In the healthcare industry, where safety and precision are paramount, the sterilization of medical devices is vital for ensuring patient care. Among various sterilization methods, ethylene oxide (EO) sterilization is widely recognized as a critical process for eliminating harmful microorganisms from sensitive medical devices without compromising their functionality. EO, a colourless and odourless organic compound with the chemical formula C₂H₄O, can exist as a liquid or gas depending on the temperature. Its boiling point of 10.4°C is highly toxic and flammable, requiring stringent handling and safety measures. Its effectiveness and compatibility with heat-sensitive materials make it an indispensable method for ensuring the safety and reliability of medical devices.
Here are Key highlights
- Comprehensive Validation Process
Installation Qualification (IQ): Confirm that sterilization equipment is installed correctly and operates as intended.
Operational Qualification (OQ): Verifying that the equipment functions consistently within specified parameters.
Performance Qualification (PQ): It includes Physical PQ and Microbiological PQ Ensuring that the sterilization process reliably achieves the desired results under actual conditions.
Physical PQ: Physical PQ demonstrates that all the acceptance criteria (temperature, humidity, EO concentration) are met throughout the time estimated for routine sterilization. Physical PQ also demonstrates that all the acceptance criteria (temperature, humidity, EO concentration) are met for a minimum of 3 consecutive runs, meaning that the process is reproducible. Physical PQ can be combined with microbiological PQ.
Microbiological PQ: Microbiological PQ demonstrates that the sterilization process is effective. it makes the products sterile.
There are two steps before doing a PQ
- Select a Process Challenge Device (PCD)
- Select the reference load or the worst-case load
- Critical Process Parameters
Critical parameters that must be controlled and monitored to ensure effective sterilization.
Gas concentration: Gas concentration can be measured using the gas low PV=nRT, by measuring the pressure or temperature. It is also possible to measure directly using a sensor. As EO concentration increases, lethality increases up to a plateau point.
Temperature: Higher temperatures accelerate microbial inactivation (Q10 Effect: every 10°C rise doubles the inactivation rate)
Relative humidity: Humidity helps transfer heat to the product/packaging. Humidity increases the lethality of the process. Two ways in which moisture can be introduced – preconditioning (outside the chamber) or by injecting steam into the chamber (conditioning). Typical range is 30-80%
Exposure time: Time ranges from 2 to 6 hours. It depends on the type of product like what is the density, and how well it can absorb EO. Exposure time depends on the time taken for the gas to reach the difficult-to-reach areas of the product.
- Stages of the EO sterilization process
Precondition: Before the actual sterilization, devices undergo preconditioning to prepare them for effective sterilization. This stage involves:
Temperature and Humidity Stabilization: Devices are exposed to controlled conditions to ensure uniform penetration of EO gas during sterilization.
Timeframe: Preconditioning can last several hours to a day, depending on the device type and packaging.
Sterilization cycle: This is the core stage of the process, where EO gas is introduced to eliminate microorganisms. Key aspects include:
Vacuum and Gas Introduction: The sterilizer chamber is evacuated to remove air, and EO gas is introduced under specific pressure and concentration.
Temperature and Humidity Control: Maintaining optimal levels is critical for EO gas penetration and microbial inactivation.
Exposure Time: The duration of EO exposure varies depending on the device’s material, design, and sterility requirements.
Aeration: After sterilization, devices undergo aeration to remove residual EO gas and ensure safety for handling and use.
Duration: Aeration times can range from hours to days, depending on the device material and regulatory requirements.
Temperature: Aeration chambers are maintained at elevated temperatures to accelerate gas removal.
- Selection of the product configuration
The success of Ethylene Oxide (EO) sterilization largely depends on the proper selection and preparation of product configurations. Since EO sterilization involves gas penetration into complex surfaces and packaging, optimizing the product configuration is critical to ensure effective microbial inactivation without compromising product safety or integrity. It includes devices Density, Dimension, Material Composition, number of lumens, packaging type, and placement of devices.
- Advantages & Disadvantages
Advantages: Materials are not exposed to high heat, moisture & radiation, A Wide variety of products can be sterilized using EO gas due to low reactivity, Products can be sterilized in their final packaging.it can penetrate deep since it is highly diffusive.
Disadvantages: Toxic and inflammable, longer cycle times, Several steps in the process. Hence continuous monitoring & automation are required, May react with metals, and Toxic residuals can remain.
- Sterility assurance level (SAl):
SAL: the probability of a single viable microorganism occurring on an item after sterilization. A SAL of means the probability that there is 1 viable microorganism out of 1000000.
- Residual EO
Specifies acceptable limits for residual EO and its by-products (ethylene chlorohydrin and ethylene glycol) on medical devices.
For limited-contact devices: ≤ 4 mg/device.
For prolonged-contact devices: ≤ 2 mg/device.
For permanent-contact devices: ≤ 0.1 mg/device.
- Contents of lab report:
Method of extraction
Method of test (Gas Chromatography is the most common method)
Residual Values in mg/ml
The detection limit of the test
A validation report of the analytical test method
- Conclusion:
In the healthcare industry, Ethylene Oxide (EO) sterilization remains a cornerstone for ensuring the safety and efficacy of medical devices, particularly those sensitive to heat and moisture. Its unparalleled ability to penetrate complex surfaces and packaging while effectively eliminating microorganisms makes it indispensable. However, achieving optimal results requires meticulous adherence to critical parameters, including gas concentration, temperature, humidity, and exposure time. Through comprehensive validation processes like IQ, OQ, and PQ, and rigorous monitoring of residual EO levels, manufacturers can ensure compliance with safety standards and deliver sterilized products that meet the highest levels of sterility assurance.
Reference:
ISO 11135:2014Sterilization of health-care products — Ethylene oxide — Requirements for the development, validation, and routine control of a sterilization process for medical devices.
Author:
Anjali Kantesariya (Biomedical engineer)
Jr. regulatory consultant-Medical Device.