Dry Heat Sterilization is a sterilization process that can be used to terminally sterilize health care products, medical devices, equipment, components or bulk active pharmaceutical ingredients by exposing the items to a temperature of ≥ 160°C for a defined time.
For heat stable items, such as glassware or stainless steel equipment, a dry heat sterilization cycle can be run at 250°C to remove bacterial endotoxins from the items. This process is also referred to as Depyrogenation. Bacterial endotoxins are fever inducing compounds, or pyrogens, that are released when the cell walls of gram negative bacteria such as Escherichia coli are destroyed.
Validation of dry heat sterilization cycle(s) is required by ANSI, AAMI, ISO, USP and the FDA to ensure that all items that are required to be sterile or pyrogen free are able to consistently and reliably be sterilized to reduce the chance of introducing or spreading an infectious microorganism or pyrogen.
Installation Qualification (IQ)
Validation of a dry heat sterilization cycle begins with the execution of the Installation Qualification (IQ) protocol on the equipment (oven, tunnel, or cabinet) which will be used to perform the dry heat sterilization. The IQ protocol verifies and documents that the equipment is installed correctly and meets all of the manufacturer and user requirements. During the execution of the IQ protocol, the equipment drawings, calibration status of critical instruments, instrument and valve information, utility information, and standard operating procedures for the equipment are all confirmed.
Operational Qualification (OQ)
The next step in the validation of a dry heat sterilization cycle is the execution of the Operational Qualification (OQ) protocol of the equipment. The OQ protocol verifies and documents that the equipment is programmed and operating correctly, and is able to meet all of the manufacturer and user requirements. Execution of the OQ protocol involves verifying the parameters/settings (e.g. general system options, cycle length, airflow, sterilization temperature) of the dry heat sterilization cycle(s). It also ensures that the system alarms are operating correctly, that the equipment is functioning properly (e.g. verification that the control system functions as specified by the equipment manufacturer or system interlocks), and that the equipment is able to achieve and maintain the required sterilization conditions during the dry heat sterilization cycle(s).
Performance Qualification (PQ)
The execution of the IQ and OQ protocols covers the validation of the equipment. In order to validate a dry heat sterilization cycle, a Performance Qualification (PQ) protocol must be executed. The PQ demonstrates that the dry heat sterilization cycle(s) can repeatedly achieve the required Sterility Assurance Level (SAL) 1. In order to confirm that the necessary SAL can be reached, the dry heat sterilization cycle must be temperature mapped.
During the PQ, biological indicators should be placed throughout the chamber. Typically Bacillus atrophaeus biological indicators are used to demonstrate that the dry heat sterilization process can consistently deliver the required microbial inactivation. The biological indicators used must have a population of ≥ 1 x 106 organisms, and a D‑value of ≥ 2.5.
Incubation and enumeration of the biological indicators demonstrates whether or not the required SAL was reached. If the biological indicator population has been completely reduced (no growth of the biological indicators is observed after incubation), this indicates that the necessary SAL has been reached during the sterilization cycle.
For depyrogenation cycles, endotoxin vials containing a known amount of E. coli endotoxin should be used to demonstrate the required pyrogen removal. A 3 log reduction of the endotoxin level must be achieved in order for a depyrogenation cycle to be considered successfully validated.
To perform a temperature mapping, data loggers are placed throughout the equipment chamber (distribution data loggers) and the load being sterilized (penetration data loggers). In order to temperature map a depyrogenation cycle it is sometimes necessary to use thermal barriers to protect the data loggers from the extreme heat. All of the data loggers used should have at least a 3 point NIST-traceable calibration performed prior to use.
For lower temperature (≥160°C) dry heat sterilization, confirmation that the minimum SAL is attained is required. To do this, the temperature data recorded by the penetration data loggers during the cycle is evaluated to determine the lethality value (FH). Typically, the required FH is determined by the multiplying the D-value of the biological indicator used by 12.
In order for a dry heat sterilization or depyrogenation cycle to be considered validated, three successful temperature mapping tests must be completed with passing results for all of the predetermined acceptance criteria.
Mesa Validation Experts have the knowledge and experience needed to help you complete the IQ/OQ/PQ for your dry heat sterilization and depyrogenation equipment and processes. Our experts have your back, so you can rest assured that your dry heat sterilization or depyrogenation cycles are being completed – optimally, reproducibly, and consistently. Contact us today to learn more.
1 – The SAL is the probability of a single unit being non-sterile after it has been subjected to sterilization or the killing efficacy of a sterilization process. A typical SAL is 10-6, which is a 1 in 1,000,000 chance of a non-sterile unit.
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