ETHYLENE OXIDE STERILIZATION VALIDATION by rbc14327

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									    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




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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




                    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



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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”




                                            14
     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

                                                 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



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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

								
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