Transcript RADIATION STERILIZATION VALIDATION

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