Regulatory advancements in Japan's conditional and time-limited approval scheme for regenerative medical products: the first guidance on the approval scheme and the second review for full approval of the first conditional and time-limited approved cellular product, HeartSheet

Abstract

In Japan, the Act on Securing Quality, Efficacy, and Safety of Products including Pharmaceuticals and Medical Devices (PMD Act) provides the option for an expedited approval scheme, conditional and time limited, for regenerative medical products only. In March 2024, the Guidance for Conditional and Time-Limited Approval for Regenerative Medical Products and the Development of Subsequent Efficacy Evaluation Plan was established by the Ministry of Health, Labor and Welfare (MHLW). This document is the first guidance on the approval scheme, providing information such as specific examples of the scope of this scheme as well as an indication of what should be considered in the post-marketing approval condition assessment. HeartSheet—a human (autologous) skeletal myoblast-derived cell sheet—was the first product approved through the conditional and time-limited approval scheme. After the second review by the Pharmaceuticals and Medical Devices Agency (PMDA) based on post-marketing data, the MHLW decided in July 2024 that the product had not demonstrated efficacy and that full approval was not appropriate. This is the first time that post-marketing data have been considered for the full approval of a conditional and time-limited approval product. This decision demonstrates that the conditional and time-limited approval scheme is strictly enforced. This article describes key points of the guidance on the conditional and time-limited approval scheme and the PMDA's full approval review experience with HeartSheet. These regulatory actions will further deepen the understanding of the conditional and time-limited approval scheme, especially among developers, and promote more appropriate use of the scheme.