What is Sterilization using Ethylene Oxide?

The gas ethylene oxide, sometimes referred to as EO or EtO, is frequently used to chemically sterilize medical equipment and supplies. One powerful and deeply penetrating alkylating agent is ethylene oxide. It is a very effective sterilizing agent because of these qualities. But ethylene oxide can potentially cause cancer at certain concentrations. Microorganisms are killed by ethylene oxide sterilization, which involves exposing them to ethylene oxide gas in a vacuum and humidity. EtO can be utilized alone or in conjunction with carbon dioxide.

Ethylene Oxide (EtO) Residuals: What Are They?

Ethylene oxide’s absorption into some materials and its reactivity with water or other material components to generate harmful leftover chemicals are the main problems with utilizing it for sterilization.

Residual ethylene oxide is:

• Ethylene oxide (EO or EtO)
• Ethylene chlorohydrin (ECH)
• Ethylene glycol (EG)

Both humans and the ecosystem are at risk from these leftover chemicals. Ethylene chlorohydrin is created when ethylene oxide and chloride molecules combine, whereas ethylene glycol is created when ethylene oxide and water mix.

Why Is Residual Testing for Ethylene Oxide Necessary?

At some concentrations, ethylene oxide residues can be harmful and cause cancer in people. To ensure patient safety when using medical devices and products, ethylene oxide-sterilized products must adhere to stringent ethylene oxide residual limitations. Here are the most recent ISO 10993-7 EtO residual limits. EtO and ECH limits are provided. Items that are within the ECH and EtO limitations are likewise within the EG limits. Depending on how long a medical device is in contact with a patient, devices undergoing ethylene oxide (EO) sterilization may be classified into multiple EtO limit exposure categories.

Which Items Need to Have Their Ethylene Oxide Residuals Tested?

EtO residuals testing is necessary for any ethylene oxide-sterilized objects that come into direct contact with a patient. EtO residual testing is not necessary if your product or gadget is not in close physical touch with the patient.

If in doubt, find out if ethylene oxide residuals testing is necessary for your product. Choose the most appropriate ethylene oxide extraction technique for your device and learn how to get your samples ready for testing if your device does need to be tested for ethylene oxide residuals.

What Are USP 1115, USP 1116, And USP 1211’s Main Distinctions?

Nonsterile monitoring and manufacturing circumstances covered by USP 1115 are exempt from the same quality standards and limitations as the aseptic manufacturing settings covered by USP 1116. Terminal sterilization, the third kind of sterilizing procedure, is covered by USP 1211. By a final sterilization process that ensures a measurable safety level, the majority of terminally sterilized products meet the same sterility requirements as aseptically treated products without going through aseptic processing. Aseptic processing is far more expensive than terminal sterilization. Therefore, nonsterile production followed by terminal sterilization processing, rather than aseptic processing, will be used to meet FDA sterility criteria for the majority of items.

How Do You Conduct Residual Testing for Ethylene Oxide?

There are two methods for EtO residual analysis that are used to determine the kind and quantity of EtO residuals in your medical device. The two techniques for assessing EtO residuals are exhaustive extraction and simulation-use extraction. It is not required to evaluate a gadget using both testing procedures. The ISO 10993-7 requirements for EtO residual testing can be satisfied by using either exhaustive extraction or simulated-use.

Simulated-Use Extraction for Residuals of Ethylene Oxide

“Residue levels available to the patient or user from devices during the routine use of a device with water extraction to simulate product use” is what ISO 10993-7 defines as simulated-use extraction. When a portion of an EtO-sterilized device—rather than the full device—will come into touch with a patient, this extraction technique is employed. The fraction of the EtO-sterilized device that a patient would come into contact with during regular product use will thus be replicated by the simulated-use extraction. A transfer reduction factor approach can be used to estimate the amount of EtO residual that is transported to the patient for big, surface-contacting devices (such drapes or gowns). The surface-area-proportion or weight basis may be used for the transfer reduction factor technique (Annex E of ISO 10993-7).

Complete Ethylene Oxide Residual Extraction

“Until the amount of EtO or ECH in a subsequent extraction is less than 10% of that detected in the first extraction, or until there is no analytically significant increase in the cumulative residue levels detected,” according to ISO 10993-7, is what is meant by exhaustive extraction. This extraction technique estimates the majority of EtO residue that a patient will be exposed to while using the device and works best when the complete device would come into touch with the patient. Until the requirements for comprehensive extraction and device use (limited, prolonged, and permanent exposure) are satisfied, extractions are usually carried out every 24 hours. Extensive extraction may not be feasible for devices that are huge or complex. In these cases, the EtO residuals for the entire device may be extrapolated by extracting representative parts of the device. Continue extraction until the increase in the cumulative yield of the analyte extracted is minimal in relation to the analytical uncertainties, especially if the yield of the first extraction is limited (as is the case with devices that release analyte slowly or with little residue).

Calculations of Allowable Limits

The maximum amount of tolerable exposure to a specific toxin, like ethylene oxide, is known as the allowable limit (AL). The amount of AL is measured in milligrams per day. Tolerable exposure (TE) and a benefit factor (BF) combine to form AL. Body mass (BW), usage factor (UTF), and TI are multiplied to get TE. Milligrams per day (mg/d) is the unit of measurement for TE.

AL = TE x BF

Where:

TE = tolerable exposure

BF= benefit factor

And: 

TE = TI x BW x UTF

Where: 

TI = tolerable intake (mg/kg/d)

BW = body weight (kilograms (kg))

UTF = utilization factor

Since using an EtO-sterilized device (as opposed to one sterilized in another way) does not significantly improve health, the BF is set at 1. Therefore, the acceptable exposure is the same as the permissible limit for EtO residuals. A benefit factor of 1 has exceptions, which are covered in ISO 10993’s Annex F.

For limited exposure (the first 24 hours of exposure), the current permissible limits for ECH and EO are 4 mg/d and 9 mg/d, respectively.

EO at 0 mg/d and ECH at 2 mg/d for prologued exposure (one day to thirty days)

For prologued exposure (greater than 30 days of exposure), take 1 mg/d of EO and 0.4 mg/d of ECH.

In brief

All things considered, ethylene oxide sterilization is a substitute for conventional thermal sterilizing techniques (such as steam). However, at certain concentrations, ethylene oxide residuals (EtO, ECH, and EG) are harmful and carcinogenic to people. To ensure patient safety when using ethylene oxide-sterilized products that come into physical touch with patients, these products must pass ethylene oxide residual testing and adhere to stringent ethylene oxide residual limitations. To satisfy the ISO 10993-7 requirements for EtO residual testing, either simulated-use or exhaustive extraction is enough for identifying the quantity and kind of EtO residuals in your medical device. When only a portion of the EtO-sterilized device—rather than the full device—will come into touch with a patient, the simulated-use extraction method is employed. The fraction of the EtO-sterilized device that a patient would come into contact with during regular product use will thus be replicated by the simulated-use extraction. When the complete device will come into touch with a patient, the exhaustive extraction method works best because it estimates the majority of EtO residue that the patient would be exposed to while using the device. The maximum amount of tolerable exposure to a specific toxin, like ethylene oxide, is known as the allowable limit (AL). For limited exposure (first 24 hours of exposure), the current permissible limits for EtO and ECH are 4 mg/d of EO and 9 mg/d of ECH; for prologued exposure (one day to thirty days of exposure), they are 2.0 mg/d of EO and 2 mg/d of ECH; and for prologued exposure (more than thirty days of exposure), they are 0.1 mg/d of EO and 0.4 mg/d of ECH. All things considered, make sure the contract testing company you select can offer the proper ethylene oxide residual testing and sterilization validations for your particular medical device and product requirements.