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National Standard Interpretation: GB 18280.1—2025 "Sterilization of Health Care Products — Radiation — Part 1: Requirements for Development, Validation and Routine Control of a Sterilization Process for Medical Devices"
I. Background and Significance of the Standard Revision The release of GB 18280.1—2025 marks the completion of a comprehensive technical revision of the core standard regulating the development, validation, and routine control of radiation sterilization processes since the previous GB 18280.1—2015. Managed by the National Technical Committee 200 on Disinfection Technology and Equipment (SAC/TC 200), this standard is modified to adopt the international standard ISO 11137-1:2025, systematically coordinating and unifying the international application framework for radiation processing requirements. The standard specifies the development requirements for sterilizing medical devices using gamma rays, electron beams, and X-rays, the validation and revalidation requirements for the sterilization process, the routine control and release requirements, as well as the requirements for maintaining the continued effectiveness of the sterilization process.
Since the release of GB 18280.1—2015, the technological landscape of radiation sterilization has undergone profound changes: the supply of Cobalt-60 (60Co) radioactive sources has remained continuously tight, and the safety control of radiation source protection has become increasingly stringent. On the other hand, high-power industrial electron accelerators and high-energy X-ray (bremsstrahlung) target conversion technologies have rapidly matured. Furthermore, empirical research advances in radiation biology and dosimetry indicate that several prescriptive clauses in the 2015 version (such as fixed dose audit cycles and upper threshold limits for accelerator energy) can be updated to align with the new industry situation without reducing the Sterility Assurance Level (10^-6 SAL).
By embedding risk management concepts, refining process control requirements, and adding normative references, this standard introduces industry best practices for medical device manufacturers and radiation processing enterprises. Compared to the 2015 version, the main changes are as follows.
II. Main Contents of the Standard Revision
(1) Increase in Energy Threshold for Accelerator-Induced Radioactivity Assessment GB 18280.1—2025 formally raises the upper energy limits for accelerator devices used in the sterilization of medical products in Chapter 5 (Characterization of the Sterilizing Agent) and Chapter 6 (Special Description of Process and Equipment). - The maximum permissible nominal energy for electron beam devices is increased from 10 MeV to 11 MeV. - The maximum permissible nominal energy for electron beam devices used for X-ray target conversion (bremsstrahlung) is increased from 5 MeV to 7.5 MeV. The 2025 version specifies the corresponding thresholds for assessing induced radioactivity: within the revised limits, when processing with standard medical device constituent materials, there is no need to assess induced radioactivity.
The energy limits set in the old version (10 MeV for electron beams, 5 MeV for X-rays) originated from conservative assessments of induced radioactivity research in the 1980s. Over the following decades, the International Atomic Energy Agency (IAEA), national metrology institutes, and industry working groups have conducted extensive collaborative research, systematically evaluating the threshold energies, activation cross-sections, and isotope yields for all common medical polymers and metals (including titanium, stainless steel, and cobalt-chromium alloys), thereby updating the energy thresholds for induced radioactivity.
(2) Normative Integration of ISO 13004:2022 Chapter 8 (Process Definition) of GB 18280.1—2025 integrates the relevant requirements of ISO 13004:2022 ("Sterilization of health care products — Radiation — Substantiation of a selected sterilization dose: The VDmaxSD method"). In the 2015 version, sections 8.2 and GB 18280.2—2015 only recognized two options for substantiating the sterilization dose: VDmax25 (corresponding to a 25 kGy sterilization dose) and VDmax15 (corresponding to a 15 kGy sterilization dose). ISO/TS 13004:2013 was published as a technical specification, providing substantiation doses in 2.5 kGy increments (e.g., 17.5, 20.0, 22.5, 27.5, 30.0, 32.5, and 35.0 kGy). However, because it lacked formal international standard status, it was not widely recognized by regulatory bodies. The 2025 revised standard directly incorporates the substantiation doses of the VDmax method from ISO 13004:2022 into the standard's process specification system.
The foundation of the VDmax method lies in confirming that the radiation resistance of the natural bioburden on medical products is equal to or lower than the Standard Distribution of Resistance (SDR). For a given average bioburden (x̄), the method applies a verification dose (VDmax) to the microbial population to substantiate whether the target Sterility Assurance Level of 10^-1 can be achieved.
Previously, when manufacturers proved their products had low bioburden (e.g., an average bioburden of 10 CFU), the only standardized options available were: - Adopting the VDmax25 method, where even if the dose guaranteed to achieve a 10^-6 SAL was significantly lower than 25 kGy, the minimum routine processing dose still had to be set at 25 kGy. - Adopting Method 1 or Method 2 specified in GB 18280.2, which requires a large number of samples (e.g., over 100 items per batch, across multiple batches), multiple sterility tests, and complex fractional dose experiments. - Utilizing ISO/TS 13004 to substantiate VDmax17.5 or VDmax20, which faced regulatory resistance due to its lack of widespread acceptance.
The key technical driver for this revision is that forcing radiation-sensitive polymers, bioconjugates, electronic sensor modules, and combination drug-device products into the more conservative 25 kGy dose category can lead to potential polymer degradation, free radical generation, yellowing, delamination, and loss of functionality. Incorporating ISO 13004:2022 into the GB 18280.1 framework provides statistical and microbiological support for substantiating doses that align with the actual microbial contamination risk of the products.
(3) Cross-Modal and Cross-Facility Transfer of Sterilization and Verification Doses Section 8.4 of this standard introduces clear, standardized rules to regulate the transfer of established doses across different radiation facilities and different radiation modalities. - 8.4.1 specifies the transfer requirements for the maximum acceptable dose (Dmax,acc). - 8.4.2.1 allows the transfer of verification doses or established sterilization doses to a radiation source different from the original one (e.g., transferring between Cobalt-60 gamma rays, electron beams, and X-rays, or between different commercial radiation facilities), provided the product does not contain liquid water. - 8.4.2.2 stipulates that for products containing liquid water, transfer is prohibited unless specific data demonstrate that differences in operating conditions between the two radiation sources (such as dose rate, temperature, etc.) have no adverse effect on the lethality.
Article 8.4 addresses a long-standing controversy in the industrial sterilization and microbiology industries: whether radiation-induced microbial death is dependent on the irradiation modality. For dry medical products (solid plastics, metals, ceramics, dry diagnostic test strips, non-hydrated fabrics), the microbial inactivation mechanism is dominated by the direct action of ionizing radiation on microbial DNA and cellular structures. Whether the primary ionizing particles are secondary Compton electrons induced by Cobalt-60 (gamma ray) photons, secondary photoelectrons/Compton electrons induced by bremsstrahlung (X-rays), or primary relativistic electrons generated by the accelerator beam, the energy deposition per unit mass (1 Gy = 1 J/kg) produces equivalent direct ionization. Extensive data accumulated from decades of industrial validation confirm that for the bioburden of dry products, the average lethal dose (D10 value) remains constant across gamma rays, electron beams, and X-rays.
For products containing liquid water (prefilled syringes, hydrogels, liquid culture media, hydrated ophthalmic suspensions), the microbial inactivation mechanism is largely mediated by the indirect effects of liquid water radiolysis, producing reactive oxygen species (ROS), including hydroxyl radicals (OH·), hydrated electrons [e⁻(aq)], hydrogen radicals (H·), and hydrogen peroxide (H₂O₂). The generation, diffusion kinetics, and recombination rates of these radiolysis products are highly sensitive to the following factors: - Dose rate: The instantaneous dose rate of electron beam systems (10⁶–10⁸ Gy/s) is several orders of magnitude higher than that of gamma irradiation facilities (1–10 kGy/min). High free radical density favors radical-radical recombination (e.g., OH + OH → H₂O₂) rather than diffusion-limited DNA attack. - Dissolved oxygen consumption: High dose rates rapidly consume dissolved oxygen in the liquid microenvironment, causing transient local hypoxia and altering microbial radiation sensitivity.
Therefore, this standard sets a clear boundary: doses can be freely transferred between validated radiation sources for dry products, whereas products containing liquid water require rigorous equivalence studies on the bactericidal mechanism.
(4) Changes in Dose Audit Frequency In Chapter 12 (Maintenance of Process Effectiveness), the requirements for the continuous verification of sterilization doses have been updated: - Section 12.1.3 of the 2015 version required sterilization dose audits to be strictly executed every 3 months, unless the cycle could be extended with a comprehensive bioburden history and documented justification. - The 2025 version adjusts the audit baseline: the interval for sterilization dose audits can be extended up to 4 months, provided that at least 4 audits are completed within each 12-month calendar cycle.
Additionally, Chapter 12 of the 2025 version clarifies the expected requirements for bioburden determination, directly linking the frequency of routine bioburden monitoring to production batch sizes, production batch frequencies, and statistical stability.
This revision addresses the lack of flexibility in the 3-month rule of the 2015 version. In supply chain production operations, raw material procurement cycles, batch processing schedules, transportation time to the radiation workshop, and microbiological laboratory culture cycles (sterility testing requires 14 days) can often lead to the audit execution date exceeding the 90-day limit. Under such circumstances, even if the manufacturer's baseline bioburden counts and microbial characteristics are fully under statistical control, cleanroom environmental monitoring data show no out-of-specification results, or a delay of a few days has no measurable negative impact on the sterility assurance of the released products, such delays could still result in non-conformities during regulatory inspections.
By expressing the requirement as a maximum 4-month interval while maintaining 4 audits per year, this standard strikes a balance between compliance and production realities, while retaining the necessary oversight to detect changes in bioburden or microbial radiation resistance.
Sources
- ylzbzz.org.cn › web (2026-10-15) - Original link: National Standard Interpretation: GB 18280.1—2025 "Sterilization of Health Care Products — Radiation — Part 1" - https://www.ylzbzz.org.cn/index.php?m=content&c=index&a=show&catid=31&id=305