ETO is a colorless gas that is flammable and explosive. The four essential parameters (operational ranges) are: gas concentration (450 to 1200 mg/l); temperature (37 to 63°C); relative humidity (40 to 80%) (Water molecules carry ETO to reactive sites); and exposure time (1 to 6 hours). These influence the effectiveness of ETO sterilization. Within certain limitations, an increase in gas concentration and temperature may shorten the time necessary for achieving sterilization.
The excellent microbicidal activity of ETO has been demonstrated in several studies and summarized in published reports.877 ETO inactivates all microorganisms although bacterial spores (especially Bacillus Atrophaeus) are more resistant than other microorganisms. For this reason, B. Atrophaeus is the recommended biological indicator.
Steps to an EO Validation
1. Process Challenge Device Selection
The process challenge device (PCD) is selected, providing a microbiological challenge system used to evaluate the delivered lethality of the selected process parameters. This is done by pacing a biological indicator (BI) within the product at a location where sterilizing conditions are the most difficult to achieve.
- Internal PCDs are usually medical products or devices selected by the manufacturer as one of the more difficult to sterilize products based upon product design and material composition and are used for validations.
- External PCDs are placed external to the product during routine processing to facilitate retrieval from the load after processing.
2. Reference Load Selection
A reference load selection is performed to identify the worst case load anticipated for routine sterilization. Items considered are product load density and volume, and product/packaging/load venting.
3. Protocol Generation
A protocol is generated documenting all validation activities, including:
- Scope &Objective
- Responsibilities
- Equipment Supplier Information
- Procedures (Acceptance criteria)
4. Ancillary Laboratory Testing
Ancillary laboratory testing is performed, including:
- Bioburden testing
- BI population verification testing
5. Physical and Microbiological PQ
The Physical and Microbiological PQ are typically performed in parallel with the Half Cycle Approach, structured as follows:
A Winter Conditions/Preconditioning Study may be done to simulate conditions in a trailer during colder weather months.
1 Fractional Cycle is performed with a minimal EO exposure time to validate the recovery of the biological indicator (BI) and establish the relationship between the BI and the natural product bioburden. The qualification consists of:
- Cycle performance analysis
- Product sterility testing
- Bacteriostasis/Fungistasis testing
- BI sterility testing (process challenge devices)
3 Half Cycles (4th half cycle needed if establishing a minimum load size) are performed to demonstrate the repeatability of a 6 spore log reduction of the BI utilizing minimum parameters, including one half of the intended routine exposure time. The qualification consists of:
- Cycle performance analysis
- BI sterility testing (PCDs)
- Load temperature/humidity monitoring
- EO concentration monitoring (parametric release only)
3 Full Cycles are performed for determination (and confirmation) of residues and for product/packaging functionality evaluations. The qualification consists of:
- Cycle performance analysis
- BI sterility testing (PCDs)
- EO/ECH residual testing (for 1X and 2X processing)
- Load temperature/humidity monitoring
- EO concentration monitoring (parametric release only)
6. Final Report
A final report is generated to:
- Document a review of the validation data
- Confirm the acceptability against the approved protocol for the sterilization process
- Approve the process specification
7. Revalidation
Revalidation of the established ethylene oxide process is performed on an annual basis. The revalidation consists of a review of the original validation data to confirm no changes have taken place. A reduced PQ (consisting of one-Half Cycle and one Full Cycle) may be performed if product or packaging changes have been made or if significant equipment or process changes have occurred. The reduced PQ is required every year for a parametric release process, but is commonly performed every other year for a BI release process.
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