环氧乙烷灭菌工艺验证方案(英)

环氧乙烷灭菌工艺验证方案(英)内容摘要：

Loading in chamber Environmental Preconditioning Humidification Initial Evacuation Gas injection and Gas dwell Post exposure gas purge and air in bleed Heated Aeration No. of microanism on product Loading Pattern 1. Temperature of Load 2. Humidity of Load 3. Duration of preconditioning 4. 1. Evacuation rate 2. Number of nitrogen wash 1. Humidity of load 2. Temperature of load 3. Duration of humidification 1. Gas injection rate 2. Gas Concentration 3. Duration of Exposure 4. Temperature 5. Moisture content 1. Vacuum rate 2. Number of Nitrogen wash 1. Temperature 2. Aeration time TITLE: VALIDATION PROTOCOL FOR ETHYLENE OXIDE STERILISATION PROCESS VALIDATION PROTOCOL NO: SUT126 EFFECTIVE DATE: Page 9 Process Validation Procedure: Bioburden assessment: An understanding of the population of viable microanisms on a finished device (bioburden) is necessary and required to support the validation process. The bioburden assessment includes the total number of microanisms with their identities. The identification needs confirmation of gram stain characteristics and genus. It provides useful information and can be used to monitor changes over time and as a parison to anisms recovered during environmental monitoring. For determination of bioburden Refer to Appendix 2 Selection of Process Challenge Device (PCD): Process challenge device can be selected from the family representatives in order to reduce the number of products tested during the validation. Internal PCD is the most difficult to sterilize device seeded with a BI. For ease of sample removal an external PCD can be used in the validation. External PCDs are the external BI test pack that replaces the internal PCD. External PCD should serves as a resistance greater than or equal to that of the internal PCD. The external PCD is usually placed on the outside of the sterilization load between cases, just inside the case or under the stretch wrap. BI or PCD placement in the product load: After the product load challenge has been identified, the BI or PCD positioning and placement can be determined. BIs and PCDs should be distributed throughout the product load and, as much as possible, in the same orientation (., vertical). Following minimum number of BIs/PCDs to be included in each validation cycle (as per ISO 111351: 2020):  Up to 10 m3, the number of BIs is m3, with a minimum of 5.  From 10 m3 up to 100 m3, the number of additional BIs is one per additional cubic meter. Temperature and Humidity sensor in product load: For humidity check in preconditioning and conditioning/sterilization one humidity sensor per m3, with minimum number of sensor is two should be placed in sterilization load and it should include pallet centers, edges and surfaces. For temperature monitoring in validation one temperature sensor per cubic meter of product volume with a minimum of 3 sensors should be placed in the load. Load Temperature: ISO 111351:2020 requires that the minimum temperature of product permitted to enter preconditioning be determined. Load temperature prior to entrance to preconditioning should be determined at the lowest temperature zone. Direct TITLE: VALIDATION PROTOCOL FOR ETHYLENE OXIDE STERILISATION PROCESS VALIDATION PROTOCOL NO: SUT126 EFFECTIVE DATE: Page 10 placement of cold loads into preconditioning can result in excessive water condensation and load wetting, which can cause product damage and reduced lethality. In process validation it requires to simulate the worst condition to which the load will ever be exposed. The anticipated load temperature extremes can be simulated during validation by following techniques described in the appendices 1. Identification of the worst case location or cold spot: temperature is the easiest variable to measure and monitor, therefore temperature is used as an indicator of the worst case location in the sterilization load. During the preconditioning or conditioning phase temperature profile against time of the sterilization load measured and based on that data the worst case location or cold spot is identified. TITLE: VALIDATION PROTOCOL FOR ETHYLENE OXIDE STERILISATION PROCESS VALIDATION PROTOCOL NO: SUT126 EFFECTIVE DATE: Page 11 Process Qualification Runs: For validation, a microbial challenge will be performed to demonstrate the adequacy of the process to achieve the desired Sterility Assurance Level. Two methods are used a) Half cycle method (Overkill approach) b) Bioburden / BI method a) Half Cycle Method: During the bioburden assessment, if characterization of bioburden is not performed and the bioburden level is more than 100 CFU than the following steps are performed. In this method one fraction cycle, 3 onehalf cycle and one full cycle is performed. Place Biological Indicator (BI) with 10⁶ spores of Bacillus atropheus in the PCDs and product samples in each pallet with humidity and temperature sensor. (Place PCDs to cold spot of the product load) Load pallets of sterilization load in to the sterilization chamber Run fractional cycle according to prescribed cycle parameter (Use 188。 or ⅙ gas exposure time than full cycle) Aerate the product Remove the product sample and PCDs from the load Perform sterility test on product sample and BIs. Additionally perform Bacteriostasis/Fungi stasis test on the product sample. TITLE: VALIDATION PROTOCOL FOR ETHYLENE OXIDE STERILISATION PROCESS VALIDATION PROTOCOL NO: SUT126 EFFECTIVE DATE: Page 12 If product sterility samples show survival, repeat the run on new load with elevated g。