China’s investigator-initiated trials in cell and gene therapy

Cell and gene therapy (CGT), at the cutting edge of biomedicine, treats genetic disorders, refractory cancers, and rare diseases by modifying cellular or genetic material.The global CGT pipeline steadily expanded from 2015 to 2023 1 (Supplementary Fig. S1a).Currently, 73% of CGT candidates remain in the preclinical stage, with only 2% having advanced to Phase III trials and beyond 1 (Supplementary Fig. S1b).This skewed distribution underscores the urgent need for more efficient regulatory frameworks.In response to these challenges, China has developed strategic policies, notably a unique Investigator-Initiated Trial (IIT) pathway, to accelerate CGT development.As global pharmaceutical and biotech companies increasingly turn to China to leverage its robust basic research ecosystem, the IIT pathway has emerged as a cornerstone of the country's strategy to foster innovation, expedite early clinical proof-of-concept (PoC), mitigate investment risk, and reduce development costs for CGT.In this paper, we review the developmental history of IIT in China, and the status and future directions of IIT for CGT. HISTORICAL PERSPECTIVE OF CHINA'S IITChina's IIT system has evolved over three decades through distinct regulatory phases.The initial Good Clinical Practice (GCP) guidelines, published in 1998, did not distinguish between IITs from industry-sponsored trials (ISTs), and IITs were conducted sporadically in research hospitals.In 2003, an approval quota system introduced an 18-24-month waiting period and substantially constrained IIT development 2 .A major turning point came in 2015, when the National Medical Products Administration (NMPA, then known as CFDA) abolished the quota system and implemented a 60-day default approval mechanism 3 .In parallel, the Ministry of Science and Technology of China launched a program to establish National Clinical Medicine Research Centers, aiming to integrate clinical research platforms and strengthen ethical review systems 4 .In 2021, the "Measures for the Administration of Investigator-Initiated Trials (Trial Implementation)" provided, for the first time at the national level, a systematic regulatory framework for IITs 5 .This measure enabled academic investigators and biopharmaceutical companies to conduct IITs under institutional review board (IRB) approval and International Council for Harmonisation (ICH)-GCP standards.The reforms drove a substantial expansion of IIT activ-