Guidance on the clinical application of extracellular vesicles

Therapies using extracellular vesicles (EVs), exosomes, or cell culture supernatants containing EVs or exosomes (referred to as "EV therapies" in this Guidance) have garnered an increasing amount of interest. However, pharmaceutical products containing EVs as their main active ingredient are yet to receive regulatory approval. The "Basic points to consider regarding the preparation of extracellular vesicles and their clinical applications in Japan," was announced by the Japanese Society for Regenerative Medicine (JSRM) on March 10, 2021, with a specific focus on exosomes among EVs to promote high safety standards in this evolving field and facilitate the application of EV clinically. The Scientific Committee of the Pharmaceuticals and Medical Devices Agency and the Japanese Society for Extracellular Vesicles have issued reports and statements regarding treatment, resulting in a growing momentum toward treatment in Japan. This article summarized the basic items that should be recognized comprehensively for clinical practice in three categories: (1) risk profiling, (2) preparation (manufacturing) process and quality, and (3) verification of EVs checking items and effectiveness. This guideline will be revised in the future with technological innovations and new findings; nevertheless, it will serve as a guide for the development of treatments.