Regulation of exosomes as biologic medicines: Regulatory challenges faced in exosome development and manufacturing processes.

With advances in medical technology, extracellular vesicles, also known as exosomes, are gaining widespread attention because of their potential therapeutic applications. However, their regulatory landscape is complex and varies across countries because of their unique intracellular mechanisms of action. The diversity of manufacturing techniques renders their standardization challenging, leading to a fragmented regulatory landscape. The current global regulatory framework of exosomes can be broadly classified into two strategies: one involves elucidating constituent components within exosomes and the other involves examining the physiological repercussions of their secretion. When using exosomes as therapeutic agents, they should be governed similarly to biological medicinal products. Similar to biologics, exosomes have been analyzed to determine their particle size and protein composition. An exosome-based therapeutic agent should be clinically approved after understanding its molecular composition and structure and demonstrating its pharmacokinetics and therapeutic efficacy. However, demonstrating the pharmacokinetics and therapeutic efficacy of exosomes is challenging for regulatory agencies. This article reviews the technical characteristics of exosomes, analyzes the trends in regulatory laws in various countries, and discusses the chemistry, manufacturing, and control requirements of clinical applications.

Perspectives on Challenges to Cell Therapy Development in Taiwan: Strengthening Evidential Standards and Ways Forward.

Over the past years, the field of regenerative medicine and cell therapy has garnered much interest, extending beyond the bench to broader use, and commercialization. These therapies undergo stringent regulatory oversight as a result of their complexities and potential risk across different jurisdictions. Taiwan's government, with the aim of developing the country as a hub for regenerative medicine in Asia, enacted a dual track act to promote the development of regenerative and cell therapy products. This qualitative study used purposive sampling to recruit sixteen experts (Twelve respondents from medical institutions and four respondents from the industry) to understand their perspectives on one of the regulatory tracks which governs the medical use of cell technologies and challenges regarding its implementation. Semi-structured interviews were conducted, transcribed, coded and thematically analyzed. Three major themes emerged from the analysis: 1) Perceptions of the "Special Regulation for Cell Therapy" 2) Emerging issues and controversies on the medical use of cell technologies in private clinics, and 3) Challenges impeding the clinical innovation of cell technologies. As reported by the experts, it was clear that the special regulation for cell therapy was aimed at legalizing the clinical use of cell therapy in a similar fashion to an evidence-based pathway, to promote clinical innovation, ensure manufacturing consistency, and improve oversight on cell-based therapies. Thus, the regulation addresses the issues of safety concerns, patient's access and stem cell tourism. However, the limited approved cell techniques, quality control during cell processing, time, and criteria used in evaluating applications in addition to the need to develop evidential standards for clinical evidence are some of the difficulties faced. Thus, policy interventions on funding, educational resources, training, and regulatory clarity addressing these challenges may positively impact clinical innovation of cell therapy in Taiwan.

Adoption of Regulations for Cell Therapy Development: Linkage Between Taiwan and Japan.

Although cell-based therapy has become a promising treatment, its practice and evaluation process remain unstandardized. Therefore, Japan initiated a dual-track regulatory framework for cell-based therapy aiming to promote and regulate the therapies to ensure that patients can access safe and effective treatments. Influenced by such pathway, Taiwan adopted the framework and initiated its own cell-based therapy regulation in 2018. This paper discusses how Japan has influenced Taiwan in developing regulations for cell-based therapy.