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.

Ethylene oxide residuals testing is essential when using ehylene oxide for sterilisation of medical devices to ensure that the levels of ethylene oxide (EO), ethylene chlorohydrin (ECH) and ethylene glycol (EG) are controlled and within the limits to avoid any risk to the patient during normal use of the products.

This is a requirement really stated in the international standard document ISO 11135 – 1: 2007. It is essential to test for EO residuals to avoid harmful effects like irritation, mutagenicity, carcinogenicity, organ damage and reproductive side effects.

When it ethylene oxide chosen as a sterilisation agent steps must be taken to minimise the exposure to EO residuals. ISO 10993-1 lays down the biological evaluation and testing requirements for each individually designed medical device. Over and above the requirements of ISO 10993 – 1 it is essential to meet the requirements of ISO 10993 – 7 which lays down the EO sterilisation process residual limits.

Together with the biological evaluation, ethylene oxide residual testing provides the justification that a medical device sterilised using ethylene oxide is safe for human use.

Part seven of ISO 10993 lays down the limits for residual ethylene oxide and ethylene chlorohydrin in individual EO – sterilised medical devices and the procedures for the measurement of EO residue and ECH residue.

Ethylene oxide treatment is one of the most common approaches for sterilisation of medical devices. It is important to develop validate and put in place procedures for routine control of ethylene oxide sterilisation processes and testing the resulting EO residuals in the products.

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).

How Is Ethylene Oxide (EtO) Residual Testing Performed?

EtO sterilized devices are placed into one or more of three exposure categories based on the duration of contact a medical device has with a patient. These categories are designed to protect patients against EtO-related cellular toxicity that can cause varying degrees of illness and tissue damage. The categories of EtO exposure are limited exposure (less than 24 hours), prolonged exposure (1 day to 30 days), and perpetual exposure (lifetime limit). Each category has specific limits (in milligrams) that must be met.

Two different analysis methods for EtO residuals are used to determine the amount and type of EtO residuals in your sterilized product. These methods are simulated-use and exhaustive extraction. Evaluation of a product via either simulated-use or exhaustive extraction is sufficient to meet the ISO 10993-7 standards for EtO residual testing. Evaluation of a product via both simulated-use and exhaustive extraction is not necessary.