How To Use Dry Heat Sterilization For Depyrogenation Of Medical Devices
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 viruses that have the potential to reproduce. Thus, sterile products that undergo sterilization are often chemical, heat or radiation sterilized. Sterilization kills any microorganisms inside the products obtained during manufacturing. Sterilization occurs after the product is placed in its final packaging for chemical, heat, or radiation sterilization. The last sterilization process after manufacturing is known as terminal sterilization.
How do thermal sterilization methods work?
Heat-based sterilization methods kill microorganisms by denaturing proteins within the cells.
Thermal sterilization lethality depends on:
- Degree of heat exposure
- Duration of heat exposure
- Moisture level
What is sterilization by dry heat?
Sterilization by dry heat uses exceptionally high temperatures, 170◦C at minimum, to inactivate microorganisms. Dry heat kills microorganisms by oxidation (cell bursting) because of the high temperatures experienced during sterilization.
What items can be sterilized by dry heat?
Items typically sterilized by dry heat are glassware, metal parts, oils, and some dry powders.
How is sterilization by dry heat performed?
Sterilization by dry heat is a simple process where loaded items are placed into a heating cabinet or conveyor tunnel. Items to be sterilized are then exposed to high temperatures for an extended time, and filtered air blower fans enable the heat to be uniformly distributed in the sterilizer. Fans or blowers also aid heat circulation by minimizing air density issues and keeping air from stratifying. Temperatures experienced by items under dry heat sterilization often vary from 170◦C (the minimum temperature for microbe sterilization) to 250◦C (the minimum temperature for depyrogenation). During sterilization by dry heat, materials expand during heating and contract during cooling. Thus, all openings must be securely covered to protect microorganisms from being drawn into materials during contraction.
As mentioned above, sterilization by dry heat is performed in cabinet ovens or conveyor tunnels. In these systems, temperature, time, and blower speed are controlled during sterilization. In cabinet ovens, HEPA filtered air flows across the load, moved by a blower. Though HEPA filters remove most particulates, there is always a risk that particulate matter generated from the heat source could collect on the sterilized load. In order to prevent particulates from entering the cabinet and consistent temperature during sterilization, the cabinet dryer door must be appropriately sealed before sterilization. Note that the size of the cabinet oven chamber is limited. Limited chamber size, along with manual loading and unloading, reduces the processing rate for dry heat sterilization. Dry heat sterilization processing rates are much higher for tunnel sterilizers. Tunnel sterilizers are dry heat conveyor systems. In the conveyor system, items are sterilized and depyrogenated as they move from heating zones through cooling zones. The heat source for a dry heat sterilization tunnel is either convection or radiant heat. Cooling zones contain vertical laminar airflow units under HEPA filtration. Tunnel sterilizers contain a stainless-steel conveyor belt. The conveyor belt often moves nonsterile containers through the dry heat sterilization cycle and onto a collection table for immediate sterile product filling. Tunnel dry heat sterilizers are primarily used to sterilize glass containers and are part of a sterile fill system. Tunnel sterilizers, like cabinet ovens, may generate particles from the heating source. Where tunnel sterilizers provide advantages in dry heat sterilization loading and unloading speeds, tunnel sterilizers are more challenging to validate than cabinet ovens, as it is tricky to control uniform heating throughout the entire conveyor system.
What is depyrogenation?
Depyrogenation is a process that removes pyrogens. The most prevalent and problematic pyrogens are the bacterial endotoxins found in the outer cell walls of gram-negative bacteria. Thus, depyrogenation is a process that will either destroy or remove bacterial endotoxins. Depyrogenation by dry heat is the process of destroying bacterial endotoxins through high heat exposure.
How is depyrogenation by dry heat performed?
Dry heat is commonly used for the depyrogenation of heat-stable materials. Dry heat depyrogenation depends upon time and temperature. Depyrogenation processes are performed at temperatures ranging from 170°C up to about 400°C. Understanding the total thermal input makes it possible to predict the depyrogenation efficacy of dry heat processes at various times and temperatures. Since bacterial endotoxins are more resistant to the effects of dry heat than bacterial spores, depyrogenation methods also sterilize the materials they depyrogenate.
Dry heat depyrogenation uses air first to heat and then to cool items. Due to the heat capacity of dry air, loaded items are slowly heated and cooled during dry heat treatment. Items in the dry heat ovens must be placed in the same locations every time for depyrogenation cycles to be valid due to the limited heat capacity of air. Indeed, varying load mass and product distribution can result in dry heat processing variability. Dry heat depyrogenation, like dry heat sterilization, uses a combination of temperature sensors and thermocouples to regulate temperature and dwell time to the levels needed to kill the endotoxin load on incoming materials. By convention, the z-value for dry heat depyrogenation ranges from 45°–55°C. This z-value is the rate at which the depyrogenation destruction rate varies as a function of temperature change.
The dosimetric measurement for dry heat depyrogenation processes is measured by FD units. An FD = 1 is defined as the depyrogenation effect achieved by 1 minute of heating at 250°C. FD calculations are used to compare dry heat depyrogenation effects during processes that have varying temperatures. A sum of the instantaneous temperature contributions over the entire depyrogenation process will calculate the overall process efficacy (in FD ). The process efficiency can be calculated using the process start time, process end time, temperature at each time increment, and the time interval between temperature measurements. Commercial software enables companies to calculate FD of processes by integrating the total FD accumulated during a treatment. FD calculations are used during validation, validation maintenance, and any change control to the process.
Summary
Overall, depyrogenation is a process that removes pyrogens. The most prevalent and problematic pyrogens are the bacterial endotoxins found in the outer cell walls of gram-negative bacteria. Depyrogenation by dry heat is the process of destroying bacterial endotoxins through high heat exposure. Dry heat is commonly used for the depyrogenation of heat-stable materials, as depyrogenation processes are performed at temperatures ranging from 170°C up to about 400°C. Since bacterial endotoxins are more resistant to the effects of dry heat than bacterial spores, depyrogenation methods also sterilize the materials they depyrogenate. All in all, ensure you choose a contract testing organization that can provide appropriate bacterial endotoxin testing and sterilization validations for your product needs.
Ethide Labs is a contract testing organization specializing in Sterilization Validations. Ethide Labs also offers Bioburden Testing, Microbiology Testing, Bacterial Endotoxin Testing, EO Residual Testing, Sterility 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. 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. <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>).
United States Pharmacopeial Convention. <1228.1> Dry Heat Depyrogenation. Rockville, MD, USA. 2021. (USPC <1228.1>)
