The role of investigator-initiated trials in advancing cell and gene therapy under China's dual-track regulatory system: Opportunities and challenges

Cell and gene therapy (CGT) technologies have significantly evolved in China, offering new treatment options for various incurable diseases. This study examines the role of Investigator-Initiated Trials (IIT) in the development of CGT products within China's unique dual-track regulatory system. Herein, we outline the three distinct phases of CGT development in China over the past 30 years, highlighting key milestones and regulatory shifts.The first stage (1991–2003) included the initiation of gene therapy research and approval of the world's first gene therapy product. The second stage (2003–2017) was marked by uneven development and a focus on clinical application, leading to controversies and regulatory changes. The third ongoing stage (2017–present) has been characterized by standardization and innovation, with significant advancements in CAR-T therapies and a surge in investigational new drug (IND) applications.China's dual-track system, which allows CGT to be regulated either as biologics or as medical technologies, has facilitated clinical research and introduced conflicts and challenges. While this system promotes innovation and expands patient access, it raises concerns regarding safety, efficacy, and quality control. Comparatively, the U.S. regulatory system primarily requires IND approval for most cell therapy clinical studies, highlighting differences in regulatory approaches.This study proposes refining the dual-track system and establishing a more transparent and efficient regulatory framework. Key measures include differentiating standards for distinct therapies, enhancing legal standardization, and integrating gene therapy research into the dual-track system. Together, these measures aim to balance innovation with safety, promoting the responsible development of CGT products in China.