Regulatory Science Study for Ensuring the Quality of Therapeutic extracellular vesicle（EV） Products Including Exosomes and Promoting Their Development

Therapeutic extracellular vesicle (EV) products, including those containing exosomes (hereinafter referred to as EV products), are expected to have potential as a new therapeutic modality. Many EV products are currently under development in Japan or other countries; however, there are no guidelines specific to this product category and there is a need for establishing regulatory requirements that supports product development. EVs have an extremely complex structure and show high levels of heterogeneity, and their mechanisms of action remain unclear. Additionally, because therapeutic EV products are often manufactured using cells, and it is difficult to sufficiently remove product- or process- related impurities during the purification process, thus posing challenges for impurity control. To ensure the quality of EV products, it is necessary to conduct sufficient characterization of EV products and to identify critical quality attributes that require control to ensure efficacy and safety. Thus, establishing a strategy for controlling the critical quality attributes within the intended limits, ranges, and distributions is key. Furthermore, it is important to set specifications to confirm that EV products of the intended quality have been obtained. This article describes the current state of research on establishing characterization methods for EV products, and recent topics related to quality issues that need to be considered for the development of therapeutic EV products.