Challenges and opportunities in the compassionate use of out-of-specification products in autologous regenerative medicine.

Background: 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.

Main body: 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.

Conclusion: 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.