What medical devices can be sterilized with ethylene oxide?
How does the United States Food and Drug Administration (FDA) define sterile?
Under the strictest definition of sterility, an item or product is sterile when there is the complete absence of viable microorganisms (bacteria, yeasts, viruses, and molds). For regulatory purposes, sterility is defined by acceptance criteria based on calculated contamination probability. An acceptable level of contamination risk for most items is the probability of a single contaminated product out of a million manufactured products. However, sterility criteria may be more stringent or lax depending upon the intended use of the medical device or product.
What are ethylene oxide and sterilization by ethylene oxide?
Ethylene oxide (EO or ETO) is a gas commonly used to sterilize medical devices and products chemically. Ethylene oxide is a potent and highly penetrating alkylating agent. These characteristics make it an extremely effective sterilizing agent. However, at certain levels, ethylene oxide is also capable of causing cancer. Sterilization by ethylene oxide kills microorganisms through exposure to ethylene oxide gas under vacuum and humidity. EO is used either as one hundred percent EO or in combination with carbon dioxide.
How common is ethylene oxide sterilization?
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.
What items can be sterilized by ethylene oxide?
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.
What items cannot be sterilized with ethylene oxide, or are ethylene oxide resistant?
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).
What are the problems with sterilization by EO?
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 EO residual limits to keep patients safe during medical device and product use. Current ISO 10993-7 EO residual limits can be found here.
Summary
All in all, sterilization by ethylene oxide is alternative to traditional heat sterilization methods. Ethylene oxide sterilization uses a combination of vacuum, humidity, temperature, and gas to sterilize materials at lower temperatures than dry heat or steam sterilization methods. Most medical devices can be sterilized with ethylene oxide. However, medical devices with embedded batteries may not handle the vacuum of ethylene oxide sterilization cycles. Further, temperature-sensitive materials that are sensitive at 30°C to 60°C or humidity-sensitive materiasl should not be sterilized with ethylene oxide. Polymers like PP, HDPE, and LDPE can be sterilized with ethylene oxide. However, these polymers can be resistant to ethylene oxide sterilization at certain thicknesses. While effective, ethylene oxide can result in toxic residuals. Thus, any ethylene oxide sterilized medical devices or products must undergo ethylene oxide residual testing to meet FDA requirements.
Overall, ensure you choose a contract testing organization that can provide appropriate sterility and ethylene oxide residual testing for your unique medical device or product needs.
Ethide Labs is a contract testing organization specializing in EO Residual Testing. Ethide Labs also offers Bioburden Testing, Bacterial Endotoxin Testing, Microbiology Testing, Sterility Testing, Cytotoxicity 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.
Byron J. Lambert, Todd A. Mendelson & Michael D. Craven. Radiation and Ethylene Oxide Terminal Sterilization Experiences with Drug-Eluting Stent Products. AAPS PharmSciTech. Vol. 12: 1116–1126. 2011.
International Organization for Standardization. Biological evaluation of medical devices — Part 7: Ethylene oxide sterilization residuals. Geneva (Switzerland): ISO; 2008. (ISO 10993-7:2008).
Purell. Sterilization Of Polyolefins: A Methodological Overview. Lyondell Basell Industries.2011.
Michael J. Akers. Sterile Drug Products Formulation, Packaging, Manufacture, and Quality. Drugs and the Pharmaceutical Sciences. Informa Healthcare. 2010.
United States Food & Drug Administration. Ethylene Oxide Sterilization for Medical Devices. Digital Article. September 2020.
United States Pharmacopeial Convention. <1211> Sterility Assurance. Rockville, MD, USA. 2021. (USPC <1211>).
