Chang Yun Hsiang, Fujimori Yuma, Chen Cheng Chieh, Urabe Masayo, Karaki Taeko, Izumi Yusuke, Kaneko Kaoru, Mochiki Kisaragi
Janssen Pharmaceutical K.K., 3 Chome-5-2 Nishikanda, Chiyoda-ku, Tokyo, 101-0065, Japan.
Ther Innov Regul Sci. 2025 Jun 3. doi: 10.1007/s43441-025-00808-9.
Chimeric antigen receptor T-cell (CAR-T) therapy uses autologous T cells from patients to eliminate malignant targets. Cryopreservation of cellular starting materials, particularly fresh leukocytes, is an important step before production. While this promising specialized immune therapy is advancing, regulations have evolved, as specified in the US (21CFR1271) and Europe (EU Annex 1, 1394/2007). Cryopreservation is considered by this as minimal manipulation or is not considered as substantial manipulation unless there is alteration of relevant biological cell characteristics or cellular engineering. Similar consideration has been made by health authorities in Australia and South Korea. Conversely, the health authority in Japan determines if the starting material is applicable to Good Gene, Cellular, and Tissue-based Products Manufacturing Practice based on scientific data regarding the impact on product quality and safety. Whereas regulations have evolved in the US and EU, this is the first article to systemically review, from a manufacturer's perspective, the specific regulatory positions taken towards cryopreservation in Asia-Pacific (APAC) countries, i.e. Japan, Australia and South Korea. These positions generally consider that formulation and cryopreservation should be performed in a closed system, thus protecting cellular starting materials from contaminant exposure with a low-risk approach. Local and centralized cryopreservation logistics are discussed along with optimal implementation practices. The impact of geographic access on cryopreservation logistics, as well as the importance of careful evaluation of logistical and cost aspects for successful supply of CAR-T therapies in APAC, are also discussed.
嵌合抗原受体T细胞(CAR-T)疗法利用患者的自体T细胞来清除恶性靶点。细胞起始材料的冷冻保存,尤其是新鲜白细胞的冷冻保存,是生产前的重要步骤。在美国(21CFR1271)和欧洲(欧盟附件1、1394/2007)所规定的法规不断演变的情况下,这种有前景的特殊免疫疗法也在不断发展。在此,冷冻保存被视为最小程度的操作,或者除非相关生物细胞特性或细胞工程发生改变,否则不被视为重大操作。澳大利亚和韩国的卫生当局也有类似的考量。相反,日本的卫生当局根据关于对产品质量和安全性影响的科学数据来确定起始材料是否适用于良好基因、细胞和组织产品生产规范。鉴于美国和欧盟的法规已经演变,本文是第一篇从制造商的角度系统回顾亚太地区(APAC)国家,即日本、澳大利亚和韩国对冷冻保存所采取的具体监管立场的文章。这些立场通常认为配制和冷冻保存应在封闭系统中进行,从而以低风险方法保护细胞起始材料免受污染物暴露。文中还讨论了本地和集中式冷冻保存物流以及最佳实施做法。还讨论了地理可达性对冷冻保存物流的影响,以及仔细评估物流和成本方面对于在亚太地区成功供应CAR-T疗法的重要性。
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