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

Xiaodong Sun , Huixun Jia , Feng Qian , Bai Lu , Tien Yin Wong

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Vita > Expert Views > DOI: 10.15302/vita.2026.06.0048
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China’s investigator-initiated trials in cell and gene therapy

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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 20231 (Supplementary Fig. S1a). Currently, 73% of CGT candidates remain in the preclinical stage, with only 2% having advanced to Phase III trials and beyond1(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 IIT

China’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 development2.

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 mechanism3. 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 systems4. 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 IITs5. 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 activity, with registrations exceeding 40,000 by April 2026 according to Chinese Clinical Trial Registry (ChiCTR) statistics (available at the website of chictr.org.cn/searchproj). During the COVID-19 pandemic, emergency pathways demonstrated the system’s responsiveness: IIT data were accepted to support Investigational New Drug (IND) and New Drug Application (NDA) submissions; review timelines were shortened from 60 to 30 working days (and to 3 days for pediatric drugs); and rapid authorization was enabled for 5 COVID-19 vaccines, 11 therapeutics, and 128 diagnostic reagents6.

CHINA’S CURRENT CGT-FOCUSED IIT MODEL

Traditional IITs are often designed primarily for academic inquiry. By contrast, China’s CGT-focused IIT pathway has evolved into a translational development model with distinct practical advantages. In the US, FDA oversight of CGT follows a “product-based” framework7. IITs are generally categorized as either IND-IITs or non-IND-IITs: IND-IITs require an IND submission and stringent FDA oversight, whereas non-IND-IITs may proceed after institutional review; however, findings from non-IND-IITs intended for clinical translation must still enter the formal FDA approval pathway. In the European Union, clinical trials are governed by the Clinical Trials Regulation8, and IITs are primarily positioned as non-commercial academic research. Translating research findings into clinical application largely depends on the formal drug registration pathway, with substantial legal, administrative, and time burdens. In China, CGT-focused IITs are not intended to substitute for regulatory approval. Instead, they are designed to de-risk clinical development by rapidly assessing therapeutic activity and early safety in small patient cohort. They can address critical early questions, including indication selection, patient stratification, target engagement, and initial safety profiling. For example, in an IIT of autologous CiPSC-derived islet transplantation in patients with type 1 diabetes, Deng et al. reported insulin independence within two and a half months and sustained glycemic control for one year.9 Within this structured yet flexible framework, sponsors can generate high-quality human PoC data before committing to larger registrational programs, thereby improving the likelihood of success, shortening development timelines, and reducing costs.

CGT-focused IITs differ from traditional IITs in objectives, indication selection, and regulatory requirements (Table 1). Designated as an innovation priority and exemplar of “New Quality Productive Forces” by the Chinese government10, the CGT field has received policy support across different cities and provinces. Shanghai, one of China’s CGT leading hubs, has established an organizational structure for the CGT clinical research platform (Fig. 1a), as well as a clear application workflow (Fig. 1b) for CGT-IIT studies, which supports translation while enforcing rigorous standards. CGT IITs are restricted to qualified institutions, primarily tertiary hospitals certified by NMPA-GCP or institutions designated by the National Health Commission (NHC) for stem-cell clinical research, which must meet stringent infrastructure and expertise requirements. In recognition that conventional ethics committees are often inadequate for assessing the risks of advanced CGT therapies, the model establishes independent Multidisciplinary Scientific Review Committees, composed of CGT scientists, clinicians, and biostatisticians, to evaluate preclinical evidence, study design, and risk–benefit profiles. Independent data and safety monitoring boards provide real-time safety monitoring and continuous risk-benefit assessment, supported by transparent data platforms. The effectiveness of this framework is reflected in Shanghai’s record: as of Sep 2025, 4 of 9 NMPA-approved CGT products in China originated in Shanghai, and 25% of approved CGT clinical trials in China were being conducted there11. Representative successes include Legend Biotech's CAR-T therapy, whose IIT results showed an objective response rate of 88%12. This early-phase validation directly enabled a landmark collaboration with Janssen Pharmaceuticals, culminating in regulatory global approvals. Another IIT conducted at Shanghai Changzheng Hospital provided the first evidence that allogeneic anti-CD19 CAR-T cells could effectively treat patients with refractory and relapsed rheumatic immune diseases. All participants achieved complete B-cell depletion that was sustained for more than one year.13 Shanghai’s IIT pathway has also accelerated gene therapy development. Whereas voretigene neparvovec, an RPE65-targeted therapy, required 10 years from Phase I to US FDA approval14, Shanghai’s optimized IIT pathway enabled completion of all Phase I–III registration trials for a comparable inherited retinal disease target in just 3 years15.

This local experience is now entering a new stage of national policy consolidation. A pivotal development is the promulgation of the Regulations on Management of Clinical Research and Clinical Translational Application of Novel Biomedical Technologies (State Council Order No. 818), issued in Sep 2025 and effective from May 202616. More than a policy signal, this regulation establishes a national legal framework for NHC-supervised clinical research and translational application of novel biomedical technologies, including CGT interventions. It also clarifies how IIT data may inform translation and establishes a dual-track system for clinical translation: after completing clinical research, a new technology may either enter the traditional drug registration pathway or apply through the medical technology translation pathway. For CGT companies, this creates a more flexible “technology first, drug follow-up” strategy: IITs can provide lower-cost preliminary evidence of safety and efficacy, after which the appropriate registration route can be selected according to the nature of the technology. The two pathways are complementary and may substantially lower the threshold for translation. Notably, Order No. 818 also establishes, for the first time at the national level, a legal channel through which IIT-based translation may support compliant in-hospital charging. After a filed study demonstrates safety and efficacy, the technology may apply for regulated in-hospital charging, creating a “filing-translation-charging” loop. This is an important institutional innovation, with few direct international precedents.

Beyond regulatory flexibility, China’s CGT-focused IIT pathway is also being strengthened by an increasingly favorable investment ecosystem. China is moving beyond its earlier role as a “world factory” and is becoming a preferred destination for early CGT clinical validation. Order No. 818 creates a clearer route for research outputs to generate downstream translational and early commercial value. This institutional shift is attracting domestic and international capital to early CGT validation and clinical development in China. In 2025, investment has shifted markedly toward emerging therapeutic modalities such as CGT; these transactions accounted for nearly half of biopharmaceutical venture-capital activity, while the total value of innovative-drug license-out deals form China reached US$135.7 billion, with the CGT share contributed to rise17. A distinctive economic advantage of China’s CGT-IIT ecosystem lies in its ability to balance speed, quality, and cost-efficiency. Large patient populations support rapid enrollment, and the growing localization of the supply chain has reduced development costs. A particularly illustrative example is EsoBiotec, a Belgian biotechnology company that began with €22 million in seed funding and leveraged an approximately 8-month IIT conducted at Tongji Hospital in Wuhan18. It was later acquired by AstraZeneca in a transaction worth up to US$1 billion19. The case captures the economic logic of China’s IIT pathway: relatively modest early investment can be leveraged into substantial translational and commercial value.

CHINA’S FUTURE CGT-FOCUSED IIT: PATH FORWARDS AND CHALLENGES

Looking ahead, artificial intelligence (AI) may reshape CGT-focused IITs by enhancing efficiency, safety, and personalization across the development pipeline20. Advances in large language models and multimodal learning may help identify therapeutic targets, optimize gene-editing tools, and predict critical risks, including off-target effects and immune responses. These capabilities are particularly relevant for CGT, where safety and efficacy depend on target precision and minimization of immunotoxicity. In trial design, AI can support more flexible protocols, accelerate recruitment through electronic health records, and enable adaptive trials that incorporate real-time data. For safety and efficacy evaluation, AI can integrate multi-omics and clinical data to detect earlier risk, predict individual treatment responses, and support proactive monitoring and more personalized therapeutic strategies21.

As more CGT products enter clinical use, robust long-term follow-up and active post-marketing surveillance will be essential for ensuring durable safety and efficacy, and for maintaining public confidence. To this end, the NMPA has issued specific guidance on long-term follow-up for both gene therapy products and cell therapy products, requiring marketing authorization holders to conduct post-marketing studies and submit annual safety updates22. Post-approval oversight for CGTs in China increasingly also includes pharmacovigilance obligations and regulatory control over post-approval changes.

Despite the advantages, the IIT pathway faces substantial challenges due to inherent product risks, manifesting primarily as variation in professional capacity and review standards across centers, concerns over data reliability, limited post-trial patient access, ethical complexities surrounding informed consent, long-term uncertainty communication, public perception, and reconsent for follow-up studies. Importantly, China’s State Council Order No. 818, effective from May 202614, provides targeted measures to address these concerns: First, it establishes a “dual-review plus national filing” mechanism requiring qualified institutions to pass academic and ethics reviews and file with the NHC within five working days, while mandating retention of research records and source data for at least 30 years to strengthen traceability and data credibility; Second, it specifies that technologies proven safe and effective through IIT may, after approval, proceed to regulated clinical use, thereby accelerating patient access; Third, it is complemented by NHC guidance on informed consent for gene therapy trials that emphasizes clear communication of risks, uncertainties, and voluntariness, alongside recommendations for CGT centers to provide patient and family education, investigator training, community dialogue, and transparent adverse event report to build public trust and ensure ethical integrity throughout the research process23.

China has also emphasized alignment of its CGT regulatory framework with international standards. Since becoming a full member of the ICH in 201824, China has systematically implemented key ICH guidelines relevant to CGTs, including ICH E6(R3) on GCP, ICH E17 on multi-regional clinical trials, ICH E18 on genomic sampling, and ICH S12 on nonclinical evaluation of gene therapy products. For manufacturing quality, China is a candidate member of the Pharmaceutical Inspection Co-operation Scheme (PIC/S) and is aligning its GMP inspection standards with PIC/S requirements25. Meanwhile, China’s ethical framework for IITs remains broadly consistent with the Declaration of Helsinki and the guidelines of the Council for International Organizations of Medical Sciences. Together, these measures support the evolution of CGT-focused IITs from early translational research toward broader global development.

CONCLUSION

China’s CGT-focused IIT pathway illustrates how targeted policy support can establish coordinated translational mechanisms that balance regulatory oversight with innovation while ensuring patient safety. By combining qualified institutional capacity, staged scientific and ethics review, flexible translation pathways, and growing alignment with international standards, this model provides a potentially instructive blueprint for global CGT development.

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The Author(s) 2026. Published by Higher Education Press. This is an Open Access article distributed under the terms of the CC BY license (https://creativecommons.org/licenses/by/4.0/).

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Sun, X., Jia, H., Qian, F., Lu, B., Wong, T.  China’s investigator-initiated trials in cell and gene therapy  Vita https://doi.org/10.15302/vita.2026.06.0048 ()
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