Center for Advanced Sensor Technology, Chemical and Biochemical Engineering Department, University of Maryland Baltimore County, Baltimore, MD, 21250, USA.
Microb Cell Fact. 2009 Aug 5;8:44. doi: 10.1186/1475-2859-8-44.
Upstream bioprocesses are extremely complex since living organisms are used to generate active pharmaceutical ingredients (APIs). Cells in culture behave uniquely in response to their environment, thus culture conditions must be precisely defined and controlled in order for productivity and product quality to be reproducible. Thus, development culturing platforms are needed where many experiments can be carried out at once and pertinent scale-up information can be obtained.
Here we have tested a High Throughput Bioreactor (HTBR) as a scale-down model for a lab-scale wave-type bioreactor (CultiBag). Mass transfer was characterized in both systems and scaling based on volumetric oxygen mass transfer coefficient (kLa) was sufficient to give similar DO trends. HTBR and CultiBag cell growth and mAb production were highly comparable in the first experiment where DO and pH were allowed to vary freely. In the second experiment, growth and mAb production rates were lower in the HTBR as compared to the CultiBag, where pH was controlled. The differences in magnitude were not considered significant for biological systems.
Similar oxygen delivery rates were achieved in both systems, leading to comparable culture performance (growth and mAb production) across scales and mode of mixing. HTBR model was most fitting when neither system was pH-controlled, providing an information-rich alternative to typically non-monitored mL-scale platforms.
上游生物工艺极其复杂，因为活性药物成分（APIs）是由活生物体生成的。培养中的细胞会根据其环境独特地表现，因此为了使生产力和产品质量具有重现性，必须精确定义和控制培养条件。因此，需要开发高通量生物反应器（HTBR）作为实验室规模波浪式生物反应器（CultiBag）的缩小模型。在这两个系统中都对传质进行了测试，基于体积氧传质系数（kLa）的缩放足以给出相似的 DO 趋势。在 DO 和 pH 可以自由变化的第一个实验中，HTBR 和 CultiBag 的细胞生长和 mAb 生产非常相似。在第二个实验中，与 pH 控制的 CultiBag 相比，HTBR 中的细胞生长和 mAb 生产速率较低。对于生物系统来说，这些差异的幅度并不被认为是显著的。
在这两个系统中都实现了相似的氧气输送速率，从而在不同的规模和混合模式下实现了相似的培养性能（生长和 mAb 生产）。当两个系统都没有进行 pH 控制时，HTBR 模型最适用，为通常非监测的 mL 规模平台提供了一种信息丰富的替代方案。
