VALIDATING HEAT STERILIZATION

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VALIDATING HEAT STERILIZATION

• Pacific BioLabs Inc.
• [phone]
• info_at_PacificBioLabs.com

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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.

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STEAM vs. DRY HEAT

• Bacillus subtilis D-Values
• Steam _at_ 121C 0.3 min
• Dry Heat _at_ 120C 240 min
• _at_ 140C 2.4 min
• Steam is approximately 100-1000 times more
  effective than dry heat.

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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

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CRITICAL PARAMETERS

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

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STEAM STERILIZATIONTEMPERATURES

• Can be accomplished between 50C - 145C
• Industrial sterilization is typically done at
  121C
• Hospitals often use cycles between 132-145C
• Flash cycles

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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

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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

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SATURATION TEMPERATURESAND PRESSURES FOR STEAM
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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

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PRODUCT DESIGN CONSIDERATIONS

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

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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

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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

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MICROBIOLOGY OFMOIST HEAT STERILIZATION

• Most vegetative forms are susceptible to 80C
• Bacterial spores are more resistant
• Geobacillus stearothermophilus requires a
  temperature of 121C
• Microbial lethality follows first order kinetics

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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)

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BIs (cont.)

• Spore population of BIs must be equivalent to 106
• Moist heat -G. stearothermophilus
• Dry heat- Bacillus atrophaeus
• Must be placed at most difficult to sterilize
  location
• Process Challenge Device (PCD) may be used

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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

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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 121C
• Very useful for heat sensitive products or large
  volume containers

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CONCEPT OF F-VALUES (cont.)

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

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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

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VALIDATION REQUIREMENTS

• IQ
• OQ
• PQ
• Documentation

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IQ

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

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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

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PQ

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

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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)

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ASSESS IMPACT OF PROCESS

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

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VALIDATION PROTOCOL

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

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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

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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

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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 131997, Principles of industrial moist
  heat sterilization
• ISO 11138-1 Sterilization of health care products
  - Biological indicators- Part 1 General
  Requirements
• Steam Sterilization a Practitioners Guide. 2003.
  Edited by Moldenhauer, J. PDA, Bethesda MD, DHI
• USP 2005 lt1211gt Sterilization and Sterility
  Assurance of Compendial Articles
• ANSI/AAMI ST792006 Comprehensive guide to steam
  sterilization and sterility assurance in health
  care facilities

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THANK YOU

• Q A