How To Prepare Your Samples For Ethylene Oxide Residuals Testing
What are ethylene oxide (EtO) gas and EtO sterilization?
Ethylene oxide (also called EO or EtO) is a chemical gas commonly used to sterilize medical devices and products. Ethylene oxide is a potent and highly penetrating alkylating agent. These characteristics make it an extremely effective sterilizing agent under vacuum and humidity. In fact, approximately 20 billion medical devices are sterilized with ethylene oxide each year. Thus, ethylene oxide sterilization accounts for about half of sterilized medical supplies in the United States. However, at certain levels, ethylene oxide is also capable of causing cancer.
What is ethylene oxide (EtO) residuals testing?
The primary issue with using ethylene oxide for sterilization is its absorption into certain materials and its reaction with water (or other material components) to form toxic residual compounds (ethylene oxide, ethylene glycol, and ethylene chlorohydrin).
These residual compounds are hazardous both to people and to the environment. Ethylene glycol is formed from ethylene oxide and water reaction, while ethylene chlorohydrin is formed from the interaction of ethylene oxide and chloride compounds. Products sterilized with ethylene oxide must meet strict EtO residuals limits to keep patients safe during medical device and product use. EtO residuals testing assesses medical devices and other EtO sterilized products or packaging for their residual ethylene oxide and ethylene chlorohydrin content.
What products require ethylene oxide (EtO) residuals testing?
Any items sterilized using ethylene oxide that come in physical contact with a patient require EtO residuals testing. If your device or product isn’t in physical contact with the patient, there is no need to perform EO residual testing. Due to its low-temperature conditions, ethylene oxide sterilization is well suited for medical devices with embedded electronics and medical devices that cannot withstand steam (autoclave) sterilization. Ethylene oxide is also used to sterilize the personal protective equipment and drapes used by doctors and healthcare workers. Medical device types that are sterilized with ethylene oxide range from external wound dressings to implantable stents. Other devices include heart valves, vessel closure devices, catheters, and guidewires. Products combining devices, drugs, and biologics within a single item may also be sterilized using ethylene oxide. Ethylene oxide can sterilize almost every type of plastic. Standard materials sterilized with ethylene oxide are plastics, heat-labile materials (e.g., electronics), elastomer polymeric materials, and biomaterials.
Ethylene oxide is not recommended for medical devices with embedded batteries due to the vacuum used during sterilization. Ethylene oxide sterilization is not recommended for materials sensitive to temperatures ranging from 30°C to 60°C or for medical devices made with materials that are sensitive to humidity. Polymers that are resistant to ethylene oxide sterilization are polyolefin resins such as polypropylene (PP), high-density polyethylene (HDPE), and low-density polyethylene (LDPE).
Overall, before preparing samples for EtO residuals testing, determine if your product requires ethylene oxide residuals testing. If your device does require ethylene oxide residuals testing, determine which ethylene oxide extraction method is best for your device, find out what your EtO and ECH residuals limits are, and learn how to calculate your ethylene oxide residuals. If you need ways to reduce your ethylene oxide residuals to meet the required limits, please visit our article on key factors that influence EO residuals levels.
How to prepare samples for testing for ethylene oxide (EtO) residuals
Samples used for residual testing must be representative of the marketed product. The items below are factors to consider when selecting appropriate product samples for ethylene oxide residuals testing.
#1: Product material composition
Materials absorb, retain, and release ethylene oxide at different rates. If chloride ions are available in product materials, free EtO can be converted to ethylene chlorohydrin (ECH) and create a different EtO residue profile. Medical devices made of two different materials may need EtO residuals analysis for each material for accurate analysis. Material size, thickness, coatings, and processing all play a role in EtO retention, as well.
#2: Product packaging
The degree to which ethylene oxide gas penetrates and dissipates into product packaging materials depends upon the product packaging selected for use. For example, some packaging materials are dense and difficult to penetrate. Other materials are easier to penetrate and may be made with available chloride ions for ECH residue formation.
#3: Ethylene oxide sterilization cycle parameters
The EtO sterilization process parameters hugely affect EtO residue levels. The ethylene oxide concentration alone (100% EtO versus 30% EtO) drastically impacts the available EtO on products after sterilization. Other ethylene oxide sterilization parameters that impact ethylene oxide residual levels include the EtO exposure time, the EtO exposure temperature, the sterilization cycle humidity level, the product’s orientation during sterilization, and the load density for the EtO sterilization cycle. Longer exposure times, higher temperatures, denser sterilization cycle loads all lead to the risk of greater EtO residual accumulation after sterilization. If looking for alternatives to EtO sterilization, consider radiation sterilization or visit our sterilization comparison chart.
#4: Ethylene oxide sterilization aeration
EtO sterilization cycles have aeration periods to allow toxic EtO gas to dissipate. Residual ethylene oxide in devices varies due to multiple variables during aeration. Some aeration variables that impact EtO residual levels include the aeration temperature, humidity, product load density, product orientation, available airflow, the available product surface area during aeration, and aeration time. Some products double their aeration rate for each 10 C increase in aeration temperature. Aeration humidity, temperature, and airflow greatly impact ECH formation. Aeration rates may fluctuate with the seasons if ambient warehouse conditions are used versus controlled laboratory conditions. Any seasonal fluctuations should be noted during EtO residuals assessment. In some instances, samples may need to be held in conditions that approximate the lowest temperature they will be stored during aeration to simulate a worst-case scenario.
#5: Sample retrieval
Ethylene oxide residual levels are greatest immediately following EtO sterilization. Product samples are often shipped to a contract testing site far from the sterilization site for EtO residual assessment. In these situations, steps must be taken to prove that the shipped samples have substantially similar EtO levels compared to the rest of the sterilized product load.
#6: Grouping devices for quality assurance testing
Medical devices and implants may be grouped into a family of “like devices” for EtO residuals testing if the material composition, packaging, manufacturing processes, sterilization processes, and use are substantially similar. For “like devices,” the “worst-case” product within a family is assessed as a representative of the entire family of devices. However, for family representatives to be assessed, the variables mentioned above (e.g., sample retrieval, aeration, EtO sterilization cycle parameters, etc.) must be well controlled between devices within a family.
How to prepare samples for shipment
EtO residual testing samples should remain with their original product load until the desired aeration is reached. If test samples are being prepared for shipment, packages should be retrieved and immediately frozen with dry ice. Shipment time for EtO testing should be minimized, and samples should be stored frozen if the shipment is delayed. Test samples may also be taken from the product load at the desired aeration interval and placed into a sealed headspace vial for shipment to the contract testing facility.
In addition to ethylene oxide sterilized samples, a set of samples that have not undergone ethylene-oxide sterilization may be needed for testing. These samples are considered “blanks” and are assessed for any ethylene oxide or ethylene oxide residuals before ethylene oxide sterilization has taken place.
Summary
Overall, ethylene oxide (also called EO or EtO) is a chemical gas commonly used to sterilize medical devices and products. In fact, approximately 20 billion medical devices are sterilized with ethylene oxide each year. However, ethylene oxide residues are cancer-causing and can be left on products after sterilization. Ethylene oxide (EtO) residuals testing evaluates the quantity of EtO left on products following EtO sterilization and ensures that medical devices are safe for patient use. If you know that your product will require testing for ethylene oxide residues, the following six factors should be considered when selecting appropriate product samples for ethylene oxide residuals testing. These six factors are product composition, packaging, ethylene oxide sterilization cycle parameters, ethylene oxide sterilization aeration, product sample retrieval, and grouping devices for quality assurance testing. When shipping your samples, ship sterilized products with dry ice to prevent unwanted EtO aeration during sample shipment to your testing facility. All in all, ensure you choose a contract testing organization that can support you with appropriate EtO residuals testing for your unique medical device and product needs.
Ethide Labs is a contract testing organization specializing in Ethylene Oxide Residual Testing. Ethide Labs also offers Microbiology Testing, Bioburden Testing, Cytotoxicity Testing, Bacterial Endotoxin Testing, Sterility Testing, Environmental Monitoring & Package Integrity Testing services for medical device companies and allied industries. Ethide is an ISO 13485 certified facility.
References
Bernhard Linke. Sterilization methods and impact on electronics in medical devices. EE Times. July 2011.
International Organization for Standardization. Biological evaluation of medical devices — Part 7: Ethylene oxide sterilization residuals. Geneva (Switzerland): ISO; 2008. (ISO 10993-7:2008).
Michael J. Akers. Sterile Drug Products Formulation, Packaging, Manufacture, and Quality. Drugs and the Pharmaceutical Sciences. Informa Healthcare. 2010.
Purell. Sterilization Of Polyolefins: A Methodological Overview. Lyondell Basell Industries.2011.
United States Food & Drug Administration. Ethylene Oxide Sterilization for Medical Devices. Digital Article. September 2020.
