Department of Biochemical Engineering, The Advanced Centre for Biochemical Engineering, University College London, Torrington Place, London, WC1E 7JE, UK.
Biotechnol Bioeng. 2014 Jan;111(1):69-83. doi: 10.1002/bit.25008. Epub 2013 Aug 16.
For allogeneic cell therapies to reach their therapeutic potential, challenges related to achieving scalable and robust manufacturing processes will need to be addressed. A particular challenge is producing lot-sizes capable of meeting commercial demands of up to 10(9) cells/dose for large patient numbers due to the current limitations of expansion technologies. This article describes the application of a decisional tool to identify the most cost-effective expansion technologies for different scales of production as well as current gaps in the technology capabilities for allogeneic cell therapy manufacture. The tool integrates bioprocess economics with optimization to assess the economic competitiveness of planar and microcarrier-based cell expansion technologies. Visualization methods were used to identify the production scales where planar technologies will cease to be cost-effective and where microcarrier-based bioreactors become the only option. The tool outputs also predict that for the industry to be sustainable for high demand scenarios, significant increases will likely be needed in the performance capabilities of microcarrier-based systems. These data are presented using a technology S-curve as well as windows of operation to identify the combination of cell productivities and scale of single-use bioreactors required to meet future lot sizes. The modeling insights can be used to identify where future R&D investment should be focused to improve the performance of the most promising technologies so that they become a robust and scalable option that enables the cell therapy industry reach commercially relevant lot sizes. The tool outputs can facilitate decision-making very early on in development and be used to predict, and better manage, the risk of process changes needed as products proceed through the development pathway.
为了使异体细胞疗法发挥其治疗潜力，需要解决与实现可扩展和强大的制造工艺相关的挑战。一个特别的挑战是生产能够满足高达 10（9）个细胞/剂量的商业需求的批量，因为目前的扩展技术存在限制。本文描述了应用决策工具来确定不同生产规模下最具成本效益的扩展技术，以及异体细胞疗法制造中当前技术能力的差距。该工具将生物工艺经济学与优化相结合，以评估平面和微载体细胞扩展技术的经济竞争力。可视化方法用于确定平面技术不再具有成本效益的生产规模，以及微载体生物反应器成为唯一选择的生产规模。工具输出还预测，为了使该行业能够满足高需求场景的要求，基于微载体的系统的性能能力可能需要显著提高。这些数据使用技术 S 曲线以及操作窗口呈现，以确定满足未来批量所需的细胞生产率和一次性生物反应器规模的组合。这些建模见解可用于确定未来研发投资应集中在何处，以提高最有前途的技术的性能，使其成为一种强大且可扩展的选择，使细胞治疗行业能够达到商业相关的批量。工具输出可以在开发的早期阶段非常有效地进行决策，并用于预测和更好地管理随着产品通过开发途径而需要进行的工艺变更的风险。
