Ethylene Oxide Vs. Vapor Phase Sterilization
What is sterilization, and why is it essential for sterile products?
Sterilization keeps patients safe from toxins and microbial illnesses when therapies or devices are consumed or used. Sterilization is any process that removes, kills, or deactivates all forms of life. 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. Commonly, sterile products undergo sterilization processes that utilize chemicals, heat, radiation, or filters. There are seven primary methods for medical device sterilization. These methods are steam sterilization, radiation sterilization, dry heat sterilization, sterilization by filtration, gas sterilization (such as ethylene oxide sterilization), vapor sterilization, and liquid sterilization. Chemical vapor sterilization (vapor phase sterilization) is a less common version of medical device sterilization. Most chemical vapor sterilization uses hydrogen peroxide vapor sterilization.
What is ethylene oxide sterilization?
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. EtO is used either as one hundred percent EtO, a carbon dioxide mixture, or a mixture with other gasses.
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 is vapor phase sterilization?
Vapor is an agent or molecule that is suspended in the air. Vapor phase sterilization sterilizes products through exposure to sporicidal agents suspended in the air. Most of the sporicidal agents are chemicals. Thus, vapor phase sterilization is also known as chemical vapor sterilization. Traditional chemical vapor sterilization agents are hydrogen peroxide (H2O2), peracetic acid (CH3CO3CH), formaldehyde (CH2O), and glutaraldehyde [CH2(CH2CHO)2]. Sterilizing gases and liquids differ from vapor phase agents, as vapor phase agents expose products to multiple phases (liquid, gas, etc.) during sterilization. The most common vapor sterilization method is hydrogen peroxide vapor sterilization.
How common is vapor phase sterilization?
Chemical vapor sterilization is much less common than ethylene oxide as it is harsher for more materials and less penetrative.
What products or medical devices can undergo ethylene oxide sterilization?
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 products or medical devices can undergo vapor sterilization?
Chemical vapor sterilization (like hydrogen peroxide vapor sterilization) works well for heat-sensitive materials and for the sterilization of surfaces.
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 items cannot be sterilized with vapor?
Items that are non-compatible with exposure to hydrogen peroxide or peracetic acid should not be vapor sterilized. Since vapor sterilization doesn’t penetrate as well as ethylene oxide, medical devices or items requiring certain inner surface penetration may not do well with vapor sterilization.
How is ethylene oxide sterilization performed?
Traditional EtO sterilization methods may use EtO-carbon dioxide mixtures with an 8.5% concentration of EtO or EtO-hydrochlorofluorocarbons mixture of 8.6-10% EtO. In some instances, high pressures of 29 pounds per square inch (psi) gauge are needed for sterilization protocols. Resting times for EtO sterilization range from 1-6 hours, and humidity ranges from 40-80%. With EtO sterilization, gas concentration can be increased to reduce EtO processing time.
How is vapor phase sterilization performed?
At room temperature, vapor phase agents (liquids or solids) vaporize and can be utilized for sterilization within a sealed chamber or vessel. Vapor sterilization must have a correct sterilant concentration, chamber temperature, and relative humidity for the items undergoing sterilization. Typically, the sterilant concentration (amount) will be determined from its injection quantities into the sterilization chamber. Vapor phase agents are most often introduced as an aqueous solution. For example, a standard vapor sterilization process involves adding items into the sterilization chamber and then adding heat and humidity. Next, the sterilant agent is introduced (sometimes through an atomizer), and the products are marinated in the vaporized sterilant for a set time. And finally, allowing the vapor to be removed from the system or evaporate before opening the chamber and removing the newly sterile items. If introduced as an aqueous solution, water moisture is introduced along with the sterilant. This added moisture is factored into humidity and condensation considerations for the sterilization process. Out of all vapor phase agents, hydrogen peroxide and peracetic acid are widely used and the most established for sterilization.
Hydrogen Peroxide Vapor Phase Sterilization
Hydrogen peroxide has a long history of being a liquid sterilant in healthcare and other industries. Hydrogen peroxide can be added into a sterilization chamber through multiple approaches. These approaches are continuous administration, intermittent administration, or injecting the entire dose of hydrogen peroxide all at once. Some vapor phase sterilization protocols have a drying step before adding the hydrogen peroxide. This drying step allows the hydrogen peroxide concentration within the sterilization chamber to increase without additional condensation. Hydrogen peroxide can also be introduced to a chamber as a liquid and exposed to targeted heating to create the vapor phase. Like gaseous sterilization methods, the sterilization chamber is aerated, and the sterilant gas is allowed to dissipate before the sterilized medical devices, products, and other items are removed.
Peracetic Acid Vapor Phase Sterilization
Peracetic acid may be used alone or mixed with hydrogen peroxide to sterilize medical products and devices. Peracetic acid is a liquid sterilant. An atomizer is used to distribute peracetic acid for vapor phase sterilization. The atomizer allows both liquid and vapor forms of peracetic acid to be present during sterilization. After peracetic acid exposure, evaporation is used to remove all peracetic acid from the system.
What are the advantages and disadvantages of vapor phase and ethylene oxide (EtO) sterilization?
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 residual limits to keep patients safe during medical device and product use. Current ISO 10993-7 EtO residual limits can be found here.
As mentioned earlier, ethylene oxide is not recommended for medical devices with embedded batteries due to the vacuum used during sterilization. Further, ethylene oxide should be avoided for materials sensitive to temperatures ranging from 30°C to 60°C or for medical devices made with materials that are sensitive to a humidity of less than 40%.
In contrast, vapor phase sterilization is often a faster method since the vapor’s liquid phase components kill microbes faster than the ethylene oxide gas alone. However, vapor phase sterilization can only be performed on products that can withstand exposure to vapor sterilants (hydrogen peroxide and peracetic acid) without deterioration. Further, ethylene oxide sterilization equipment is more prevalent in healthcare facilities than vapor sterilization systems.
Summary
Overall, medical devices, products, and therapies must be sterile. Sterilization is any process that removes, kills, or deactivates microbes. Ethylene oxide sterilization uses a combination of vacuum, humidity, temperature, and EtO gas to sterilize materials. In contrast, vapor sterilization inactivates microbes through exposure to sporicidal agents suspended in the air.
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).
Vapor sterilization works well for heat-sensitive materials that can tolerate exposure to vapor sterilants and for the sterilization of outer surfaces. Traditional EtO sterilization methods use EtO alone, EtO-carbon dioxide mixtures with an 8.5% concentration of EtO, or EtO hydrochlorofluorocarbons mixture of 8.6-10% EtO. Typical vapor phase sterilization agents are hydrogen peroxide, peracetic acid, formaldehyde, and glutaraldehyde. All in all, ensure you choose a contract testing organization that can provide appropriate sterility testing for your product needs.
Ethide Labs is a contract testing organization specializing in Sterilization Validations and Sterility Testing. Ethide Labs also offers Microbiology Testing, Bioburden Testing, EO Residual Testing, Bacterial Endotoxin 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.
Center for Disease Control. Ethylene Oxide “Gas” Sterilization: Guideline for Disinfection and Sterilization in Healthcare Facilities. Article. 2008.
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>).
United States Pharmacopeial Convention. <1229.11> Vapor Phase Sterilization. Rockville, MD, USA. 2021. (USPC <1229.11>).
