Sterilization Validations Vs. Ethylene Oxide (EO) Residual Testing
What is sterilization?
Sterilization is any process that removes, kills, or deactivates all forms of life. Sterilization is related to the term sterile, which means a complete absence of viable microorganisms or microbes that have the potential to reproduce. Thus, sterile products that undergo sterilization are often chemically or heat sterilized after being placed in their final packaging. The chemical or heat sterilization kills any microorganisms inside the products (obtained during manufacturing and packaging). This chemical or heat sterilization process after final product packaging is known as terminal sterilization. Ethylene oxide (EO) residual testing, EO sterilization validation, sterilization validation services, and medical device sterilization validations will be covered in this article.
What is the difference between sterile and aseptic?
While both sterile and aseptic products will prevent microbial contamination following use, the processes by which microbial contamination is prevented are different. An aseptic process prevents contamination by the exclusion of microorganisms. In contrast, products created using a sterile process use a terminal sterilization process to kill live microbes before product use. Though the definitions for aseptic and sterile are not the same, sterile is used interchangeably with aseptic. Indeed, many products labeled as sterile are manufactured by aseptic processing rather than terminal sterilization.
What is ethylene oxide?
Ethylene oxide (EO) is a gas commonly used to sterilize medical devices and products chemically. The EO chemical sterilization process is used on materials that cannot withstand traditional heat and steam sterilization methods.
How do sterilization and ethylene oxide relate?
Sterile refers to verifying the absence of live microorganisms in a product or product-packaging system. Sterile is a condition that signals either the exclusion of microbes or the death of all viable microbes. The reason that viable (living) microorganisms are of concern for the sterility of medical products is that only live organisms can reproduce in the human body, on the product, or within the product itself to cause sickness or disease.
Bioavailable residual EO is toxic to cells and to the human body. Two other EO residual gases, ethylene glycol (EG) and ethylene chlorohydrin (ECH) are also toxic at certain levels. EO residual testing specifically tests for EO and ECH to ensure medical products and devices sterilized with EO will not be toxic to patients upon use. Thus, sterilization monitoring and ethylene oxide monitoring relate in that both microbes and EO residuals can result in patient illness from medical product use. Thus, ensuring low EO residual levels and sterilization of medical products is important for patient safety.
What are the differences between ethylene oxide (EO) residual testing and sterilization validations?
Sterilization validation services are used to ensure that the end sterilization process can appropriately kill any viable microorganisms in a sample. The most popular method for sterilization validation is an overkill method. Overkill methods are used to verify that a certain sterilization process can achieve a certain level of sterility even if the bioburden is higher than expected, in a difficult to sterilize location, or the sterilization cycle runs inefficiently. Depending on the goals of the sterilization validation services, either a full-cycle approach or a reduced level of treatment known as a partial cycle approach will be performed. An example of a partial cycle approach is a half cycle approach. Overkill sterilization validations are governed by ISO 17655-1.
EO residual testing is specific to quantifying EO and ECH residuals from EO sterilized medical devices or products. Two different methods are used for EO residual analysis when determining the amount and type of EO residuals in your medical device. The two methods for EO residual evaluation are simulated-use extraction and exhaustive extraction. Either simulated-use or exhaustive extraction is sufficient to meet the ISO 10993-7 standards for EO residual testing. Evaluation of a medical device via both simulated-use and exhaustive extraction is not necessary.
Why are ethylene oxide (EO) residual tests and tests for sterilization validations important?
Sterilization validation services are important quality control steps that verify that terminal sterilization methods effectively kill the live bioburden in a sample after manufacturing. As microorganisms exist on every surface (including our body), microbes can be accidentally introduced during the manufacturing or packaging process in many ways. Some of the most common examples are microbial contamination through the raw materials used, technicians, tubing/piping used to transfer product between development stages in a process, or the manufacturing environment itself. With such abundant sources of contamination, sterilization validations are imperative for verifying that the chosen sterilization process adequately kills the microbes that products and packaging accumulate during manufacturing.
Regarding EO residual testing, EO sterilized materials vary in their ability to absorb, retain and release ethylene oxide (EO). If your device isn’t in contact with the patient, there is no need to perform EO residual testing. However, if your device is in contact with the patient, EO 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 EO-related cellular toxicity that can cause varying degrees of illness and tissue damage. The categories of EO 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. You can find the particular EO and ECH residual limits for each exposure category here.
Summary
Overall, both EO residual testing and sterilization validations are imperative for regulatory approval of medical devices or products. These tests ensure that medical devices, products, manufacturing environments, and packaging are free from viable microbial contaminants, free from toxic residuals, and maintain sterility. Ensure you choose a contract manufacturing organization that can support you with appropriate EO residual testing and sterilization validations for your unique medical device or product needs.
Ethide Labs is a contract testing organization specializing in Sterilization Validations, Sterility Testing & EO Residual Testing. Ethide Labs also offers Microbiology Testing, Cytotoxicity Testing, Bacterial Endotoxin Testing, Bioburden Testing, Package Integrity Testing & Environmental Monitoring services for medical device companies and allied industries. Ethide is an ISO 13485 certified facility.
References
United States Pharmacopeial Convention. <1211> Sterility Assurance. Rockville, MD, USA. 2021. (USPC <1211>).
International Organization for Standardization. Sterilization of health care products- Moist heat- Part 1: Requirements for the development, validation, and routine control of a sterilization process for medical devices. Geneva (Switzerland): ISO; 2006. (ISO 17665-1:2006/(R)2016).
International Organization for Standardization. Biological evaluation of medical devices — Part 7: Ethylene oxide sterilization residuals. Geneva (Switzerland): ISO; 2008. (ISO 10993-7:2008).
