Most manufacturers start with the impression that radiation sterilization means irradiating at the conventional dose and calling it done. The impression is not entirely wrong, since one dose level really is the one most widely used, but you cannot apply it straight out of the box. You first have to demonstrate, using a method the standard prescribes, that the dose is adequate for your product, and once demonstrated it has to be re-confirmed on a schedule. Those two activities are dose establishment and dose audit, and both live in ISO 11137-2.
Skipping this step has a direct consequence. Reviewers ask for it during registration or submission, and dose establishment is not something you can produce in a few days: it requires sampling across production batches, bioburden determination, irradiation at a verification dose, and sterility testing.
How the ISO 11137 family divides the work
Radiation sterilization is not one standard but a series. The three parts manufacturers deal with most are:
| Part | Scope | Current edition |
|---|---|---|
| ISO 11137-1 | Overall requirements for development, validation and routine control of the sterilization process | 2025 |
| ISO 11137-2 | Methods for establishing the sterilization dose | 2013 |
| ISO 11137-3 | Guidance on dosimetric aspects, covering dose measurement and the use of dosimeters | 2017 |
The Chinese national counterparts are the GB 18280 series, and they are mandatory standards: GB 18280.1-2015 and GB 18280.2-2015 both took effect on 2017-07-01. Note that a 2025 edition of GB 18280.1 has been issued, with an implementation date of 2029-01-01, which means the next few years are a transition period in which the old and new editions coexist. If your product is on a dual track for export and domestic registration, decide during protocol design which edition you are working to and how the report will state it.
Dose establishment starts with how dirty the product is
Every dose-setting method starts from bioburden, the microbial population carried by the product before sterilization. The logic is plain: the cleaner the product, the lower the dose it needs, and if you do not know the microbial background you have no basis for claiming that any given dose is sufficient.
Bioburden is determined in accordance with ISO 11737-1, sampling across the number of production batches the method requires. The quality of this data determines everything downstream. If the production environment fluctuates and batch-to-batch bioburden varies noticeably, every subsequent method choice is affected.
Choosing between the method families
ISO 11137-2 offers two lines of thinking. In practice these are the routes that come up most:
| Method | Approach | Main precondition | Sample consumption | Typical fit |
|---|---|---|---|---|
| VDmax25 | Verifies that the conventional dose the method is named for is adequate for this product | Average bioburden at or below the ceiling the method allows | Comparatively low | Routine products with controlled bioburden, willing to use the conventional dose |
| VDmax15 | Verifies adequacy at a lower dose level | Tighter bioburden requirement | Comparatively low | Dose-sensitive products aiming to reduce the delivered dose |
| Method 1 | Derives the required sterilization dose from bioburden data | Presupposes no target dose | Noticeably higher | High or variable bioburden, or products the conventional dose does not suit |
The selection logic runs roughly like this.
If you intend to use the conventional dose and bioburden is low, VDmax25 is the lowest-cost route. It is a verification exercise: assume the dose is adequate, then irradiate at a lower verification dose to test whether the assumption holds. Sample consumption is comparatively low and the timeline is short.
If the product is dose-sensitive, for instance polymers that embrittle or discolor at higher doses, or a drug-device combination whose active constituent is affected, a lower-dose route such as VDmax15 is worth considering. The bioburden requirement tightens accordingly, so manufacturing has to help bring the background down.
If bioburden is high or unstable, the preconditions for the VDmax family do not hold and you move to Method 1, deriving the dose from data. The price is noticeably higher sample consumption and a longer timeline.
The number of batches to sample, the way verification doses are determined and the acceptance rules for each method are governed by the text of the standard in its currently effective version, and no figures are reproduced here.
Dose audit: establishment is not the finish line
This is the step most often overlooked. Dose establishment demonstrates that the dose holds at the bioburden level prevailing at that time. Bioburden moves with raw materials, production environment, season and process adjustments, so it has to be re-confirmed periodically.
A dose audit has two components: re-determining bioburden, and irradiating samples at a verification dose and running sterility tests. The first shows whether the background has drifted; the second tests the validity of the dose directly.
When an audit fails, you do not simply repeat it. Investigate the cause first, asking whether the background has genuinely risen or whether something went wrong in sampling or testing, and then decide whether to raise the sterilization dose or to bring bioburden back down on the production side. The cost difference between those two paths is large: raising the dose means re-evaluating material compatibility and may affect the shelf life of the product.
Separately, when the design, materials, supplier, packaging format, manufacturing site or loading pattern changes, assess whether dose establishment has to be repeated even if the audit interval has not elapsed.
How this connects with other work
Radiation sterilization validation is not a standalone project. It is directly coupled to several other activities:
- Material compatibility and shelf life. Irradiation changes polymer performance, so post-sterilization performance verification and accelerated aging have to be run on product irradiated at the validated dose.
- Package integrity. The sterile barrier system has to survive sterilization and distribution intact; see packaging validation.
- Biological evaluation. Irradiation can change how a material releases chemicals, so samples for chemical characterization and biological testing should be sterilized product; see biocompatibility testing.
- Suitability of the sterility test method. The sterility test method used in dose audits has itself to be confirmed suitable for the product.
On sequencing, get bioburden and dose establishment out of the way first, then schedule material performance and aging work, because the samples for the latter have to have been irradiated at the finally validated dose. Reversing the order produces rework.
Three common misconceptions
One: the conventional dose is mandated by regulation. It is not. It is a value the industry has used for a long time, and no standard requires it. It is common because, for most products with modest bioburden, substantiating it through VDmax25 is comparatively inexpensive. For a different product, whether it holds is a question for data.
Two: dose establishment is a one-off exercise. The validity of a dose is tied to the bioburden level at the time it was established. Once the production environment, raw material supplier or packaging format changes, the earlier conclusion may no longer hold, which is exactly why periodic dose audits exist.
Three: a passing sterility test means sterilization validation is complete. The sterility test is one element inside a dose audit. Sterilization validation also covers installation qualification, operational qualification, performance qualification and dose mapping, as required by ISO 11137-1 and GB 18280.1. A sterility test report on its own is usually not enough at submission.
Dose distribution is also strongly tied to the loading pattern. For the same product, change the way cartons are stacked and the minimum and maximum dose locations inside the carton can move with it. The loading pattern used in validation therefore has to match routine production, and a change to production loading calls for re-evaluation.
Samples and documentation
Protocol design usually calls for:
- Product structure and material list, covering every component relevant to sterilization
- Manufacturing process and environmental controls, used to judge how stable bioburden is likely to be
- Packaging format and loading pattern, since dose distribution is tightly coupled to loading
- Target dose and any historical data, since previous irradiation history and past bioburden results are valuable inputs
- The batch definition for the product, since sampling has to span different production batches
Sample quantity depends on the method chosen and the number of product variants, and a definitive list is issued once the protocol is agreed. For products with high bioburden, run a few exploratory batches before fixing the method rather than going straight to VDmax25 and reworking when the precondition turns out not to hold. For related services see sterilization validation, and comparable projects are described under case studies.
Working with SUNGO Lab
SUNGO Lab (Shanghai Shage Medical Technology Co., Ltd.) is accredited by CNAS, CMA and IAS (USA), with laboratories in Shanghai and Hefei. We take on testing associated with sterilization validation and can issue reports in the formats expected for domestic registration and for export submissions. Alongside irradiation we cover ethylene oxide and moist heat routes, together with supporting work on packaging, shelf life and biocompatibility. The full scope is listed under testing services. Accreditation marks demonstrate technical competence within the accredited scope; they are not a commitment regarding market access.
If you are unsure which dose-setting method suits your product, how many samples to reserve, or how to schedule audit intervals, send us the product structure and a description of your manufacturing situation and we will confirm a protocol first. Call +86 132 4819 8029 or request a quote.