To ensure they are safe for patient use, medical devices sterilized with ethylene oxide need to be adequately aerated to decrease residuals to acceptable limits. This primer covers the most important things you need to know about testing medical devices for ethylene oxide sterilization residuals under ISO 10993-7.
ISO 10993 covers the process of evaluating medical device biocompatibility to manage biological risk. To ensure that the medical device does not cause harmful reactions or complications during use, some medical devices must be sterilized. That sterilization process needs to be validated to ensure it effectively achieves the desired sterility assurance level (SAL). Part 7 of the ISO 10993 series covers ethylene oxide (EO) sterilization residual testing.
What Is ISO 10993-7?
The official title: ISO 10993-7:2008: “Biological evaluation of medical devices – Part 7: Ethylene oxide sterilization residuals.”
ISO 10993-7 specifies allowable limits for residual ethylene oxide (EO) and ethylene chlorohydrin (ECH) in medical devices sterilized with EO. It also outlines procedures for measuring EO and ECH and methods for determining compliance.
Why Is ISO 10993-7 & Ethylene Oxide Sterilization Residual Testing Important?
Ethylene oxide is a gas with robust sterilizing properties, effective against a wide range of harmful microorganisms. Because of this, EO sterilization is a widely used method for sterilizing medical devices.
However, EO gas is a hazardous substance that requires safety measures during and after the sterilization process. EO residuals can cause adverse reactions, so it’s important that medical devices sterilized with EO are properly degassed of EO residues before the devices are used. These residuals include:
- Ethylene oxide (EO)
- Ethylene chlorohydrin (ECH)
The standard requires you test for ethylene oxide sterilization residues for both single-use and reusable devices that use EO sterilization. This testing remains important during yearly medical device validation and whenever there’s a line extension, design change, process change, or manufacturing transfer.
What Is Ethylene Oxide Testing?
An important part of medical device product validation, EO testing is the process of testing a medical device for residual EO gas to validate sterilization. According to ISO 10993-7, there are two main types of residual EO analysis:
- Simulated-use extraction: simulates the exposure of patient to the specific part of the medical device that they would interact with during use.
- Exhaustive extraction: simulates the exposure of patient to the entire medical device.
To perform these extractions, there are two main methods:
1. EO Water Extraction
Water extraction involves extracting residual ethylene oxide from the medical device using water as a solvent. This is done to simulate conditions that the device might encounter during its actual use, such as contact with bodily fluids.
EO Water Analysis provides the quantitative data needed to assess the amount of residual EO on the medical device and ensure compliance with the ISO 10993-7 standard.
2. Headspace Extraction
Headspace Extraction involves extracting EO residuals by analyzing the headspace gas above the medical device, which can provide information about the amount of EO still present within or on the device.
EO Headspace Analysis detects and quantifies EO residuals in the headspace (gas phase) above a medical device.
Both methods – water and headspace extraction – are analyzed using gas chromatography techniques.
What Do Medical Device Manufacturers Need to Do to Follow ISO 10993-7?
Compliance with ISO 10993-7 is valuable for demonstrating the biological safety of your medical device with regard to EO sterilization and residual testing.
Here are the three most important things to know to follow ISO 10993-7:
1. Type of Patient
Different patient groups may have varying levels of sensitivity to residuals. Patients can be defined based on their age group and existing health conditions:
- Age group: pediatric, adult, or geriatric patients.
- Health conditions: patients with compromised immune systems, chronic illnesses, or other specific sensitivities. This can include special populations like pregnant women, as well.
It’s important to ensure the medical device is safe and effective for its intended user base.
2. Your Medical Device’s Exposure Category
ISO 10993-7 specifies standards depending on the level of exposure the patient has to the medical device.
- Limited exposure: single, multiple, or repeated contact up to 24 hours
- Prolonged exposure: 24 hours – 30 days
- Permanent contact: 30+ days
Knowing your exposure category helps determine the appropriate testing requirements as well as the acceptance limits for your medical device.
3. Exposure Limits
Depending on your exposure category, your medical device must not exceed the allowable limits for EO and ECH.
- Limited exposure limit: 4 mg in the first 24 hours.
- Prolonged exposure limit: average 2 mg per day, and no more than 4 mg in the first 24 hours and 60 mg in the first 30 days.
- Permanent contact: average 0.1 mg per day, and no more than 4 mg in the first 24 hours, 60 mg in the first 30 days, and 2.5 g in a lifetime.
Conclusion
Ethylene oxide sterilization validation testing is a critical part of a complete medical device biological evaluation for products sterilized using EO. Knowing your exposure limits and your medical device’s exposure category will help you plan your testing program and meet the requirements of ISO standards.
NAMSA’s technical and regulatory experts leverage their scientific knowledge of microbiology for product and manufacturing environment validations. We can help you validate cleaning, disinfecting, and sterilization processes of single-use, reusable, and third-party reprocessed devices. Our study design for complete EO validation is for your specific product and process, and all aspects of the studies follow the requirements of ISO. Speak with an expert about your upcoming project to see how we can help you.
