The field of cell and gene therapy (CGT) is maturing at a rapid rate. Manufacturing remains a major challenge and manufacturing failures and limitations are a notable source of CGT products not meeting specification or being held back from regulatory approvals. To ensure that products remain compliant and competitive throughout their lifecycle, CGT process development requires both ongoing advancement of fit-for-purpose technologies to allow for and support well-designed development studies, and a methodology that enables these studies to occur effectively during focused product development campaigns. We describe a framework for ongoing innovation in CGT process development, manufacturing, and clinical testing, based on the quality by design (QbD) approach. We propose use of the concepts of process discovery, process characterization, and process development in an iterative way to refine the design space as a product matures. This strategy is enabled by the early implementation of broad and robust analytics, and a modular approach to accelerate optimization. With these strategies, CGT developers can prospectively plan for comparability studies and develop in a stage-appropriate manner, to allow for ongoing innovation and improvements from discovery through to commercialization.

中文翻译：

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细胞和基因治疗从发现到商业化的过程演变

细胞和基因治疗 (CGT) 领域正在迅速成熟。制造仍然是一个主要挑战，制造失败和限制是 CGT 产品不符合规范或无法获得监管批准的重要原因。为确保产品在整个生命周期内保持合规性和竞争力，CGT 工艺开发需要不断改进适合用途的技术以允许和支持精心设计的开发研究，以及使这些研究能够在重点产品期间有效进行的方法发展运动。我们描述了一个基于设计质量 (QbD) 方法的 CGT 工艺开发、制造和临床测试的持续创新框架。我们建议使用过程发现、过程表征、随着产品的成熟，以迭代的方式进行流程开发以完善设计空间。这一战略得益于广泛而强大的分析的早期实施，以及加速优化的模块化方法。通过这些策略，CGT 开发人员可以前瞻性地规划可比性研究并以适合阶段的方式进行开发，以允许从发现到商业化的持续创新和改进。