Process performance validation is to demonstrate that the sterilization process consistently meets the design criteria. Performance validation is part of the sterilization process validation cycle and includes the following two parameters: 1. Physical validation: This includes temperature distribution and heat penetration and verifies that the desired FPHY is consistently achieved during the loading period. 2. Biological validation: With appropriate microbiological challenges, verifies that the desired FBIO is consistently achieved during the loading period by performing cycles.
Prior to performance qualification, qualification of previous requirements and changes must be completed and documented in accordance with the company’s sterilization approach and current regulations. These qualifications include:
Qualification of supporting equipment such as steam with appropriate quality testing and compressed air or coolers according to the type of load
Qualification of the sterilizer including design qualification, installation qualification, performance or start-up qualification and calibration of critical components such as control systems, monitoring devices and alarms
For the determining parameters in the sterilization process that affect sterilization and post-sterilization performance at each phase of the cycle
Definition of the load, load pattern and specification of each load used in the quality assurance studies.
Maximum and Minimum Loadings and Hard Autoclavable Options
Temperature map of the autoclave chamber and loading options to identify the appropriate location for biological and physical evaluation.
Physical and microbiological results are always at the forefront of sterilization validation. Information obtained from temperature and pressure measurements alone cannot confirm the specific conditions required for lethality in cases where steam penetration is difficult.
In particular, proper sterilization of items such as syringe barrels, needle tips, or membrane filters cannot be reliably confirmed by information obtained from physical measurements. Similarly, the failure of biological indicators without considering the physical parameters that destroy the bioindicator cannot provide sufficient evidence for the suitability of the cycle. The results of the bioindicator challenge should be accompanied by the physical results, and vice versa.
To determine the minimum acceptable cycle (MAC), both physical and biological components must be qualified. To ensure that the minimum acceptable cycle is consistently effective, routine performance cycles generally include a margin of safety, such as using higher temperatures or times. For initial quality assurance, alternative cycles should be performed to ensure repeatability of the sterilization process.
Typical quality assurance consists of three consecutive acceptable steps for each load. After successful quality assurance of a process, event-based requalification and time-based requalification should be performed.
Verification of physical quality
The first goal of quality assurance of the physical components of the device is to obtain physical data that proves that by continuing to operate intermittently, the required gas penetration that was considered during the cycle design is achieved.
Heat distribution
The main purpose of temperature distribution quality assurance is to verify uniform temperature distribution in the autoclave area and during loading. For temperature distribution measurements, temperature sensors should be placed in the loaded environment but should not be in contact with the loaded components or autoclave components such as shelves and racks. A detailed diagram of the sensor placement for each load should be prepared.
During the implementation of the principle of temperature distribution quality assurance, key and critical parameters should be confirmed and documented. In general, the acceptable ranges for these key parameters obtained from the implementation of temperature distribution quality assurance include the following:
1- Difference in temperature measurement by each probe
2- Temperature difference between probes
3- Temperature difference between probes and the set temperature of the device
Heat penetration
The heat penetration quality assessment indicates that the desired amount of heat is transferred to the materials or surfaces being loaded. The heat penetration data is used to calculate the FPHY. The heat penetration probes should be placed in cold spots between the parts and the points that heat up slowly and are difficult to sterilize. In addition, in the case of liquid loading, the probes are placed in the carriers randomly or according to a determined geometric pattern.
Temperature changes should be less than ± 1 ° C from the average chamber temperature. Temperature deviations of more than ± 2.5 ° C from the average chamber temperature may indicate damage or defects in the device components, which is very important and must be corrected quickly.
Steam penetration test
A Bowie & Dick test is performed to check the penetration of saturated steam into the test objects. Chemical indicator strips and cylinders are used for this test. Blackening of all parts of the strip indicates steam penetration.
Biological quality assurance
The purpose of biological quality assurance is to obtain biological information that confirms that sterilization cycles are killing microbes during the sterilization process. Biological quality assurance using microbial challenge involves the following steps:
1. An appropriate microbial challenge system is established based on the desired degree of microbial destruction determined during design.
2. Loading is performed under minimally sterilized conditions.
3. After the cycle is completed, the microbial challenge indicators are recovered.
4. Each microbial challenge indicator is incubated specifically in the appropriate medium.
5. The results are evaluated to ensure that the reduction in spore entry has been achieved and that the microbial challenge meets the predicted acceptable limits.
Biological Indicator Challenge Systems
To assess whether an autoclave cycle provides the necessary lethality to meet the design requirements, an appropriate microbial challenge is selected to provide meaningful results. To do this, the microbial challenge must be provided in an appropriate model. The biological indicator challenge system may vary for different loadings. The stability and size of the microorganisms must be appropriate for our purposes. This biological information is used to calculate the FBIO for the cycle.
Use and Placement of Biological Indicators
For cycles designed using the Overkill approach, the challenge system is typically Geobacillus stearothermophilus spores incubated on the actual items to be sterilized. Incubation is performed on suitable paper or substrate or commercial biological indicators.
The organisms used in the challenge in the qualification section often have lower resistance than the semilogarithmic G-spore. Therefore, the stearothermophilus model is used to characterize the bioindicator challenge system and, in addition, this model may be used to estimate the appropriate challenge for assessing the biological quality of a cycle regardless of the resistance of the selected organism.
Quality Assurance of Liquid Loading Cycles
To assess the biological quality of liquid loading, filled vials and caps are inoculated with the appropriate microorganism and the medium may be the product or a suitable substitute for the product. If the product contains an inhibitor or other antimicrobial agent that has properties that inhibit the growth of microorganisms, it may be necessary to use a suitable fluid as a suspension medium. The decision to use the product as a suspension medium should be made by studies that confirm that microbial growth is not inhibited by anything. The relevant microorganisms should be placed on the carriers in a random or geometric pattern among the loadings and also at any cold spots that may be encountered during the operation of the cycle. Heat penetration probes should be placed in the carriers adjacent to the inoculated carriers to properly monitor the incoming heat.
Hard/Porous Parts Cycle Quality Assurance
Biological indicators used for hard/porous part loads are usually obtained from commercial sources and may be mounted on paper, stainless steel, aluminum, or other suitable substrates. Bioindicator challenge systems are placed in areas where the least heat is applied to items that are considered difficult to sterilize. These may be, for example, between the folds of cartridge filters or in the center of the length of tubing that has the potential for air entrapment or on rubber stoppers that may be difficult for vapor to penetrate. To account for the proximity between FBIO and FPHY, the biological indicator should be placed close to the temperature measuring probes. When placing the probes and indicators, care should be taken not to increase or decrease the air escape or vapor penetration in a particular area. It may be necessary to include duplicate items in the load, one item containing a thermal probe and another a biological indicator, to obtain verifiable results.
