Top ways to measure temperature for product sterilization and other regulatory tests
What instrument is most effective for pressure temperature sterilization, and what considered sterile for sterilization validation?
Under the strictest definition of sterility, an item or product is sterile when there is a complete absence of viable microorganisms (bacteria, yeasts, viruses, and molds). Regulatory-level sterility is defined by acceptance criteria based on calculated contamination probability. An acceptable level of contamination risk for most items is the probability of contamination for one in a million products. However, sterility criteria may be more stringent or lax depending upon the intended use of the medical device or product. Often, low temperature sterilization involves the use of chemical gas (such as ethylene oxide sterilization), radiation (gamma or electron beam), or filtration (for liquid products and biologics). High temperature sterilization is dry heat sterilization or steam sterilization (pressure temperature sterilization). As for what instrument is most effective for pressure temperature sterilization, autoclaves are the most common and popular pressure temperature instrument for high temperature sterilization. Ethylene oxide sterilizers (for low temperature sterilization) also have pressure temperature systems. Both autoclaves and ethylene oxide sterilizers use temperature sensors to detect and monitor heat during 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 with 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 (whether low temperature sterilization or high temperature sterilization) can consistently sterilize medical devices or products under “worst-case scenario” conditions. Sterilization equipment selection and functionality is important to the success of a sterilization validation. As mentioned above, autoclaves answer the question of what instrument is most effective for pressure temperature sterilization. Selecting an appropriate autoclave for any high temperature, steam sterilization validations will make the validation process smoother and more cost effective in the long run. For information on sterilization validation methods, see our article HERE.
How are sterilization validations performed?
Knowledge of sterilization technologies, instrumentation, and equipment is needed to control and verify sterilization process metrics appropriately. Representative biological indicators are selected and placed at strategic locations to cover “worst-case” microbial scenarios. Sterilization validations require multiple formally documented stages. General principles for validation programs (cleaning validations and the like) are applicable to all sterilization processes. Each sterilization mode (e.g., dry heat sterilization, wet heat sterilization, gaseous sterilization, etc.) has individual criteria that must be met. The first stage of sterilization validation is the process development stage. In the process development stage, operating parameters and controls used for the sterilization process are investigated and selected. The next stage is the installation qualification stage, which ensures that equipment controls and instrumentation are installed and calibrated appropriately. As part of the installation qualification, systems to regulate steam, water, and air should be verified and documented. The third sterilization validation stage is the operational qualification stage. Operational qualification makes sure that installed equipment functions within the set sterilization process parameters. After the operation of the equipment is verified, the performance qualification stage begins. Performance qualifications assess the sterilization of materials, items, and biological indicators that pass through the sterilization process under validation. Performance qualifications measure sterilization cycle controls and the effectiveness of the sterilization cycle in overcoming worst-case biological challenges. The fifth and final stage of sterilization validation is the routine process control stage. This final stage ensures that sterilization processes (low temperature sterilization and high temperature sterilization) are continuously monitored and controlled to maintain the efficacy of product sterilization.
Top temperature measurement devices for sterilization and other regulatory tests:
#1: Alcohol or mercury thermometers
Alcohol and mercury thermometers are everywhere and used for simple temperature measurements that do not require high-level temperature reading responsiveness. These thermometers determine the temperature based on mercury (or alcohol) liquid volume change. These basic thermometers are primarily used in a laboratory rather than for sterilization validations or product supply chain monitoring. Alcohol thermometers can have precision up to 0.01°C, but the alcohol volume must be large to measure temperatures of more than a few degrees. Mercury thermometers are typically used for temperatures from 0°C to 50°C with a precision of 0.1°C. Globally, mercury thermometers are discouraged due to the risk of mercury toxicity. Both alcohol and mercury thermometers are more fragile than other temperature-measuring devices. Their size, fragility, and temperature precision are the reasons why these thermometers are avoided for sterilization validation temperature measurements.
#2: Infrared (IR) thermometers
IR thermometers measure the radiant heat from items. IR changes as a function of an item’s temperature. The advantage of IR thermometers is that an object’s temperature can be determined away from the IR sensor. However, IR thermometers can give inaccurate (higher or lower) readings due to an object’s surface characteristics (e.g., black vs. white surfaces) or the use of the IR sensor at an improper angle. IR thermometers are currently used to take touch-free patient temperatures.
#3: Resistance temperature detectors (RTD)
Resistance temperature detectors determine the temperature based on the change in electrical resistance of a material as a function of temperature. Electrical resistance is measured in Ohms and measures an electrical circuit’s opposition (resistance) to current flow. RTD accuracy depends on the precision of the measured resistance. Thus, the quality of the electronics used in an RTD device determines its accuracy. Advantageously, RTDs are one of the most stable and precise temperature sensors. However, the accuracy of an RTD can alter as the device ages, as the electronic device components are affected by age and use. Thus, regular RTD calibration for equipment utilizing RTD thermometers is critical to ensure temperature-reading accuracy.
#4: Solid-state temperature detectors
Solid-state devices have a high degree of accuracy. Solid-state devices use an integrated circuit (thermistor), micromechanical system, or micro-electrical system effects to determine temperature.
#5: Thermistor temperature sensors
A thermistor is a device whose resistance varies with temperature. Thermistors are extremely precise and can identify tiny shifts in temperature over broad ranges of hot and cold. Thermistors are ubiquitous high-precision temperature sensors used in sensitive regulatory testing equipment, such as sterilizers.
#6: Thermocouple temperature detectors
Thermocouples determine temperature through the change in the junction potential of two dissimilar metals. Thermocouples utilize a variety of metal pairs to assess temperature, with each pair providing a different temperature detection range, accuracy, and precision. Like RTD devices, the thermocouple’s precision and accuracy depend on the quality of the electronics used to measure the voltage across both metals.
#7: Thermomechanical temperature sensors
Thermomechanical sensors determine the temperature based on the change in length of a solid material (often a spring). Indeed, thermomechanical sensors (such as springs) expand or contract as a function of temperature. The expansion or contraction can signal temperature shifts through moving a chart pen or opening and closing an electrical circuit. Many cold room temperature sensors utilize thermomechanical devices.
Summary
Overall, sterility can be assured only by using a validated sterilization process under current good manufacturing practices (cGMP). An acceptable level of contamination risk for most items is the probability of contamination for one in a million products. However, sterility criteria (for low temperature sterilization and high temperature sterilization) may be more stringent or lax depending upon the intended use of the medical device or product. Knowledge of sterilization technologies, instrumentation, and equipment is needed to control and verify sterilization process metrics appropriately. One of the pieces of instrumentation critical to ensuring the validity of a sterilization process for a medical device or product is temperature measurement devices. Temperature can be measured through a variety of means. The top USP-approved methods for temperature measurement are 1) alcohol or mercury thermometers, 2) infrared thermometers, 3) resistance temperature detectors, 4) solid-state temperature detectors, 5) thermistor sensors, 6) thermocouple detectors, and 7) thermomechanical temperature sensors. Resistance, solid-state, thermistor, and thermocouple devices are the most accurate temperature sensors and are the most used temperature tracking devices for sterilization processes. Steam sterilization is the most common form of high temperature sterilization. Autoclaves answer the question of what instrument is most effective for pressure temperature sterilization. Selecting an appropriate autoclave for any high temperature, steam sterilization validations will make the validation process smoother and more cost effective in the long run. All in all, ensure you choose a contract testing organization that can support you with appropriate sterility testing for your unique medical device or product needs.
Ethide Labs is a contract testing organization specializing in Sterility Testing and Sterilization Validations. Ethide Labs also offers Microbiology Testing, Bioburden Testing, Bacterial Endotoxin Testing, EO Residual Testing, Cytotoxicity Testing, Environmental Monitoring & Package Integrity Testing services for medical device companies and allied industries. Ethide is an ISO 13485 certified facility.
References
Michael J. Akers. Sterile Drug Products Formulation, Packaging, Manufacture, and Quality. Drugs and the Pharmaceutical Sciences. Informa Healthcare. 2010.
United States Pharmacopeial Convention. <1229> Sterilization of Compendial Articles. Rockville, MD, USA. 2021. (USPC <1229>).
United States Pharmacopeial Convention. <1118> Monitoring Devices Time Temperature And Humidity. Rockville, MD, USA. 2021. (USPC <1118>).
