ISO 17664:2017[1] as well as FDA[2] state that if a medical device is intended to be sterilized, at least one validated sterilization method must be specified in the IFU. Consequently, if devices are intended to be steam sterilized, at least one validated steam sterilization cycle must be identified in the IFU depending on the critical cycle parameters (sterilization method and type, exposure time and temperature as well as dry time). Additionally, the sterilization methods and parameters must be technically feasible to the user. Healthcare facilities around the world will adhere to slightly different cycle parameters for the steam sterilization of reusable medical devices, leading to the inclusion of different steam sterilization cycles in device manufacturer’s IFUs. Theoretically, all cycle parameters included in the IFU should be validated. However, in certain situations a worst-case approach can be used to cover multiple cycle parameters in fewer validations.
Examples of cycle parameters
The following exposure temperatures and times are often used for steam sterilization of reusable medical devices:
- Pre-vacuum at 132°C for 4 minutes, this is the cycle used in US hospitals.
- Pre-vacuum at 134°C for 3 minutes up to 18 minutes. The most common temperature used for steam sterilization in EU hospitals, although higher temperatures (up to 138°C) are used as well. Exposure times vary between 3 and 18 minutes depending on the country.
- Pre-vacuum at 121°C for 15 minutes. This cycle is less common, but sometimes used for dental instruments.
- Gravity displacement at 121°C for 30 minutes. Gravity displacement is phasing out, but is still being used for dental instruments in smaller dental facilities that do not have access to pre-vacuum steam sterilizers.
Steam sterilization validations consist of assessing the sterility assurance level, validating the dry time, and temperature profiling. Certain aspects of the validation need to be performed for each set of cycle parameters specified in the IFU, whereas a worst-case approach may be used for others as outlined below.
Assessing the sterility assurance level
Reusable medical devices must be validated to ensure a sterility assurance level (SAL) of ≤ 10-6 is achieved, which means there is a maximum probability of one in a million devices being non-sterile after exposure to a sterilization process. This validation is performed using biological indicators (BIs) of appropriate test organisms posing an appropriate challenge to the steam sterilization process. The validation must show the steam sterilization process is capable of inactivating these BIs. Although this assessment can be performed for each set of cycle parameters, this aspect of the steam sterilization validation is particularly amenable to a worst-case approach. Once the inactivation of BIs has been evaluated, a justification can be made for testing a worst-case hybrid cycle; combining the worst-case temperature and worst-case exposure time into one worst-case cycle for validation. EU and US pre-vacuum steam sterilization cycles are sometimes validated using a worst-case hybrid cycle of 132°C for 3 minutes. If inactivation of appropriate BIs can be shown for this cycle, it is reasonable to assume that a longer cycle at the same temperature (132°C for 4 minutes), a cycle that is equally long but runs at a higher temperature (134°C for 3 minutes), or a longer cycle at a higher temperature (e.g. 134°C for 18 minutes) will also be capable of inactivating these BIs. Notified bodies commonly accept this approach. Similarly, for devices only intended to be marketed in the EU, if BI activation can be shown for a pre-vacuum steam sterilization cycle at 134°C for 3 minutes, longer cycles at the same temperature can be considered validated as well.
For cycles with a temperature of 121°C, performing a worst-case hybrid cycle is not possible; these cycles are always validated by themselves. The reason for this is the difference in exposure time and temperature. It is simply too large with the cycles performed at 132°C or 134°C to define a reasonable worst-case hybrid cycle. Gravity displacement cycles are less effective than pre-vacuum steam sterilization cycles. They are validated separately as well.
Dry time validation
In addition to exposure time and steam temperature, sterilization cycles include a drying time which is commonly at least 20 minutes, which must be validated to ensure devices are dry following steam sterilization. There is no known correlation between drying performance and cycle length, which is why a worst-case approach is generally not possible and dry time validations must be performed for all cycle parameter sets. Consequently, whereas the SAL can be assessed simultaneously for EU and US pre-vacuum steam sterilization cycles using a worst-case hybrid cycle, drying times should be validated separately for each set of parameters.
One exception where a worst-case approach can be used is the validation of multiple EU pre-vacuum steam sterilization exposure times. As mentioned previously, EU steam sterilization cycles are commonly performed at 134°C, but exposure times can range from 3 to 18 minutes with 3, 4, 5, 10, or 18 minute parameters all being possible depending on the country. Rather than validating drying times for all possible cycles, the shortest (3 minutes) and longest cycles (18 minutes) can be selected to perform drying time verification. If both cycles are tested and validated, all drying time cycles in between are considered validated as well. Similarly, if the intended parameters differ in exposure temperature, e.g., 134°C – 137°C for 3 minutes, both 134°C for 3 minutes and 137°C for 3 minutes would be validated drying times.
Temperature profiling
US FDA places less emphasis on temperature data, although rejections based on the absence of temperature data do occur and have recently become more frequent. However, temperature profiling according to ISO/TS 17665-2:2009 Annex A is considered a necessity in the EU. Therefore, we always advise our sponsors to test both US and EU steam sterilization cycles for temperature profiling. A worst-case approach may be used validating only the shortest EU cycle rather than all EU pre-vacuum steam sterilization cycles at 134°C. If a product can obtain the exposure temperature set point and hold it for the required time in a 3-minute exposure cycle, it should be able to do the same during an 18-minute exposure cycle.
In conclusion
It is important to realize that all steam sterilization cycles in the IFU must be validated, but worst-case approaches can be used to perform fewer validations while still covering all steam sterilization cycles. If you are unsure about whether your notified body or the FDA will accept this, it is best to check with them beforehand.
[1] ISO 17664:2017 Processing of health care products – Information to be provided by the medical device manufacturer for the processing of medical devices.
[2] FDA 2015 Reprocessing medical devices in health care settings: Validation methods and labeling – Guidance for industry and food and drug administration staff
