Based on a gas diffusion process, Ethylene Oxide EO or ETO is capable of sterilizing and rendering products free of viable microorganisms. The process requires the simultaneous control of four variables, but interdependent parameters: gas concentration, temperature, relative humidity, and time of exposure.
EO sterilization effectiveness depends on its ability to freely diffuse through a product and packaging. All products must be placed in breathable packaging that allows gas to penetrate the sterile barrier and reach all surfaces of the device or product.
EO is considered the sterilization method with the broadest application available for medical products and medical devices due to its effectiveness at lower temperatures and its general compatibility with a diversity of materials, resins, and product types, including:.
Generic filters. Have a question? Ethylene Oxide Sterilization. Best Suited For EO is considered the sterilization method with the broadest application available for medical products and medical devices due to its effectiveness at lower temperatures and its general compatibility with a diversity of materials, resins, and product types, including: Polymer resin-based products Single-use medical devices Procedure kits Surgical trays Synthetic gowns External terminal sterilization of sealed combination drug-devices filled syringes, drug-coated stents.
The FDA believes the Ethylene Oxide Sterilization Master File Pilot Program should result in sterilization facilities using a greatly reduced amount of ethylene oxide while still providing robust patient safeguards. The FDA will continue in its efforts to reduce over-reliance on ethylene oxide for medical device sterilization and will provide updates on future Master File acceptances.
Medical devices are sterilized in a variety of ways including using moist heat steamdry heat, radiation, ethylene oxide gas, vaporized hydrogen peroxide, and other sterilization methods for example, chlorine dioxide gas, vaporized peracetic acid, and nitrogen dioxide.
Ethylene oxide sterilization is an important sterilization method that manufacturers widely use to keep medical devices safe. For many medical devices, sterilization with ethylene oxide may be the only method that effectively sterilizes and does not damage the device during the sterilization process. Medical devices made from certain polymers plastic or resinmetals, or glass, or that have multiple layers of packaging or hard-to-reach places for example, catheters are likely to be sterilized with ethylene oxide.
Literature shows that about fifty percent 123 of all sterile medical devices in the U. The types of devices that are sterilized with ethylene oxide range from devices used in general health care practices for example, wound dressings to more specialized devices used to treat specific areas of the body for example, stents.
An important element of our regulatory framework is a robust standards program. The FDA encourages medical device sponsors to use FDA-recognized voluntary consensus standards in their submissions, as conformity to relevant standards streamlines regulatory review and fosters quality. These standards help ensure levels of ethylene oxide on medical devices are within safe limits since long-term and occupational exposure to ethylene oxide has been linked to cancer.
Learn more about the risks of ethylene oxide on the National Institutes of Health web page on ethylene oxide. If a medical device manufacturer changes the method, process, or the facility identified in its original PMA submission for sterilizing its devices, the manufacturer generally needs to submit a PMA supplement so that the agency can review these changes and determine if they also meet internationally agreed-upon voluntary standards that the FDA recognizes.
For manufacturers that are k holders, sterilization method, process or site modifications can be assessed with the FDA guidance document: " Deciding When to Submit a k for a Change to an Existing Device " for determination on whether the sterilization modifications would trigger the need for resubmission.
The FDA also inspects industrial facilities that sterilize medical devices and medical device manufacturing facilities to make sure that they have validated sterilization processes that meet FDA-recognized standards. State health departments inspect health care facilities that use ethylene oxide to sterilize medical devices. Learn more about guidelines for sterilization in health care facilities on the Centers for Disease Control and Prevention web page.
The US Environmental Protection Agency EPA reviews and enforces the Clean Air Act regulations for sterilization facilities that emit ethylene oxide to ensure that they protect the public from significant risk. The FDA is actively working with sterilization experts, medical device manufacturers, and other government agencies to advance innovative ways to sterilize medical devices with lower levels of currently used agents, and employ new agents or alternatives, while maintaining device safety and effectiveness.
On July 15,the FDA announced two public innovation challenges to encourage development of novel sterilization methods, which could include new devices or new modalities that are safe and effective for sterilizing medical devices:. Refer to each challenge page for details on the selected participants and next steps.
Meeting materials are available on the Advisory Committee Meeting Announcement page. One recommendation from the advisory committee meeting is for device manufacturers to begin, as soon as possible, reducing the amount of paper such as the labeling and instructions for use manuals that is included in the sterile device package.
An ethylene oxide sterilized medical device must be sealed in a carefully designed gas-permeable package that enables the ethylene oxide gas to enter. When the sterilization load encompassing all the materials inserted into the sterilizer chamber with the device includes a large amount of paper with the device, it hinders the ethylene oxide getting to the device and generally means that more ethylene oxide is required.An Ethylene Oxide EO Sterilization Validation is designed to assist the manufacturer in the development of a sterilization process that delivers the appropriate sterility assurance level and ensures repeatability for each product type developed.
All types of products, whether sterilized in-house or by a contract sterilizer, must be validated to ensure compliance with national and international standards.
Nelson Labs specializes in ethylene oxide sterilization validations, and we can partner with you as well as many contract sterilization facilities through the entire process from protocol generation to final report completion. See below for more details. Our sterilization specialists will guide you through prevalidation testing and cycle development, as well as the validation process, routine monitoring and revalidation requirements.
Generic filters. Sterilization Validation — Ethylene Oxide EO Ethylene Oxide Sterilization Validations An Ethylene Oxide EO Sterilization Validation is designed to assist the manufacturer in the development of a sterilization process that delivers the appropriate sterility assurance level and ensures repeatability for each product type developed.
An Ethylene Oxide EO Sterilization Validation is designed to assist the manufacturer in the development of a sterilization process that delivers the appropriate sterility assurance level and ensures repeatability for each product type developed. All types of products, whether sterilized in-house or by a contract sterilizer, must be validated to ensure compliance with national and international standards.
Nelson Labs specializes in Ethylene Oxide Sterilization Validations, and we can partner with you as well as many contract sterilization facilities through the entire process from protocol generation to final report completion.
See below for more details. Nelson Labs offers complete package testing and services in compliance with global regulatory requirements. A radiation sterilization validation determines the appropriate radiation sterilization dose for a product that requires a sterile label claim. For ongoing process monitoring, Nelson Labs offers quarterly dose audit QDA coordination services that include dosing, testing, consulting and summary reports.
If a sterile label claim is required and the sterilization method will be radiation, a validation is required to determine the appropriate sterilization dose. Nelson Labs has vast experience providing validations for complex or unique products, or products which cannot handle large doses of radiation. The testing establishes the pertinent sterilization parameters for health care reprocessing instructions.
Based on the data obtained through testing, the manufacturer will be able to provide health care facilities with validated sterilization parameters. For reusable instruments, liquid chemical or thermal disinfection may be acceptable alternatives. In addition, manufacturers should validate end of life cycles for reusable or reprocessed medical devices to demonstrate functionality with repeated exposures and clinical simulations.
Nelson Labs can assist in study design and execution of functionality and repeated use studies. Clinical batch release studies can be performed on a limited basis for novel devices and products that require sterilization prior to receiving marketing approval. Nelson Labs has the equipment and qualified personnel to help guide you through the process.
Our experts will provide individualized consultation and are here to help simplify the complex regulatory and standard recommendations. Process monitoring is an essential part of any sterilization validation and routine cycle verification. We also offer product inoculation services to verify worst-case cycle efficacy.
This test allows manufacturers to determine membrane pore sizes and is an excellent lot release test in compliance with both the ASTM F and HIMA guidance documents. Generic filters. Sterilization Validations. Ethylene Oxide Sterilization Validation An Ethylene Oxide EO Sterilization Validation is designed to assist the manufacturer in the development of a sterilization process that delivers the appropriate sterility assurance level and ensures repeatability for each product type developed.
Radiation Sterilization Validation Nelson Labs offers complete package testing and services in compliance with global regulatory requirements.Updated: Dec 13, Lena Shahbandar, MD.Ethylene Oxide Sterilization, Revision of Annex E, Single Batch Release
History of Ethylene Oxide:. Ethylene oxide has been in commercial use for approximately 90 years. It was initially used in the agricultural context to prevent Japanese beetle dispersion1.
In the medical field, ethylene oxide has been used for decades as an established means to effectively sterilize heat sensitive materials. However, ethylene oxide is a highly flammable compound with carcinogenic and mutagenic properties. The industry standard of using CFCs was then further altered in with the passing of the Montreal Protocol, which was signed and ratified by all UN member nations, in the effort to reduce the depletion of the ozone layer.
After the passage of the Montreal Protocol, sterilization with ethylene oxide was shifted to pure ethylene oxide1. Concurrent with the increased awareness of the toxicity of EtO as well as the restriction of use of CFCs, the industry has seen an emergence of alternative technologies that improve sterilization time and reduce toxicity.
Alternative sterilization options:. However, the last two decades have seen an emergence of alternative sterilization options. The following chart describes advantages and disadvantages of the sterilization methods1,7,8,9, Rutala William and David Weber. August 31, Harrell R et al. While ethylene oxide is effective in the sterilization of plastics, and the benefits of using a single sterilant with high product compatibility makes a strong argument for the continued use of EtO, the following chart also demonstrates there are alternative sterilization methods available for almost every plastic without the added risk of ethylene oxide Medical Sterilization:.
Medical device and product sterilization is essential to maintain the safety and health of patients undergoing medical interventions. There are two main categories for medical sterilization—the sterilization of reusable materials and the sterilization of disposables.
Hospitals primarily sterilize reusable materials. Over the past decade, many hospitals have successfully moved away from use of ethylene oxide due to its cost, inefficiency, and toxicity. Some documented transitions in hospital settings are noted below:. This hospital implemented use of both peracetic acid and hydrogen peroxide plasma devices and was able to significantly reduce its ethylene oxide use Joseph Hospital and Medical Center in Phoenix demonstrated even further success in reduction of ethylene oxide sterilization usage.
In many Chicago-area hospital systems, there has been a large shift away from ethylene oxide, consistent with the above-mentioned efforts. Advocate Good Samaritan and the entire Advocate system shifted away from ethylene oxide approximately a decade ago. Saint Anthony Hospital eliminated use inand Swedish Covenant Hospital terminated use in On the other hand, in the arena of disposable sterilization, ethylene oxide remains a major player.
The sterilization of disposable medical materials occurs largely at manufacturers or off- site, contract sterilization companies.ETO is a colorless gas that is flammable and explosive.
These influence the effectiveness of ETO sterilization.
U.S. Food and Drug Administration
The use of ETO evolved when few alternatives existed for sterilizing heat- and moisture-sensitive medical devices; however, favorable properties Table 6 account for its continued widespread use. This mixture is less expensive than ETO-hydrochlorofluorocarbons HCFCbut a disadvantage is the need for pressure vessels rated for steam sterilization, because higher pressures psi gauge are required.
The main disadvantages associated with ETO are the lengthy cycle time, the cost, and its potential hazards to patients and staff; the main advantage is that it can sterilize heat- or moisture-sensitive medical equipment without deleterious effects on the material used in the medical devices Table 6. Acute exposure to ETO may result in irritation e. ETO should be considered a known human carcinogen. The basic ETO sterilization cycle consists of five stages i. Most modern ETO sterilizers combine sterilization and aeration in the same chamber as a continuous process.
There are no federal regulations for ETO sterilizer emission; however, many states have promulgated emission-control regulations. ETO is absorbed by many materials. For this reason, following sterilization the item must undergo aeration to remove residual ETO. Guidelines have been promulgated regarding allowable ETO limits for devices that depend on how the device is used, how often, and how long in order to pose a minimal risk to patients in normal product use.
Sterilization Validation – Ethylene Oxide (EO)
ETO toxicity has been established in a variety of animals. Exposure to ETO can cause eye pain, sore throat, difficulty breathing and blurred vision. Exposure can also cause dizziness, nausea, headache, convulsions, blisters and vomiting and coughing. ETO has been linked to spontaneous abortion, genetic damage, nerve damage, peripheral paralysis, muscle weakness, and impaired thinking and memory. Alkylation, or the replacement of a hydrogen atom with an alkyl group, within cells prevents normal cellular metabolism and replication.
Like all sterilization processes, the effectiveness of ETO sterilization can be altered by lumen length, lumen diameter, inorganic salts, and organic materials.
ETO is used in healthcare facilities to sterilize critical items and sometimes semicritical items that are moisture or heat sensitive and cannot be sterilized by steam sterilization. Skip directly to site content Skip directly to page options Skip directly to A-Z link. Infection Control.Ethylene Oxide EtO sterilization is mainly used to sterilize medical and pharmaceutical products that cannot support conventional high temperature steam sterilization — such as devices that incorporate electronic components, plastic packaging or plastic containers.
EtO gas infiltrates packages as well as products themselves to kill micro organisms that are left during production or packaging processes. Pure EtO gas boiling point is Most of the time, it is mixed with Nitrogen or CO2.
This explosive condition requires Intrinsic Safe material ATEX zoning, for security of people as well as security of the process itself.
Safety of personnel is an important issue due to the harmful effect of EtO on humans. Polluted areas need to be alarmed using gas detectors set up at different locations to monitor any leak. Visual and audio alarm systems need to be provided. The system must inform any operator when a sterilization cell contains EtO.
When this toxic gas is removed from the room it needs to be treated using thermal burners, scrubbers or oxidation for environmental protection or be transported to an alternate facility for treatment. Most EtO sterilization lines involve three different stages.
These can be separated into three different cells depending on the size or amount of devices to treat:. First, products need to go through a pre conditioning phase to make micro organisms grow. The batch load goes through a dwell time under a controlled environment of:. Then the load goes through a long and complex sterilization cycle. Requirements of such a system are:. During this cycle, accurate temperature control is important and a heating jacket is used.
As the overall duration of this cycle is around 60 hours, high availability of the system is vital and system redundancy is required. Doubling sensors, actuators and controllers as well as changeover facilities on these components, helps to ensure the product is sterilized even on hardware or software failure. After the doors have been shut down and sealed correctly, the cycle can be started either manually or automatically.
Validating sterilization processes by ethylene oxide
If any problem with door sealing is detected the cycle is interlocked and cannot start. Security interlocks are also used between air and EtO valves. Control of vacuum and pressure is also required.
Due to the toxic effect of EtO, water ring rotary pumps are used. The vacuum process needs to perform the emergency evacuation phase for a fast evacuation of gas.