Process

WHAT IS STERILIZATION?

Sterile: Free from any living organisms.

Sterilization: Process of killing or removing microorganisms from a product to insure that it is sterile.

EO ADVANTAGES

  • Highly effective against most microbes
  • Highly diffusive
  • Compatible with a wide variety of materials in devices and packaging

EO DISADVANTAGES

  • Complex process
  • Longer turn-around times
    • BI Testing
    • Residual dissipation
  • Safety concerns
    • Flammable
    • Explosive
  • OSHA concerns
    • Carcinogen
  • EPA concerns
    • Emissions

USERS OF ETHYLENE OXIDE

  • Anyone who supplies a product on which the presence of microorganisms could present a health risk.
  • Manufacturers of any product that enters the body, except by ingestion:
    • Medical Device Manufacturers
    • Pharmaceutical Manufacturers (Both human & veterinary)
  • Hospitals, Dentists, other health care facilities
  • Some specialty food product manufacturers

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

DECISIVE PROCESS PARAMETERS

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

DEEP VACUUM CYCLE

SHALLOW VACUUM CYCLE

FACTORS AFFECTING CYCLE SUCCESS

  • Bioburden
  • Product/package properties
  • Loading configuration
  • Cycle parameters

DETERMINE THE STANDARD

  • AMI/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

EO VALIDATION OVERVIEW

  • Process development
  • Product compatibility
  • Commissioning
  • PQ – Physical
  • PQ – Microbiological
  • Certification
  • Revalidation

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

RELEASE MECHANISMS

  • Documentation showing that processing specification are met
  • Successful results of tests
    • Sterility of BI
    • EO residues
    • Packaging
    • Pyrogens

PARAMETRIC RELEASE

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

PRODUCT COMPATIBILITY

  • Post sterilization testing for
    • Device functionality
    • Package integrity and strength
    • Residue dissipation rates
    • Impact of re-sterilization

COMMISSIONING

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

PQ – PHYSICAL

  • Profiles within loaded preconditioning and aeration areas
  • Loaded chamber temperature distribution studies
  • DiAhmedabadms showing load configuration, thermocouple and BI placement

PQ – MICROBIOLOGICAL

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

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

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

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

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)

BIOBURDEN TESTING

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

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

VALIDATION CYCLES

  • Fractional cycles
  • Half cycles
  • Full cycles

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

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

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

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

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

ANSI/AAMI/ISO Standards Ethylene Oxide Sterilization

  • Medical Devices – Validation and routine control of EO sterilization (ANSI/AAMI/ISO 11135: 1994)
  • Contract Sterilization for EO (AAMI TIR 14:1997)
  • Process development and performance qualification for ethylene oxide sterilization -microbiological aspects (AAMI TIR 16:2000)
  • Parametric release for EO sterilization (TIR 20)
  • Biological Evaluation of Medical Devices-Part 7: EO sterilization residuals (10993-7)

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