What Are Sterilization Indicators & Sterilization Integrators?
What are integrators?
A physicochemical integrator is a device that measures at least one sterilization process parameter. System integrators can be sterility indicators for sterilization processes that use integrators for control (control integrators). Examples of sterilization parameters include radiation dosage, time, steam, humidity, and temperature. Integrators express a measurable value that can be correlated to microbial lethality either alone or in combination with other integrator measurements. Control indicators by definition provide measurable value by providing a measurable output value that is a time integral of an input value (such as radiation dosage). Examples of integrators include metric steam sterilization strips and dosimeters. Physicochemical integrators can provide primary evidence of sterilization process effectiveness.
What are indicators?
A physicochemical indicator is a device that provides visual evidence of exposure to at least one sterilization parameter. An example of a sterility indicator is autoclave sterilization tape. Unlike control integrators, sterility indicators cannot provide primary evidence of sterilization efficacy.
What are integrators and indicators used for
System integrators and sterility indicators are used to support sterilization process validations. Where sterilization validations aren’t needed, control integrators can provide some measure of the sterilization process’s efficacy.
What is sterilization, and why is it essential for sterile products?
Sterilization keeps patients safe from toxins and microbial illnesses when therapies or devices are consumed or used. Sterilization is any process that removes, kills, or deactivates all forms of life. Under the strictest definition of sterility, an item or product is sterile when there is the complete absence of viable microorganisms (bacteria, yeasts, viruses, and molds). Sterility is defined by regulatory acceptance criteria based on calculated contamination probability. An acceptable level of contamination risk for most items is the probability of a single contaminated product out of a million manufactured products. However, sterility criteria may be more stringent or lax depending upon the intended use of the medical device or product.
Commonly, sterile products undergo sterilization processes that utilize chemicals, heat, radiation, or filters. Sterilization kills any microorganisms products collect during manufacturing. A less common version of sterilization is vapor phase sterilization.
What are sterilization validations, and why are they important?
Since the sterility of a medical device or product is based on acceptance criteria, the process that a product or device undergoes to become sterile must be validated to prove that sterility acceptance criteria are consistently met. Sterility can be assured only using a validated sterilization process under current good manufacturing practices (cGMP). Sterility cannot be demonstrated by reliance on periodic sterility testing of final products alone. Thus, sterilization validations are tests that accumulate data about a sterilization process and statistically prove that the sterilization process can consistently and effectively sterilize medical devices or products under “worst-case scenario” conditions.
Physiochemical integrators and indicators are used in which sterilization processes?
Dry heat sterilization, steam sterilization, ethylene oxide sterilization, and radiation sterilization processes all use physiochemical integrators and indicators.
Dry heat sterilization
Dry heat sterilization is a heat-based method that kills microorganisms by denaturing proteins within the cells at 170ºC or higher temperatures.
Steam sterilization (sterilization by moist heat)
Steam sterilization (also known as moist heat sterilization) is performed in an autoclave. Moist heat sterilization destroys microorganisms on (or within) a product with steam under pressure. Steam kills the microorganisms by denaturing proteins within the cells. Steam sterilization is the most common method for medical device and medical product sterilization because it is non-corrosive, relatively fast, and inexpensive. Further, most healthcare facilities own one or more autoclaves on-site for reusable medical devices.
Ethylene oxide sterilization
Ethylene oxide (EO or EtO) is a gas commonly used to sterilize medical devices and products chemically. Ethylene oxide is a potent and highly penetrating alkylating agent. These characteristics make it an extremely effective sterilizing agent. However, at certain levels, ethylene oxide is also capable of causing cancer. Sterilization by ethylene oxide kills microorganisms through exposure to ethylene oxide gas under vacuum and humidity. EtO is used either as one hundred percent EtO, a carbon dioxide mixture, or a mixture with other gasses.
Radiation sterilization (sterilization by radiation)
Sterilization by radiation is a non-thermal sterilization method that functions by destroying microorganisms in a product with gamma radiation, beta particles (electron beam), x-ray, or ultraviolet light. Other than sterile filtration, sterilization by radiation is the only other sterilization method that doesn’t rely on elevated temperature to sterilize. Sterilization by radiation is an excellent alternative for products that cannot be sterilized with heat or chemicals.
How are integrators and indicators used?
System integrators and sterility indicators rapidly confirm sterilization cycle completion. Sterilization cycle confirmation is particularly critical for sterilization chambers with a single door, where non-sterilized and sterilized items can be mixed-up during loading and unloading. An indicator visually confirms that an item has experienced a sterilization process, whereas the control integrator can demonstrate adequate or inadequate exposure to sterilizing conditions. An indicator cannot provide information about the performance of the sterilization equipment (e.g., equipment calibration and cycle data). Also, except dosimeters for radiation sterilization, indicators are not acceptable as the only proof of sterilization cycle efficacy.
Unlike biological indicators, system integrators and indicators do not interact physically with any product or item to be sterilized. For example, steam indicator tape is used outside of wrapped products undergoing an autoclave cycle. The system integrator(s) and indicator(s) are positioned within the sterilization chamber such that they do not alter the effectiveness of the sterilization treatment but do provide a measurement for control of the sterilization process.
Summary
Overall, medical devices, products, and therapies must be sterile. Sterilization is any process that removes, kills, or deactivates microbes. Sterilization validation processes for dry heat, steam, ethylene oxide, and radiation sterilization use physiochemical integrators and indicators. A physicochemical integrator is a device that measures at least one sterilization process parameter. Examples of sterilization parameters include radiation dosage, time, steam, humidity, and temperature. Integrators express a measurable value that can be correlated to microbial lethality either alone or in combination with other integrator measurements. Thus, physicochemical integrators (such as dosimeters) can provide primary evidence of sterilization process effectiveness. Unlike integrators, physiochemical indicators cannot provide primary evidence of sterilization efficacy. A physicochemical indicator is a device that provides visual evidence of exposure to at least one sterilization parameter. An example of a physiochemical indicator is autoclave sterilization tape. All in all, ensure you choose a contract testing organization that can provide appropriate sterility testing for your product needs.
Ethide Labs is a contract testing organization specializing in Sterilization Validations and Sterility Testing. Ethide Labs also offers Microbiology Testing, Bioburden Testing, EO Residual Testing, Bacterial Endotoxin Testing, Cytotoxicity Testing, Environmental Monitoring & 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).
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).
Michael J. Akers. Sterile Drug Products Formulation, Packaging, Manufacture, and Quality. Drugs and the Pharmaceutical Sciences. Informa Healthcare. 2010.
United States Pharmacopeial Convention. <1211> Sterility Assurance. Rockville, MD, USA. 2021. (USPC <1211>).
United States Pharmacopeial Convention. <1228.1> Dry Heat Depyrogenation. Rockville, MD, USA. 2021. (USPC <1228.1>).
United States Pharmacopeial Convention. <1229> Sterilization of Compendial Articles. Rockville, MD, USA. 2021. (USPC <1229>).
United States Pharmacopeial Convention. <1229.9> Physicochemical Integrators And Indicators For Sterilization. Rockville, MD, USA. 2021. (USPC <1229.9>).
United States Pharmacopeial Convention. <1229.10> Radiation Sterilization. Rockville, MD, USA. 2021. (USPC <1229.10>).
