【1】Bacterial resistance has become a global public health event
He pointed out that bacterial resistance has become a global public health event and is expected to directly lead to 39 million deaths and economic losses of hundreds of billions of dollars from 2025 to 2050. Phage therapy that can accurately kill bacteria is the most reliable and disruptive method.
Currently, the United States, Europe, South Korea, Australia and other countries are accelerating the deployment of clinical guidelines, standards and even phage therapy drug and technology approvals to occupy this cutting-edge field. Although my country has many bright spots in scientific research, it lacks unified quality standards for phage preparations, and the approval path and requirements for clinical application of phages are still unclear.
He analyzed the current specific dilemma and current situation.
(1) Quality standards: There is a gap from "group standards" to "national standards".
At present, my country lacks GMP facilities for human phage preparations, and phage therapy-related companies are all in the start-up stage and generally lack the funds and capabilities to build GMP. The Shanghai Pharmaceutical Industry Association released the "Quality Requirements for Therapeutic Phage Preparations" group standard in 2024, which is currently the only domestic standard. However, this standard only requires the quality of the final product, and there is still a lack of guidance standards for the quality requirements and control of the entire process. There is an urgent need to promote the construction of higher-level standards.
(2) Approval path: There is a gap between policy dividends and implementation details.
The State Food and Drug Administration's "Draft for Comment on Advanced Therapeutic Drugs" includes gene-editing phages, and registration guidelines for new phage therapy technologies will also be issued under the framework of the upcoming Order 818. These top-level signals are extremely forward-looking.
However, the specific approval path is still in a fuzzy area and needs to be clarified urgently. Internationally, Belgium, France and Portugal have successively approved personalized treatments according to the EU local preparation route. Australia plans to grant a 2-year GMP exemption period to personalized and phage preparations in the clinical research stage. These adaptive ideas urgently need to be transformed and absorbed in light of our national conditions.
【2】Standards first, path pilot, industry cultivation
Zhu Tongyu said that in order to break the above-mentioned bottlenecks and avoid falling behind, a three-in-one promotion strategy of "standards first, path pilots, and industry cultivation" will be adopted to seize the commanding heights of the industrialization of phage therapy. Specific suggestions are as follows:
(1) Promulgate the "Technical Guiding Principles for Quality Control of Therapeutic Phage Preparations" as soon as possible.
It is recommended that the "Technical Guiding Principles for Quality Control of Therapeutic Phage Preparations" be issued as soon as possible based on the published Shanghai group standards, absorb European experience. Clarify the core requirements for phage selection, production and quality control, and provide a unified yardstick for the development and testing of phage products.
In view of the safety characteristics of bacteriophage, such as specific sterilization and no direct toxicity to eukaryotic cells, it is recommended that personalized phage preparations and formula products with low safety risks that are urgently needed for clinical use should be allowed to be produced by institutions that meet the corresponding biosafety and cleanliness conditions and used within the framework of ethical review and emergency treatment filing. A GMP exemption period of 2-3 years or simplified certification should be piloted. At the same time, companies are required to use the exemption period to accelerate the construction of GMP facilities and pilot "stepped GMP"
(2) Implement classified management and issue review guidelines.
1. Establish a dual-track system with parallel “drug pathways” and “technical pathways”. It is recommended that the State Food and Drug Administration draft and publish the "Technical Guiding Principles for Phage Drug R&D and Review". Clearly incorporate phage fixed formulas into the management of biological products, and clarify the inclusion conditions and licensing policies for advanced therapeutic drugs; personalized preparations that are "matched according to the patient's bacterial type" will be registered and transformed in accordance with the 818 new biomedical technology.
2. Rely on Order 818 to open up a fast channel for the transformation of new technologies. It is recommended that clinical transformation guidelines be formulated as soon as possible. For those whose preliminary clinical research results have met the transformation conditions, they can directly apply for transformation applications. It is allowed to establish regional phage diagnosis and treatment centers in tertiary hospitals and regional medical centers under the 818 framework to carry out standardized and scalable personalized treatments. Clarify charging standards, medical insurance access and post-transformation supervision responsibilities, so that policy dividends can be implemented into clinical tools.
(3) Innovate organizational mechanisms and form working groups.
It is recommended that the National Health Commission take the lead, cooperate with the Food and Drug Administration, the Ministry of Science and Technology and other departments, as well as research, clinical and commercial institutions, to establish a "phage therapy collaborative working group" composed of experts in "regulatory science + clinical medicine + microbiology + pharmaceutical engineering" to establish and upgrade my country's internal regulatory science think tank, hold regular consultations, and coordinate to solve cross-departmental problems such as GMP certification, medical insurance coding, and price declaration.
Phage therapy is a strategic pivot to address biosecurity challenges and develop biomedicine. The unformed international supervision is a window period for my country to take the lead. Through upgrading standards, piloting flexible policies and cross-departmental collaboration, we can find a path to high-quality development of phage therapy that is in line with national conditions.
Reporting from Beijing by Jiupai News special correspondent Li Yang
Editor Wu Diwu Feifei
