China Implements New Standardization Guidelines for Radiopharmaceutical Production Effective March 2025

On March 1, 2025, the Guidelines for Inspection of Radiopharmaceutical Production (Trial) (hereinafter referred to as the “Guidelines”), issued by the Center for Special Drug Inspection of the National Medical Products Administration, officially came into effect, bringing new standards and guidance to the radiopharmaceutical production industry. The Guidelines aim to provide direction for on-site inspections of radiopharmaceutical production, fundamentally standardizing production processes. They apply to inspections of the radiopharmaceutical production phase, covering the entire process of production, testing, release, and distribution.

The Guidelines specify standardized requirements for all production processes, establishing specific inspection methods ranging from the procurement and storage of radiopharmaceuticals to their final dispensing. This not only helps enhance the professional competence of practitioners but also effectively reduces the impact of human factors on safety. The Guidelines will also strengthen the management of personnel, requiring nuclear medicine professionals to undergo specialized training and obtain certification before assuming their posts. The Special Drug Inspection Center of the National Medical Products Administration conducted extensive industry research and incorporated feedback from numerous experts in the field, ensuring that the Guidelines are highly feasible and scientifically sound. They will serve as a critical basis for regulatory inspections and provide clear direction for enterprises to improve their production management standards.

In recent years, the surging popularity of radiopharmaceuticals needs no elaboration.

On the market side,According to Grand View Research, the global market size for nuclear medicine was $8.1 billion in 2021 and is projected to grow at a compound annual growth rate (CAGR) of 13% from 2022 to 2030. The market size was approximately $8.9 billion in 2020 and is estimated to reach $24 billion by 2030. Among these regions, the Asia-Pacific region is the primary growth driver for the global radiopharmaceutical market, with China’s radiopharmaceutical market reaching RMB 5 billion in 2021. According to data from Peptide Research Society, China’s radiopharmaceutical market size reached RMB 6.15 billion in 2019, but declined during the pandemic in 2020 and 2021 to RMB 4.456 billion and RMB 5 billion, respectively.

At the clinical level,According to Frost & Sullivan data, as of October 2023, there were 64 approved radiopharmaceuticals globally, with a global R&D pipeline of 339 innovative radiopharmaceuticals. Innovative radiopharmaceuticals under development worldwide cover both diagnostic and therapeutic areas, with indications spanning multiple disease fields. In addition to oncology, these include mental disorders and autoimmune diseases. In China, 42 radiopharmaceuticals have been approved for marketing by the National Medical Products Administration (NMPA); however, most of these approved agents are generics that have been in clinical use for an extended period. Furthermore, there are 32 radiopharmaceuticals in China currently in clinical trials or at the stage of applying for market approval. Unlike the predominantly generic nature of already marketed products, the majority of radiopharmaceuticals under development are innovative, indicating rapid progress in the development of domestically originated innovative radiopharmaceuticals in China.

As public health awareness rises, the incidence of cancer and cardiovascular diseases in China is increasing. With innovative therapeutic radiopharmaceuticals successively entering the market, clinical demand for these products is growing year by year, driving an accelerated expansion of the market size.Despite the rapid growth of the radiopharmaceutical market, domestic production and distribution of radioactive drugs have historically faced numerous challenges. Due to the lack of a standardized system for graded management and research into related technical standards—such as those governing radiopharmaceutical transportation, cleanliness requirements at usage sites, and radiation protection—China had not previously established a nationwide, standardized distribution channel for radioactive drugs, which hindered their domestic production and circulation.

The pain points in the production, supply, and distribution of radiopharmaceuticals have long received significant attention at the policy level. In recent years, several landmark policies that sparked intense industry discussion have been released, addressing some of the challenges in areas such as medical isotope supply, radiopharmaceutical research and development, and clinical application barriers:

The “Outline of the ‘Healthy China 2030’ Planning,” issued by the Central Committee of the Communist Party of China and the State Council in 2016, proposed advancing the medical equipment industry, including diagnostic and testing equipment, and accelerating the development of medical isotopes. It further called for initiating the construction of one to two production reactors for medical isotopes by 2025, aiming to fundamentally reverse the situation where China’s supply of medical isotopes is dependent on foreign sources. In 2021, seven departments, including the China Atomic Energy Authority, the Ministry of Science and Technology, the Ministry of Public Security, the Ministry of Ecology and Environment, and the National Medical Products Administration, jointly released the “Medium- and Long-Term Development Plan for Medical Isotopes (2021–2035),” which set forth the goal of establishing a stable and self-reliant supply assurance system for medical isotopes.

With the rapid development of the radiopharmaceutical industry, the latest regulations introduced in this field demonstrate a trend toward increasingly detailed and clear regulatory oversight. The release of the "Guidelines for Inspection of Radiopharmaceutical Production (Trial)" fundamentally standardizes production processes. The Guidelines specify standardized requirements for each stage of production, establishing concrete inspection methods for every step from the procurement and storage of radiopharmaceuticals to their final distribution. These Guidelines will serve as a critical basis for regulatory authorities in conducting inspections and provide clear direction for enterprises to enhance their production management standards.

Due to their unique radioactivity, radiopharmaceuticals are subject to a safety licensing system across research and development, manufacturing, storage, sales, and transportation, similar to other radioactive sources. They must also comply with special regulations, including the Measures for the Administration of Radioactive Pharmaceuticals, the Law of the People’s Republic of China on Prevention and Control of Radioactive Pollution, the Regulations on Safety and Protection of Radioisotopes and Radiation-emitting Devices, the Measures for the Administration of Safety Licensing for Radioisotopes and Radiation-emitting Devices, the Regulations on the Safety Management of Transport of Radioactive Materials, and the Announcement of the National Medical Products Administration on Further Strengthening the Administration of Radioactive Pharmaceuticals.

In addition to the aforementioned basic provisions, the Guidelines further elaborate on various production aspects, including facilities and equipment for radiopharmaceutical manufacturing, production sites, quality control, and quality assurance.

With regard to the inspection of facility and equipment, the Guidelines impose stringent requirements on all areas, including the production area, warehousing area, quality control area, and auxiliary areas.In addition to complying with the Good Manufacturing Practice for Drugs (2010 Revision) and its relevant appendices, facilities of radiopharmaceutical manufacturers must also comprehensively address requirements such as radiation safety. During facility design, consideration should be given not only to the process-specific requirements for the facilities but also to the design and zoning of radiation work areas in accordance with environmental protection regulations. On-site inspections should primarily focus on radiation safety protection, containment against leakage, anti-theft measures, availability of appropriate monitoring instruments, measures to prevent contamination and cross-contamination, effective segregation between radioactive and non-radioactive work areas, and strict separation of operational areas for different radionuclides.

Regarding on-site production, given the unique nature and critical importance of radiopharmaceuticals, the Guidelines impose detailed requirements on every aspect, including personnel protection, material management, and production records.In particular, with regard to personnel safety, the Guidelines emphasize that enterprises should establish emergency response procedures and contingency plans for radioactive accidents in accordance with relevant regulatory requirements, conduct radiation dose monitoring for relevant personnel, and carry out occupational health examinations as mandated. Furthermore, the Guidelines separately list relatively common and representative radiopharmaceuticals used in radiotherapy (iodine [¹²⁵I] sealed seed sources), pharmaceuticals for in vivo diagnosis (technetium [^99mTc] Immediate Labeling of Drugs, Fluorine [¹⁸F] Deoxyglucose Injection), Reagents for In Vitro Diagnostic Use (Iodine[¹²⁵I] Key Points for Production Inspection of In Vitro Radioactive Diagnostic Kits, to Facilitate Rapid Reference and Implementation by Enterprises.

In terms of quality control, the Guidelines specify requirements for enterprises in multiple areas, including release testing capabilities, radiation safety licensing qualifications, instruments and equipment equipped with radiation protection devices, sampling and reserve samples, release of materials and products, ongoing stability testing of radiopharmaceuticals, and specific test items. The Guidelines also clearly define the educational background and qualification requirements for personnel in quality control laboratories.The head of the quality control laboratory shall possess sufficient qualifications and experience to manage the laboratory, hold a bachelor’s degree or higher in pharmacy or a related field, or hold an intermediate or higher professional technical title, and have expertise in nuclear medicine (pharmacy) or related fields as well as experience in the testing and management of radiopharmaceuticals. Inspection personnel in the quality control laboratory shall have at least a secondary vocational school or high school education in a related field, possess relevant professional knowledge of radiopharmaceuticals, and may only assume their posts after completing training appropriate to the position requirements and passing the corresponding assessments.

In terms of quality assurance, as this system is a critical safeguard for ensuring the consistent and stable quality of radiopharmaceuticals, the Guidelines set forth explicit requirements for its implementation, changes, deviations, corrective actions, and preventive actions. Overall, these requirements do not differ significantly from the quality assurance provisions applicable to the manufacturing processes of other pharmaceutical products.

Overall, the release of these Guidelines is highly significant. Although the intricate regulations further raise the already formidable barriers to entry in the radiopharmaceutical sector, they provide clear direction for high-quality radiopharmaceutical companies in the long run, accelerate the production and distribution of their products, and bring hope for patients to gain earlier access to high-quality, stable radiopharmaceuticals.

References:

① "Guidelines for the Inspection of Radiopharmaceutical Production (Trial)"
② Sullivan, “Blue Paper on the Current Status and Future Development of China’s Radiopharmaceutical Industry”

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