ETHYLENE OXIDE
STERILIZATION VALIDATION
Pacific BioLabs Inc.
(510) 964-9000
info@PacificBioLabs.com
EO ADVANTAGES
Highly effective against most microbes
Highly diffusive
Compatible with a wide variety of materials in
devices and packaging
2
EO DISADVANTAGES
Complex process
Longer turn-around times
BI Testing
Residual disipation
Safety concerns
Flammable
Explosive
OSHA concerns
Carcinogen
EPA concerns
Emissions
3
DETERMINE THE STANDARD
AAMI/ISO 11135-01 4ed
“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
4
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
5
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
6
DECISIVE PROCESS PARAMETERS
Gas concentration
>400mg/L
Temperature
~100 – 140ºC
Relative humidity
~35 – 80%
Exposure (dwell) time
2 – 10 hours
7
DEEP VACUUM CYCLE
8
SHALLOW VACUUM CYCLE
9
FACTORS AFFECTING CYCLE SUCCESS
Bioburden
Product/package properties
Loading configuration
Cycle parameters
10
EO VALIDATION OVERVIEW
Process development
Product compatibility
Commissioning
PQ – Physical
PQ – Microbiological
Certification
Revalidation
11
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
12
RELEASE MECHANISMS
Documentation showing that processing
specification are met
Successful results of tests
Sterility of BI
EO residues
Packaging
Pyrogens
13
PARAMETRIC RELEASE
BIs not used in release
Validation more involved
Routine control more rigorous
AAMI TIR20:2001 “Parametric release for
ethylene oxide sterilization”
14
PRODUCT COMPATIBILITY
Post sterilization testing for
Device functionality
Package integrity and strength
Residue dissipation rates
Impact of re-sterilization
15
COMMISSIONING
Equipment specifications/diagram
Calibration records
Profiles for
Preconditioning (temp. and RH)
Aeration rooms (temp.)
Empty chamber temperature distribution
16
PQ - PHYSICAL
Profiles within loaded preconditioning and
aeration areas
Loaded chamber temperature distribution
studies
Diagrams showing load configuration,
thermocouple and BI placement
17
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
18
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
19
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
20
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
21
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)
22
BIOBURDEN TESTING
Test 10 samples randomly selected
Determine recovery factor – validation
If bioburden >100, comparative resistance
study required
If bioburden <100, you are OK
23
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
24
VALIDATION CYCLES
Fractional cycles
Half cycles
Full cycles
25
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
26
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
27
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
28
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
29
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
30
ACCEPTANCE CRITERIA (cont.)
Temperature sensors <10°C
Humidity sensors <30%
EO residual
Product functionality
Package integrity
LAL
31
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
32
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
33
REFERENCES
AAMI/ISO 11135-01 4ed. 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
34
THANK YOU
Q&A
