Marcus Center for Therapeutic Cell Characterization and Manufacturing, Parker H. Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA; School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, USA; NSF Engineering Research Center (ERC) for cell Manufacturing Technologies (CMaT), USA.
H. Milton Stewart School of Industrial and Systems Engineering, Atlanta, GA, USA.
Cytotherapy. 2024 Sep;26(9):967-979. doi: 10.1016/j.jcyt.2024.03.011. Epub 2024 Apr 4.
Although several cell-based therapies have received FDA approval, and others are showing promising results, scalable, and quality-driven reproducible manufacturing of therapeutic cells at a lower cost remains challenging. Challenges include starting material and patient variability, limited understanding of manufacturing process parameter effects on quality, complex supply chain logistics, and lack of predictive, well-understood product quality attributes. These issues can manifest as increased production costs, longer production times, greater batch-to-batch variability, and lower overall yield of viable, high-quality cells. The lack of data-driven insights and decision-making in cell manufacturing and delivery is an underlying commonality behind all these problems. Data collection and analytics from discovery, preclinical and clinical research, process development, and product manufacturing have not been sufficiently utilized to develop a "systems" understanding and identify actionable controls. Experience from other industries shows that data science and analytics can drive technological innovations and manufacturing optimization, leading to improved consistency, reduced risk, and lower cost. The cell therapy manufacturing industry will benefit from implementing data science tools, such as data-driven modeling, data management and mining, AI, and machine learning. The integration of data-driven predictive capabilities into cell therapy manufacturing, such as predicting product quality and clinical outcomes based on manufacturing data, or ensuring robustness and reliability using data-driven supply-chain modeling could enable more precise and efficient production processes and lead to better patient access and outcomes. In this review, we introduce some of the relevant computational and data science tools and how they are being or can be implemented in the cell therapy manufacturing workflow. We also identify areas where innovative approaches are required to address challenges and opportunities specific to the cell therapy industry. We conclude that interfacing data science throughout a cell therapy product lifecycle, developing data-driven manufacturing workflow, designing better data collection tools and algorithms, using data analytics and AI-based methods to better understand critical quality attributes and critical-process parameters, and training the appropriate workforce will be critical for overcoming current industry and regulatory barriers and accelerating clinical translation.
尽管已有几种基于细胞的疗法获得了 FDA 的批准,还有一些疗法显示出很有前景的结果,但以更低的成本实现治疗性细胞的可扩展、质量驱动和可重复制造仍然具有挑战性。挑战包括起始材料和患者变异性、对制造工艺参数对质量影响的有限理解、复杂的供应链物流以及缺乏可预测、充分理解的产品质量属性。这些问题可能表现为增加生产成本、延长生产时间、批次间变异性更大以及可存活的高质量细胞的总体产量降低。细胞制造和交付中缺乏数据驱动的见解和决策是所有这些问题背后的一个共同根本原因。从发现、临床前和临床研究、工艺开发和产品制造中收集的数据和分析尚未充分用于开发“系统”理解并确定可操作的控制措施。其他行业的经验表明,数据科学和分析可以推动技术创新和制造优化,从而提高一致性、降低风险和降低成本。细胞治疗制造行业将受益于实施数据科学工具,例如数据驱动的建模、数据管理和挖掘、人工智能和机器学习。将数据驱动的预测能力集成到细胞治疗制造中,例如根据制造数据预测产品质量和临床结果,或使用数据驱动的供应链建模确保稳健性和可靠性,可以实现更精确和高效的生产流程,并带来更好的患者可及性和结果。在这篇综述中,我们介绍了一些相关的计算和数据科学工具,以及它们如何或可以在细胞治疗制造工作流程中实施。我们还确定了需要创新方法的领域,以解决细胞治疗行业特有的挑战和机遇。我们的结论是,在细胞治疗产品的整个生命周期中连接数据科学、开发数据驱动的制造工作流程、设计更好的数据收集工具和算法、使用数据分析和基于人工智能的方法更好地理解关键质量属性和关键工艺参数,以及培训合适的劳动力将是克服当前行业和监管障碍并加速临床转化的关键。