Myles Lequina, Church Terry David
Department of Regulatory and Clinical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California, USA.
Cytotherapy. 2022 Mar;24(3):344-355. doi: 10.1016/j.jcyt.2021.09.012. Epub 2021 Nov 6.
The novelty of cell and gene therapies (CGTs) has introduced unique supply chain challenges and considerations not seen by chemically synthesized (small-molecule) drugs. These complexities increase during the clinical phases, where drug safety and efficacy milestones are still underdeveloped. For example, for autologous therapies such as chimeric antigen receptor T-cell therapies, in which the treatment is developed from the patient's own cells, supply chain management plays an integral role in chemistry, manufacturing and control processes. Supply chain management requires proactive planning because of the strict cold chain requirements and time sensitivity of CGTs. This research examines strategies and responses to challenges experienced by industry stakeholders (e.g., sponsors and manufacturers) during the implementation phases of clinical supply chain management. This research further evaluates the adequacy of the current regulatory framework for distribution and supply chain management of CGTs in the US.
A survey methodology was used to query subject matter experts from the biopharmaceutical industry who were familiar with the clinical supply management of CGTs in the US. The survey instrument was developed using an implementation framework and disseminated electronically to mid- and senior-level subject matter experts who had experience with clinical trials, supply chain management and CGTs.
A total of 128 respondents accessed the survey, and 105 respondents answered at least one question. Seventy-five respondents completed the survey. Results showed that a lack of harmonization in regulations across the supply chain, limited resources, challenges with vendor management, high costs and complexities in the supply chain due to product specificity and customization proved to be impediments for the industry. In addition, the coronavirus disease 2019 pandemic had a significant impact on supply chain implementation. The results revealed that less than half of the respondents had business continuity plans in place. These challenges increased for smaller and mid-size organizations. Thirty percent of small and mid-size organizations were less prepared to scale up than larger companies.
Suggestions from industry stakeholders were to adopt and enforce Good Distribution Practices in the US (81%), pre-plan distribution strategies with internal and external stakeholders along the supply chain and develop agile systems and robust processes end to end. Hurdles in scaling up and scaling out from the clinical to commercial phases for time- and temperature-sensitive CGT products make it difficult to predict the supply chain's long-term feasibility. Although there are initiatives to improve these impediments, such as improving industry partnerships and creating global CGT transportation standards, there are still regulatory knowledge gaps present for CGTs. Therefore, it is essential to establish a baseline and foundation for CGT supply chains extending beyond the loading dock.
细胞与基因疗法（CGT）的创新性带来了独特的供应链挑战与考量，这是化学合成（小分子）药物所没有的。这些复杂性在临床阶段会增加，因为药物安全性和有效性的里程碑仍不完善。例如，对于嵌合抗原受体T细胞疗法等自体疗法，治疗是从患者自身细胞开发而来，供应链管理在化学、制造和控制过程中起着不可或缺的作用。由于CGT对冷链要求严格且时间敏感，供应链管理需要积极规划。本研究探讨了行业利益相关者（如申办者和制造商）在临床供应链管理实施阶段所面临挑战的应对策略。本研究还进一步评估了美国现行CGT分销和供应链管理监管框架的充分性。
采用调查方法，询问来自生物制药行业、熟悉美国CGT临床供应管理的主题专家。调查工具基于一个实施框架开发，并以电子方式分发给有临床试验、供应链管理和CGT经验的中高级主题专家。
共有128名受访者访问了该调查，105名受访者至少回答了一个问题。75名受访者完成了调查。结果显示，供应链法规缺乏协调性、资源有限、供应商管理存在挑战、成本高昂以及由于产品特异性和定制导致的供应链复杂性，对该行业构成了阻碍。此外，2019冠状病毒病疫情对供应链实施产生了重大影响。结果显示，不到一半的受访者制定了业务连续性计划。对于中小型组织而言，这些挑战更为严峻。30%的中小型组织在扩大规模方面比大型公司准备更不足。
行业利益相关者提出的建议包括在美国采用并执行良好分销规范（81%），与供应链上的内部和外部利益相关者预先规划分销策略，并端到端地开发敏捷系统和稳健流程。对于对时间和温度敏感的CGT产品，从临床阶段扩大到商业阶段时，扩大规模和扩大范围存在障碍，这使得难以预测供应链的长期可行性。尽管有举措改善这些障碍，如加强行业伙伴关系和制定全球CGT运输标准，但CGT仍存在监管知识差距。因此，为超越装卸平台的CGT供应链建立基线和基础至关重要。
