ETHYLENE OXIDESTERILIZATION VALIDATION

Pacific BioLabs Inc.(510) 964-9000

info@PacificBioLabs.com

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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

THANK YOU

Q & A