1. ETHYLENE OXIDE STERILIZATION VALIDATION
Pacific BioLabs Inc.
(510)

2. EO ADVANTAGES Highly effective against most microbes Highly diffusive
Compatible with a wide variety of materials in devices and packaging

3. EO DISADVANTAGES Complex process Longer turn-around times
BI Testing
Residual disipation
Safety concerns
Flammable
Explosive
OSHA concerns
Carcinogen
EPA concerns
Emissions

4. DETERMINE THE STANDARD
AAMI/ISO ed
“Sterilization of health care products – Ethylene oxide - Part 1: Requirements for the development, validation and routine control of a sterilization process for medical devices”
Europe – EN 550

5. EO GUIDANCE DOCUMENTS AAMI Technical Information Reports (TIR’s)
14 Contract sterilization
15 Equipment
16 Microbiological aspects
20 Parametric release
28 Product adoption and process equivalency

6. EO PROCESSING STEPS Preconditioning/conditioning
Exposure to RH and temperature
Ensure uniformity of these conditions
Sterilization cycle
Exposure to EO gas
Aeration
Dissipation of remaining gases

7. DECISIVE PROCESS PARAMETERS
Gas concentration
>400mg/L
Temperature
~100 – 140ºC
Relative humidity
~35 – 80%
Exposure (dwell) time
2 – 10 hours

8. DEEP VACUUM CYCLE

9. SHALLOW VACUUM CYCLE

10. FACTORS AFFECTING CYCLE SUCCESS
Bioburden
Product/package properties
Loading configuration
Cycle parameters

11. EO VALIDATION OVERVIEW
Process development
Product compatibility
Commissioning
PQ – Physical
PQ – Microbiological
Certification
Revalidation

12. PROCESS CONTROL Must assure that validated process parameters are met
Temperature RH
Gas concentration
Biological indicators are used to demonstrate lethality
Microprocessors are used to control process

13. RELEASE MECHANISMS
Documentation showing that processing specification are met
Successful results of tests
Sterility of BI
EO residues
Packaging
Pyrogens

14. PARAMETRIC RELEASE BIs not used in release Validation more involved
Routine control more rigorous
AAMI TIR20:2001 “Parametric release for ethylene oxide sterilization”

15. PRODUCT COMPATIBILITY
Post sterilization testing for
Device functionality
Package integrity and strength
Residue dissipation rates
Impact of re-sterilization

16. COMMISSIONING Equipment specifications/diagram Calibration records
Profiles for
Preconditioning (temp. and RH)
Aeration rooms (temp.)
Empty chamber temperature distribution

17. PQ - PHYSICAL
Profiles within loaded preconditioning and aeration areas
Loaded chamber temperature distribution studies
Diagrams showing load configuration, thermocouple and BI placement

18. PQ - MICROBIOLOGICAL
Records of performance runs (sub-lethal, half, and full cycles)
Diagrams of load configuration with BI and thermocouple placement
BI test result
Sterility test result of product
B/F testing

19. INITIATING A VALIDATION
Determine the standard
Insure appropriate packaging
Determine worst case load
Determine challenge device
Internal
Process challenge device (PCD)
Select Validation Method
BI release
Parametric

20. CHALLENGE DEVICES Internal Challenge Device (ICD)
Most difficult to sterilize devices seeded with a BI in the most difficult to sterilize location
PCD
An external BI test pack that replaces the internal challenge device
Should be an equal or more difficult challenge to the process than the ICD
Developed using comparative resistance studies

21. PARAMETRIC RELEASE Benefits Faster TAT
Useful if extended aeration not required
Considerations
More complicated validation
Minimum of 6 or 7 sub lethal cycles
Direct measurement of EO, RH and temp.
Load configuration becomes more critical

22. BI RELEASE BI Overkill (most common) Demonstrate 10-6 SAL
Assume bioburden has lower population & resistance than BI
Need a > 12 Spore Log Reduction (SPL) of BI
Combined BI/Bioburden
Absolute Bioburden (rarely used)

23. BIOBURDEN TESTING Test 10 samples randomly selected
Determine recovery factor – validation
If bioburden >100, comparative resistance study required
If bioburden <100, you are OK

24. SAMPLE PLACEMENT
Protocol must detail the number and location of all samples in load
BI’s
Product sterility (if applicable)
ETO residuals
Product functionality
Package integrity
LAL

25. VALIDATION CYCLES
Fractional cycles
Half cycles
Full cycles

26. FRACTIONAL CYCLE
Must be run when bioburden >100 and no comparative resistance studies are performed
Desired cycle time must results in some positive
BI and sterile product in sterility tests
A minimum of 20 product sterility samples
(10 TSB, 10 FTM)
Product sterility samples must be placed
adjacent to BI

27. HALF CYCLES
Three half cycles must be run in production chamber with a gas dwell time half the full cycle dwell time
The following must be placed in load
Temperature and humidity sensors
Internal BI
External BI (optional)
Product sterility samples if comparative resistance studies not done or inconclusive

28. FULL CYCLE A minimum of one full cycle is required for the Micro PQ
Three cycles are required to meet residual requirements
The following samples are included
EO residual
Product functionality
Packaging integrity
External BI (routine release BI)
LAL

29. EO RESIDUAL TESTING
1 - 3 samples of each type should be tested at a minimum of 3 time intervals from processing (Ex. 1, 3, & 5 days)
This must be done after 3 full cycles
Testing for EO and ECH
Samples must be shipped frozen

30. ACCEPTANCE CRITERIA Bioburden must be in control
Product sterility all neg after half cycles
Acceptable B&F test
BI Testing
Fractional cycle - some should grow
Half cycle - all negative
Full cycle - all negative

31. ACCEPTANCE CRITERIA (cont.)
Temperature sensors <10°C
Humidity sensors <30%
EO residual
Product functionality
Package integrity
LAL

32. REVALIDATION
Annually the status of the sterilization validation must be reviewed
Physical and biological revalidation must be conducted every two years
Inspection of
Product design and packaging
Chamber performance, calibration and maintenance

33. REVALIDATION (cont.)
If there have been changes in product design, packaging, or chamber performance, a physical and biological revalidation may be required
Validation should consist of a minimum of one half cycle and one full cycle

34. REFERENCES
AAMI/ISO ed. Sterilization of health care products- Ethylene oxide- Part 1: requirements for the development, validation and routine control of a sterilization process from medical devices
AAMI TIR No. 16:2000, Process development and performance qualification for ethylene oxide sterilization – Microbiological aspects
AAMI TIR No. 29:2001, Parametric release for ethylene oxide sterilization
AAMI TIR 28:2001, Product adoption and process equivalency for ethylene oxide sterilization

35. THANK YOU
Q & A