更广泛的影响/商业潜力是开发新型紧凑型细胞定居者，可以选择性地从细胞培养汤中清除死细胞和细胞碎屑，并将所有活细胞和生产性细胞完全回收回连续的灌注生物反应器。 由于该无膜装置不容易像竞争性的基于膜的细胞保留装置那样堵塞，因此3或4周后，不需要过早地终止单个灌注生物反应器培养物（由于死亡细胞和细胞碎屑的积累，导致产品质量降低，并且在当前设备中堵塞了膜）。 与其他细胞保留装置相比，新型紧凑型细胞定居者的尺寸和占地面积很小，并且通过大量的生物制造公司增加了对技术更广泛适应的可能性，并降低了治疗生物制造的制造成本。 由于预计成功的产品竞争会产生专利保护的成功产品，因此使用卓越的细胞培养技术降低了其制造成本，将使这些药物的负担能力提高到更广泛的患者人群。这个SBIR I期项目提议开发一种新颖的紧凑，更有效的方法来扩展倾斜的定居者技术，该技术已被缩放为直线层状定居者的效率低下。 虽然一些生物制造商已经成功地适应了伸出的层状定居者，以在高细胞密度灌注生物反应器中从重组哺乳动物细胞中生产治疗性生物学，但预计提出的新型新型紧凑型细胞定居者可预测将死细胞和细胞脱发与较小的较小的较小的细胞分离的分离量相结合，使其与较小的细胞分离量相结合。 设计。研究的三个关键目标是1）证明，新型紧凑型细胞定居者可以实现并维持高可行的细胞密度，2）确定最大灌注率无限期地维持高可行的细胞密度，对于两个不同尺寸的较小尺寸的较小尺寸的较小的定居者和3）开发新的缩放定律，以预测较大的商业商业尺寸的新规模规律，以预测较大的商业尺寸的尺寸要求。 这些目标将通过系统的实验计划来实现，以研究两种不同尺寸和两种不同哺乳动物细胞类型的新型定居者的性能。