Sasai Masao, Kitawaki Yayoi, Umezawa Akihiro, Oie Yoshinori, Kamiya Takahiro, Kawamura Takuji, Sato Yoji, Hosoya Satoshi, Sugawara Hiroyuki, Yamada Kazuto, Izumoto Hiroshi, Mae Yoshiyuki, Kuroda Tohru, Okada Kiyoshi
The University of Osaka Hospital, Osaka, Japan.
The Japanese Society for Regenerative Medicine, Tokyo, Japan.
Stem Cell Res Ther. 2025 May 13;16(1):238. doi: 10.1186/s13287-025-04343-0.
In recent years, therapeutic preparations using patient-derived tissues have emerged as commercially approved regenerative medicine products for expanding treatment possibilities for patients with no other treatment options. Autologous cell-processed products, derived from the tissue of the patient, typically exhibit variability in raw material quality, resulting in the generation of out-of-specification (OOS) products.
The compassionate use of OOS products is also practiced by the Food and Drug Administration and European Medicines Agency; differences among the three regulatory authorities were investigated to identify challenges in Japan. For conditions with no alternative treatments and severe time constraints, OOS products are sometimes used under compassionate grounds, particularly in Japan, where they are administered within the framework of clinical trials. This approach, although ethical, imposes significant operational and administrative burdens on medical institutions and marketing authorisation holders, raising concerns about sustainability. We considered the rationalisation of the current system and reached the conclusion that it would not contribute to load reduction and sustainability; thus, we devised a new framework.
This study reviewed the compassionate use systems for OOS products in Japan, the United States, and Europe, highlighting current challenges and proposing a sustainable regulatory framework for future practice.
近年来，使用患者来源组织的治疗制剂已成为商业上获批的再生医学产品，用于为没有其他治疗选择的患者扩大治疗可能性。源自患者组织的自体细胞处理产品通常在原材料质量上存在差异，导致产生不符合规格（OOS）的产品。
美国食品药品监督管理局和欧洲药品管理局也实行对不符合规格产品的同情用药；对这三个监管机构之间的差异进行了调查，以确定日本面临的挑战。对于没有替代治疗方法且时间紧迫的情况，有时会基于同情理由使用不符合规格的产品，特别是在日本，这些产品是在临床试验框架内给药的。这种方法虽然符合伦理，但给医疗机构和上市许可持有人带来了巨大的运营和行政负担，引发了对可持续性的担忧。我们考虑了当前系统的合理化，并得出结论认为这无助于减轻负担和实现可持续性；因此，我们设计了一个新的框架。
本研究回顾了日本、美国和欧洲对不符合规格产品的同情用药系统，强调了当前面临的挑战，并为未来实践提出了一个可持续的监管框架。
