Weng Lindong
Novo Nordisk Research Center Seattle, Inc., United States.
J Pharm Sci. 2023 Oct;112(10):2615-2620. doi: 10.1016/j.xphs.2023.08.001. Epub 2023 Aug 6.
Cell therapy uses living cells as a drug to treat diseases. To develop a cell therapy drug product (DP), cryopreservation plays a central role in extending the shelf life of these living medicines by pausing their biological activities, especially preventing degradation, at a temperature as low as liquid nitrogen. This helps overcome the temporal and geographical gaps between centralized manufacturing and clinical administration, as well as allowing sufficient time for full release testing and flexibility in scheduling patients for administration. Cryopreservation determines or influences several key manufacturing, logistical, or clinical in-use processes, including formulation, filling, controlled rate freezing, cryogenic storage and transportation, thawing, and dose preparation. This article overviews the key technical aspects of cell therapy DP development and elucidates fundamental principles of cryobiology that should be considered when we design and optimize the relevant processes. This article also discusses the challenges that motivate continued innovation for cell therapy drug product development.
细胞疗法使用活细胞作为药物来治疗疾病。为了开发细胞治疗药物产品（DP），冷冻保存通过在液氮温度下暂停其生物活性，特别是防止降解，在延长这些活体药物的保质期方面发挥着核心作用。这有助于克服集中生产和临床给药之间的时间和地理差距，也为全面放行测试留出足够时间，并在安排患者给药方面提供灵活性。冷冻保存决定或影响几个关键的生产、物流或临床使用过程，包括配方、灌装、程序降温冷冻、低温储存和运输、解冻以及剂量制备。本文概述了细胞治疗药物产品开发的关键技术方面，并阐明了在设计和优化相关过程时应考虑的低温生物学基本原理。本文还讨论了推动细胞治疗药物产品开发持续创新的挑战。
