Ancillary materials (AMs) play a critical role in the manufacture of cell and gene therapies, and best practices for their quality management are the subject of ongoing discussion. Given that the final product cannot be sterilized, AM quality becomes increasingly critical to the clinical advancement of cell and gene therapies. Despite a lack of direct legislative direction regarding AM quality, internationally harmonized guidance is available from several industry-standard bodies that describe the principles and application of a risk-based approach to AM qualification and related supply-chain risk management. According to a best-practice risk-based approach, AMs must be adequately qualified to a degree that reflects the level of risk the material presents to patient safety and the drug product's specification. This general approach can be implemented in different ways, and balancing quality with cost of goods is critical to the cost-effective manufacture of advanced therapy medicinal products. In some cases, it may be preferable or necessary to use AMs that are produced in compliance with current Good Manufacturing Practice. However, developers may be able to suppress manufacturing costs without undermining safety or regulatory compliance in the case that a material presents a lower risk profile. Despite a great deal of attention and interest in the quality of AMs in the cell and gene therapy space, there is still a need for greater harmonization to create a shared understanding of what constitutes a risk-based approach to AM production and sourcing. In this article, we propose a staged approach to AM quality that achieves a balance between the competing demands of risk mitigation and cost of goods containment at the various stages of AM quality development. Our novel, heuristic framework for communication among AM suppliers, users and regulators aims to bring down development and manufacturing costs and lessen the workload around regulatory compliance.

中文翻译：

---

建立一个通用框架来定义整个开发范围内的辅助材料质量

辅助材料 (AM) 在细胞和基因疗法的制造中发挥着关键作用，其质量管理的最佳实践是持续讨论的主题。鉴于最终产品无法灭菌，AM 质量对细胞和基因疗法的临床进展变得越来越重要。尽管缺乏关于 AM 质量的直接立法指导，但可以从几个行业标准机构获得国际统一的指导，这些机构描述了 AM 资格和相关供应链风险管理的基于风险的方法的原则和应用。根据基于风险的最佳实践方法，AM 必须在一定程度上充分合格，以反映材料对患者安全和药品规格带来的风险水平。这种通用方法可以通过不同方式实施，平衡质量与商品成本对于先进治疗药物的成本效益制造至关重要。在某些情况下，最好或有必要使用符合当前良好生产规范生产的 AM。但是，在材料风险较低的情况下，开发人员可能能够在不破坏安全性或法规遵从性的情况下抑制制造成本。尽管在细胞和基因治疗领域对 AM 的质量引起了极大的关注和兴趣，但仍然需要加强协调，以形成对基于风险的 AM 生产和采购方法构成的共同理解。在本文中，我们提出了一种分阶段的 AM 质量方法，在 AM 质量发展的各个阶段，在风险缓解和货物控制成本的竞争需求之间实现平衡。我们用于 AM 供应商、用户和监管机构之间沟通的新颖启发式框架旨在降低开发和制造成本，并减少监管合规方面的工作量。