A Parallel Regulatory Pathway for New Microbial Technologies in China: Distinct From Drugs and Devices

Keywords

microbiota transplantation / new biomedical technologies / oncolytic bacteria / oncolytic therapy / oncolytic virus / phage therapy / regulation

From May 1, 2026, China officially implemented the Regulations on Administration of Clinical Research and Clinical Translational Application of New Biomedical Technologies (State Council Decree No. 818, hereafter Decree No. 818), promulgated by the State Council of China. Under Decree No. 818, the new biomedical technologies (NBT) are managed in parallel with drugs and medical devices. This new pathway represents a pioneering institutional design [1].

Over the past decades, China has steadily advanced the reform of the review and approval system for pharmaceuticals and medical devices, which has markedly improved the research, development, and manufacturing quality of China's biomedical industry, laying a solid foundation for the compliant development of cutting-edge technologies [2]. Decree No. 818 marks a landmark reform in China's biomedical regulatory system and constitutes a major achievement in China's continuous improvement of biomedical regulatory governance.

Decree No. 818 establishes a list-based management system for the NBT, allowing dynamic adjustment of technical entries by the state according to technological developments. The first edition of the New Biomedical Technologies List (NBT List) covers the NBT including new gene therapy, new cell therapy, new tissue and organ therapy, new microbial therapy, and brain-computer interface technologies [1].

Under Decree No. 818, the National Health Commission (NHC) of China, in collaboration with the National Medical Products Administration (NMPA), formulated the Guiding Principles for the Classification of New Biomedical Technologies and Drugs/Medical Devices (Interim) [1], clarifying the boundaries between new microbial therapy technologies and drugs or medical devices, particularly for technologies that resist standardization as drugs or devices and exhibit high personalization. For technologies in the clinical research phase, the NHC formulates and dynamically adjusts the Filing Guidance List for Clinical Study on New Biomedical Technologies, guiding sponsor institutions to independently determine technology classification and complete filing in accordance with applicable regulations. In the clinical translation phase, approval is limited to highly personalized technologies for which no drugs with the same mechanism of action have been marketed or have entered confirmatory clinical trials, and to rare disease technologies lacking drugs with the same mechanism for the same indication. Decree No. 818 establishes a priority review and approval pathway for new microbial therapy technologies intended to treat life-threatening diseases lacking effective treatment options and for those urgently needed in public health. Decree No. 818 prohibits both clinical research sponsors and institutions from charging study participants for NBT during the clinical research phase. Medical institutions may charge for these therapies only after the technology has been approved for clinical translation and application and the institution meets the prescribed conditions for implementation.

Decree No. 818 establishes a new governance framework for new microbial therapy technologies, providing a new optional regulatory approval pathway tailored to the personalized, diverse, and clinically dependent nature of microbial therapies. The inaugural list encompasses three categories of new microbial therapy technologies [1], defined as follows: (1) New oncolytic microbial therapy technologies: technologies that employ natural or genetically engineered oncolytic viruses or bacteria to selectively infect and kill tumor cells, while activating T cells and other immune cells to elicit sustained antitumor responses. (2) New phage therapy technologies: technologies that employ bacteriophages to eliminate pathogenic bacteria for the treatment of infectious diseases. (3) New microbiota transplantation technologies: technologies involving the transplantation of uncultured functional microbiota from healthy donors, or isolated and cultured single-strain or defined mixed-strain preparations, into the human body via oral, endoscopic, enema, or other routes (with or without genetic modification of the transplanted microorganisms) to alter local microbiota composition and function, thereby reconstructing the microecological environment. The NBT List explicitly stipulates that microbiota transplantation technologies solely limited to the isolation or acquisition of microbiota from the feces of healthy donors without further processing are excluded from this regulatory category.

New microbial therapy technologies represented by oncolytic virus technology, oncolytic bacteria technology, phage technology, and microbiota transplantation (including engineered bacteria technology and selective microbiota technology) are characterized by a high degree of personalization and difficulty in standardizing industrial production, making them incompatible with the traditional regulatory systems for pharmaceuticals and medical devices [3]. Under the conventional regulatory model, such technologies have long been confronted with ambiguous translational pathways, slow clinical transformation, and high compliance costs, leaving numerous innovative technologies unable to achieve clinical translation from the laboratory bench to the bedside.

Microbiota transplantation technologies encompass fecal microbiota transplantation (FMT), vaginal microbiota transplantation, engineered bacteria therapy, and selective formulated microbiota therapy. FMT, the most established microbiota transplantation modality, has a global research and application foundation. China's approach to FMT regulation exemplifies the divergence between China and other countries. Under Decree No. 818, FMT is explicitly excluded from the scope of NBT because the NHC has already authorized it as a clinical technology. Although FMT is not currently covered by China's basic medical insurance scheme, it is reimbursed by certain commercial insurance plans that complement national basic medical insurance.

In the United States, the Food and Drug Administration (FDA) adopts a dual-track regulatory system. It permits FMT to be used as a medical technology within a narrow scope for the treatment of recurrent Clostridioides difficile infection. Meanwhile, for such microbial consortia that cannot be fully manufactured in a highly industrialized manner, the FDA has approved related products such as REBYOTA and VOWST [3, 4]. China has approved medical devices to support the technical procedures of FMT, yet no FMT-based pharmaceutical products have been approved to date.

China has adopted a relatively lenient regulatory environment for FMT, creating valuable opportunities for its application in the treatment of various refractory and critical illnesses. Nevertheless, some commercial companies have taken advantage of this situation to establish stool banks, selling stool preparations to hospitals and patients and even promoting such services to beauty institutions. A similar phenomenon also existed in the United States before the FDA imposed strict regulation on FMT in May 2013. In May 2025, a panel of Chinese experts developed professional recommendations for the research, development, and regulation of FMT [5].

The global regulatory evolution of biological materials such as blood, bone, sperm, and eggs indicates that nearly all jurisdictions have historically faced challenges related to inadequate traceability, incomplete donor screening, and insufficient bio-vigilance, which may raise potential risks to patient safety. Eventually, almost all countries have moved toward rigorous governmental oversight. Therapeutic stool banks will inevitably follow the same regulatory trajectory, and strengthened supervision is merely a matter of time. In light of safety concerns and the need to standardize clinical application, it is now imperative for China to establish formal legislation governing FMT.

China and the United States adopt distinct regulatory frameworks in the field of microbial therapy. China has established a new regulatory model jointly led by the NHC and the NMPA. For highly personalized microbial therapy technologies that are difficult to standardize, the NHC grants approval via the regulatory pathway for the NBT. The review focuses on the safety, efficacy, and multicenter reproducibility of the technology, as well as the qualifications of medical institutions and practitioners, standard clinical procedures, hierarchical risk control, and full-cycle reassessment.

For standardizable and industrializable microbial therapy products, the NMPA oversees the approval process. The two pathways are clearly defined, mutually complementary, and seamlessly interconnected. By contrast, the FDA primarily classifies microbial therapies as drugs or biologics, with core requirements centered on Good Manufacturing Practice (GMP)-compliant manufacturing, standardization, and quality control. Additionally, the FDA offers flexible regulatory pathways for breakthrough gene-editing technologies. The FDA recently issued draft guidance enabling sponsors of targeted individualized therapies to generate substantial evidence of effectiveness and safety when randomized controlled trials are not feasible due to small patient populations [6].

Decree No. 818 and associated administrative rules implement risk-graded management for NBT [1], requiring periodic safety data reporting and triggering reevaluation when necessary to ensure controlled technology rollout (Table 1). Decree No. 818 stipulates that clinical application of high-risk, medium-risk, and low-risk technologies shall be restricted for five, three, and one year(s) following approval, respectively, to medical institutions that have participated in the relevant clinical research and meet the requisite conditions. Upon expiration of the applicable period, if no adverse events or uncontrollable risks have occurred or if reevaluation confirms that benefits substantially outweigh risks, other qualified medical institutions may conduct clinical application subject to record-filing.

The implementation of Decree No. 818 provides a transformative impetus for microbiota medicine in China. The cutting-edge technologies that were previously difficult for clinical implementation, such as phage therapy, customized microbiome intervention, and engineered bacteria therapy, will gain a clear legal pathway and become viable for translation from bench to clinic. New development opportunities have emerged in the fields of drug-resistant bacterial infections and rare diseases. Clear regulatory frameworks will draw commercial capital, talent, and technologies into the microbial medicine sector, fostering an innovative industrial chain encompassing microbial resource exploration, strain modification, formulation development, clinical translation, and scalable manufacturing. Furthermore, Decree No. 818 emphasizes the protection of research participants' rights and interests. It mandates that research institutions conduct rigorous ethical review and standardize participant recruitment, while explicitly prohibiting any fees charged to participants for clinical research, thereby further ensuring the standardized and ethical advancement of emerging microbial therapies.

Decree No. 818 establishes a new governance framework for microbial therapies. At present, microbial medicine is undergoing rapid development worldwide, yet regulatory systems in most countries suffer from inadequate adaptability. The traditional pharmaceutical regulatory model is inflexible and unable to keep pace with the trend of personalized medicine; some countries lack dedicated regulatory provisions, resulting in market disorder and significant safety risks. By establishing a dual-track system that distinguishes between (1) standardized products regulated as drugs or devices under the NMPA and (2) individualized NBT overseen by the NHC, China balances innovation efficiency and patient safety while accommodating the characteristics of microbial therapies.

Overall, the field of microbiota medicine depends on sustained technological innovation to ensure its sustainable advancement. To support the development of new microbial therapies, China has established a distinct regulatory pathway, separate from those for drugs and medical devices. Under Decree No. 818, these therapies are expected to accelerate clinical translation and expand treatment options for patients with conditions that are difficult to address through conventional pharmaceuticals.

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© 2026 The Author(s). Microbiota Medicine Research published by John Wiley & Sons Australia, Ltd on behalf of Higher Education Press.