Environmental Monitoring 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.
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.
What is environmental monitoring for medical devices & products?
Environmental monitoring is the tools and techniques used to observe an environment, characterize an environment’s quality, and make sure that an environment meets established acceptance criteria.
How do sterility, ethylene oxide, and environmental monitoring relate?
Sterile refers to verifying the absence of live microorganisms in a product or product-packaging system. Sterile is either the death of all microbes or the exclusion of all live microbes in a product. The reason that viable (living) microorganisms are of concern for the sterility of medical products is that only live microorganisms 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 that medical products and devices that are sterilized using ethylene oxide gas will not be toxic to patients upon use. Thus, ethylene oxide relates to product sterility since it is an approved sterilization method.
When it comes to medical products and medical devices, environmental monitoring controls the microbial acceptance criteria for the manufacturing environments throughout the entire lifecycle of the product, from raw materials to end-use or expiration. Thus, environmental monitoring supports the sterility of a product through monitoring microbial contamination and keeping it at levels during manufacture that allows sterilization methods, like ethylene oxide sterilization or heat/steam sterilization, to kill all viable microorganisms before product use.
What are the differences between ethylene oxide (EO) residual testing and environmental monitoring?
EO residual testing is specific to quantifying EO and ECH residuals from EO sterilized medical devices or products. Two different methods for EO residual analysis are used to quantify 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. ISO 10993-7 standards for EO residual testing can be met by evaluating a device via either simulated-use or exhaustive extraction. Evaluation of a medical device via both simulated-use and exhaustive extraction is not necessary.
Sampling and testing (of the air, water, and surfaces) are key environmental monitoring components for preventing microbial contamination. Microorganism testing for environmental monitoring rarely requires the complexity and specificity of identifying the species and genus of different microbes. In this way, environmental monitoring sampling and testing differ from other traditional microbiology assays that directly test medical devices, packaging, or products. Environmental monitoring assesses the manufacturing environment where a product is manufactured. Thus, environmental monitoring is often used to confirm the microbe level of a product during manufacture to ensure that the terminal sterilization cycle for the product meets the requirements to kill all the microbes acquired during manufacture. This terminal sterilization cycle is often ethylene oxide for medical devices or products that cannot be steam or heat sterilized. Environmental monitoring is covered by USP 1115, 1116, 1211, and other assorted USP documents.
Why are ethylene oxide (EO) residual tests and environmental monitoring important?
Environmental monitoring is an important quality control metric and is particularly critical for verifying your medical device or product is devoid of microbes during various phases of manufacturing, packaging, transportation, and storage. Sampling and testing are key components of environmental monitoring for microbial contamination. Thus, environmental monitoring is imperative for preventing product-induced infections and mitigating contamination risk in manufacturing environments, especially aseptic manufacturing environments. Although not discussed in detail in this article, aseptic manufacturing environments rely heavily on environmental monitoring because aseptic processing requires excluding microorganisms from the manufacturing methods.
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 specific EO and ECH residual limits for each exposure category here.
Summary
Overall, both EO residual testing and environmental monitoring 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 and maintain sterility. Ensure you choose a contract manufacturing organization that can support you with appropriate EO residual testing and environmental monitoring for your unique medical device or product needs.
Ethide Labs is a contract testing organization specializing in EO Residual Testing & Environmental Monitoring. Ethide Labs also offers Bacterial Endotoxin Testing, Microbiology Testing, Cytotoxicity Testing, Sterility Testing, Bioburden Testing & Package Integrity Testing services for medical device companies and allied industries. Ethide is an ISO 13485 certified facility.
References
International Organization for Standardization. Biological evaluation of medical devices — Part 7: Ethylene oxide sterilization residuals. Geneva (Switzerland): ISO; 2008. (ISO 10993-7:2008).
United States Pharmacopeial Convention. <1115> Bioburden Control of Non-Sterile Drug Substances and Products. Rockville, MD, USA. 2021. (USPC <1115>).
United States Pharmacopeial Convention. <1116> Microbiological Control & Monitoring of Aseptic Processing Environments. Rockville, MD, USA. 2021. (USPC <1116>).
United States Pharmacopeial Convention. <1211> Sterility Assurance. Rockville, MD, USA. 2021. (USPC <1211>).
