RADIATION STERILIZATION VALIDATION (PowerPoint) by mikesanye

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									VALIDATING HEAT STERILIZATION


              Pacific BioLabs Inc.
                (510) 964-9000
           info@PacificBioLabs.com
HEAT STERILIZATION METHODS

 Moist Heat (Steam)
    Heat derived under conditions of saturated water
 Dry Heat
    Heated filtered air distributed throughout an oven
     by convection or radiation




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HEAT STERILIZATION - HOW IT WORKS?

   Inactivation of a single molecule
   Disruption of a single reaction
   Protein denaturation
   Destruction of enzymes
   Destruction of non-covalent bonds




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                 D-VALUE

 Time required to reduce the population of an
  organism by 90%
  (1 Log) at a given temperature.




                                                 4
         STEAM vs. DRY HEAT

 Bacillus subtilis D-Values
    Steam    @ 121°C      ~ 0.3 min
    Dry Heat @ 120°C      ~ 240 min
              @ 140°C      ~ 2.4 min

    Steam is approximately 100-1000 times more
     effective than dry heat.




                                                  5
                DRY HEAT

 Parameters
   170 °C for 1 hour
   140 °C for 3 hours
 Advantages
   Large volume, ease of use, useful for powders
    and oils
 Disadvantages
   Temperature too high, long cycles, not useful
    for rubber, plastics, limited packaging



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WHY USE STEAM STERILIZATION

 Efficiency of heat transfer by steam
 Efficacy of the moist heat sterilization process
    Sterilizing agents
       – Steam
       – Heat Transfer




                                                     7
      CRITICAL PARAMETERS

 Moisture
 Temperature
 Contact with surfaces
 Air elimination (if using saturated steam)
 Time
 Pressure/vacuum conditions




                                               8
        STEAM STERILIZATION
          TEMPERATURES
 Can be accomplished between 50°C - 145°C
 Industrial sterilization is typically done at 121°C
 Hospitals often use cycles between 132-145°C
    Flash cycles




                                                        9
      CONTACT WITH SURFACE

 Packaging permeable to moist heat
 Items designed to allow contact
 Items must be placed in package to allow air
  removal
 Chamber load must not be overcrowded




                                                 10
  AIR IN STEAM STERILIZATION

 Reduces the efficiency of heat transfer from
  steam to the load
 Can prevent moist heat effects to impart
  microbial lethality
 Must be removed or mixed with saturated
  steam




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      STERILIZATION CYCLES

 Gravity Displacement
   Steam enters the sterilizer and displaces
    residual air through an open vent
 Vacuum Air Removal
    Air is removed with a mechanical pump
     prior to dwell time




                                                12
SATURATION TEMPERATURES
AND PRESSURES FOR STEAM
       °C   psig
      110    6.1
      115    9.9
      120   14.1
      121   15.2
      125   19.0
      130   24.5
      135   30.7




                          13
        AIR/STEAM MIXTURES

 Air/steam mixtures protect integrity of
  package/product
    Overpressure is introduced to keep
     package intact
    If pressure is released too quickly, seals
     may be affected
    For liquid devices, pressure must be
     released slowly




                                                  14
PRODUCT DESIGN CONSIDERATIONS

  Driven by performance requirement
  Is the material tolerant to
   heat/moisture/pressure
  Device shape
  Re-Sterilization




                                       15
 PACKAGING CONSIDERATIONS

 Must allow sterilant in and be breathable
  during cycle
 If steam comes from product, closure may be
  absolute to the outside
 Must allow efficient heat transfer
 Must remain aesthetically acceptable
 Seals must withstand temp, pressure, and
  moisture ranges during cycle



                                                16
LOAD CONTENT CONSIDERATIONS

 Configuration of production load must be
  specified
 Heating characteristics of chamber and load
  must be determined
 For liquids, fill volumes and location in load
  are critical




                                                   17
       MICROBIOLOGY OF
    MOIST HEAT STERILIZATION
 Most vegetative forms are susceptible to ~80°C
 Bacterial spores are more resistant
    Geobacillus stearothermophilus requires a
     temperature of ~ 121°C
 Microbial lethality follows first order kinetics




                                                     18
 MICROBIOLOGICAL MONITORS

 Biological Indicators (BIs)
    Liquid suspensions
    Lyophilized cultures
    Attached to paper, thread or metal carriers
 Performance characteristics required by ISO
  and USP
    Microbial characterization
    Population
    Resistance testing (D-value and Z-value)


                                                   19
                  BIs (cont.)

 Spore population of BIs must be equivalent to 10 6
 Moist heat -G. stearothermophilus
 Dry heat- Bacillus atrophaeus
 Must be placed at most difficult to sterilize location
   Process Challenge Device (PCD) may be used




                                                           20
        STERILIZATION MODELS

 Overkill
 Combined BI/Bioburden
 Absolute Bioburden




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      CONCEPT OF F-VALUES

 Since microorganisms start to die as
  temperature gradually increases, cycles can
  be designed to take advantage of
  CUMULATIVE moist heat exposure
  throughout the ENTIRE cycle




                                                22
  CONCEPT OF F-VALUES (cont.)

 Bioburden is known to be less resistant than BI
 BIs D and Z values must be known
 Fo
    Equivalent minutes at 121°C
 Very useful for heat sensitive products or large
  volume containers




                                                     23
  CONCEPT OF F-VALUES (cont.)

 Example
    With a D value of 1 and a Z value of 10, it will
     take 12 minutes at 121°C to produce an SAL
     of 10-6 starting with a population of 106
    At 114°C, it would take 60 min




                                                        24
     VALIDATION OBJECTIVES

 Demonstrate that:
    The sterilization process will consistently
     achieve sterility
    The sterilization process will not have an
     adverse impact on the device or its
     packaging




                                                   25
  VALIDATION REQUIREMENTS

 IQ
 OQ
 PQ
 Documentation




                            26
                        IQ

 Utilities
    Water, electrical, steam, air
 Construction and design issues
    Piping
    Steam distribution system
    Control and recording technology
    Building adequacy




                                        27
                     OQ

 Controls and measurement equipment is
  calibrated
 Adequate function of vacuum if present
 Reproducible heating throughout the chamber
  must be demonstrated
    3 empty chamber cycles




                                                28
                      PQ

 Done with actual product and load configuration
    Maximum load
    Minimum load
 Temperature mapping
 BI Testing




                                                    29
                   PQ (cont.)

 How many BIs?
    Sufficient to indicate reproducibility
 How many cycles?
    At least 3 replicate half cycles
     (microbiological validation)
    At least 3 replicate full cycles (product and
     package performance testing)




                                                     30
  ASSESS IMPACT OF PROCESS

 Test performance of product and package
  following sterilization:
    Package integrity and seal strength
    Device meets products specifications for
      functionality




                                                31
      VALIDATION PROTOCOL

 Purpose and objectives
 Equipment
 Tests to be performed and rationale
 Detailed test methods
 Acceptance criteria
 Approvals
 Effective date
 Supporting documentation

                                        32
        VALIDATION REPORT

 Documentation of:
    Assessments of equipment
    Results of process testing
    Deviations and rationale for determining
     impact on the validation study
    Meeting of acceptance criteria
    The establishment of processing parameters




                                                  33
         PRODUCT RELEASE

 Goal for production runs should be parametric
  release
    A sterility release procedure based upon
     effective control, monitoring and
     documentation of a validated sterilization
     process cycle in lieu of release based
     upon end product sterility testing




                                                  34
     PRODUCT RELEASE (cont.)

 Examine all data
    Temperature and time
    BIs if used
    Sterility test of product if used
      – One more piece of evidence
      – Can be based on USP




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                 REFERENCES

 AAMI TIR 13:1997, Principles of industrial moist heat
  sterilization
 ISO 11138-1 Sterilization of health care products -
  Biological indicators- Part 1: General Requirements
 Steam Sterilization a Practitioner’s Guide. 2003. Edited
  by Moldenhauer, J. PDA, Bethesda MD, DHI
 USP 2005 <1211> Sterilization and Sterility Assurance
  of Compendial Articles
 ANSI/AAMI ST79:2006 Comprehensive guide to steam
  sterilization and sterility assurance in health care
  facilities



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THANK YOU

  Q&A

								
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