RADIATION STERILIZATION VALIDATION

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RADIATION STERILIZATION VALIDATION

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

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TYPES OF RADIATION

• Alpha
• 2 protons and 2 neutrons, positively charged,
  stopped by a sheet of paper
• Beta
• Fast moving electrons, more penetrating than
  alpha, stopped by book or human tissue
• Gamma
• Very penetrating electromagnetic radiation, pass
  through human body, stopped by concrete wall
• X-Ray
• Form of electromagnetic radiation produced by
  artificial means

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STERILIZATION PROCESS VALIDATION

• Product qualification
• Installation qualification
• Process qualification
• Administrative procedure to review and approve
  documentation
• Maintenance of validation

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PRODUCT QUALIFICATION

• Effect of radiation on product materials and
  packaging
• Quality, safety and performance of the product
  throughout its shelf life
• Testing may include
• Strength
• Clarity and color
• Biocompatibility
• Package integrity

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RADIATION EFFECTS ON MATERIALS

• Brittle
• Color
• Odor
• Stiffness
• Softens
• Toxicity
• Chemical inertness
• Melt temperature

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INSTALLATION QUALIFICATION

• Equipment documentation
• Equipment testing
• Equipment calibration
• Irradiator dose mapping

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PROCESS QUALIFICATION

• Determination of product loading pattern
• Product dose mapping

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ROUTINE PROCESS CONTROL

• Process specification
• Product handling
• Routine preventive maintenance
• Product irradiation
• Process documentation
• Sterilization acceptance

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RADIATION VALIDATION APPROACHES

• Sterilization dose is selected using the
  bioburden information
• AAMI Method 1 and 2
• Appropriateness of 15-30 kGy can be substantiated
• VDmax Method

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DOSE DETERMINATION METHODS

• ANSI/AAMI/ISO 11137-2 -2006
• Method 1 - dose is determined based on product
  bioburden
• Method 2 - dosed is determined by incremental
  dose experiments
• VDmax Method substantiation of 15 and 25 kGy
  dose
• AAMI TIR332005
• VDmax Method substantiation of 15 - 35 kGy dose

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ANSI/AAMI/ISO 11137-22006 METHOD 1

• Protocol
• Bioburden Validation
• Bioburden
• Verification Dose Calculation
• Verification Dose Experiment
• Irradiation
• Bacteriostasis and fungistasis test
• Sterility test
• Summary Report

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METHOD 1 (cont.)

• Bioburden Validation
• 3 to 5 units
• Exhaustive recovery or inoculated product
• Calculate correction factor for recovery
  efficiency
• Bioburden Test
• 10 units from 3 different batches that have gone
  through every step of production except
  sterilization

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METHOD 1 (cont.)

• Verification Dose Calculation
• Determine the individual batch and overall
  average bioburden
• If any single batch average is more than twice
  the overall average that particular batch average
  is used
• Use extraction efficiency factor to calculate the
  theoretical bioburden
• Set the verification dose (kGy) using an SAL of
  10-2 on Table 5

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METHOD 1 (cont.)

• Verification Dose Experiment
• Product irradiation of 100 units at the
  verification dose 10
• Sterility test of 100 units using SCDM incubating
  at 28-32ºC for 14 days
• Interpretation
• lt2 non-sterile validation passed and can
  release product at 10-6 kGy
• gt3 non-sterile validation failed

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METHOD 1 AUDIT

• Must be conducted every quarter for continued
  release of product
• Bioburden 10 non-sterile products
• Review of environmental controls
• Sterility test of 100 units sterilized at 10-2
• Interpretation
• lt2 non-sterile passed
• 3 or 4 non-sterile dose should be augmented
• 5 or 6 non-sterile w/ bioburden increase -
  augment
• 5 or 6 non-sterile w/out bioburden increase
  -revalidate
• 7 or more non-sterile - revalidate

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AAMI TIR332005 VDMAX METHOD

• Sterilization of health care products Radiation
  sterilization Substantiation of 15-35 kGy as a
  sterilization dose Method VDmax
• Bioburden must be lt1,000 CFU/device

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AAMI/ISO TIR No. 158441998

• Sterilization of health care products
  Radiation sterilization- Selection of a
  sterilization dose for a single production batch
• Very similar to Method 1
• Bioburden of 10 devices instead of 30

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VDMAX METHOD (cont.)

• Protocol
• Bioburden Validation
• Bioburden
• Verification Dose (VDmax) Calculation
• Verification Dose Experiment
• Irradiation
• Bacteriostasis and fungistasis test
• Sterility test
• Summary Report

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VDMAX METHOD (cont.)

• Verification Dose Experiment
• Product irradiation of 10 units at the
  verification dose 10
• Sterility test of 10 units using SCDM incubating
  at 28-32ºC for 14 days
• Interpretation
• lt1 non-sterile validation passed and can
  release product at selected kGy
• gt2 non-sterile confirmatory test
• gt3 non-sterile validation failed

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VDMAX METHOD (cont.)

• Confirmatory Verification Dose Experiment
• 10 devices irradiated at confirmatory dose
• Confirmatory dose verification dose
• All sterile selected dose (kGy) substantiated
• gt1 non-sterile validation failed

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VDMAX METHOD AUDIT

• Must be conducted every quarter for continued
  release of product
• Bioburden 10 non-sterile products
• Review of environmental controls
• Sterility test of 10 units sterilized at
  verification dose
• Interpretation
• lt1 non-sterile passed
• 2 non-sterile confirmatory test
• gt3, lt6 non-sterile augment dose and revalidate
• 7 or more non-sterile - revalidate

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SINGLE PRODUCTION BATCH VDMAX

• Selected dose (kGy) can be validated as a
  sterilization dose for a single batch
• Method is limited to a single production batch
  and no provisions are given for audits or
  augmentation
• Testing difference bioburden of 10 devices
  instead of 30

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SAMPLE ITEM PORTION (SIP)

• Defined portion of health care product that is
  tested
• Should be as large a portion of product that is
  convenient to handle during testing
• Adequacy must be demonstrated
• Bioburden present in gt85 of samples, or
• Sterility testing of 20 units must result in 17
  positives
• Verification Dose SIP1 kGy (log SIP x
  reduction factor)

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PRODUCT FAMILIES ANDFREQUENCY OF AUDITS

• ANSI/AAMI/ISO TIR 158432000
• Sterilization of health care products- Radiation
  sterilization - Product families, sampling plans
  for verification dose experiments and
  sterilization dose audits, and frequency of
  sterilization dose audits

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PRODUCT FAMILIES

• Documented criteria for establishing a product
  family
• Raw materials
• Components
• Product design
• Manufacturing process, equipment, environment,
  location

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A FAMILY OF PRODUCTS SHALL BE REPRESENTED BY

• The master product
• An equivalent product
• A simulated product
• Selection must be based on
• and type of organism
• Size of product and number of components
• Complexity of product
• Degree of manufacturing automation
• Manufacturing environment

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SAMPLE SIZES

• TIR 15843 offers provision for reducing the
  sample size for verification dose experiments and
  dose audits
• Example Method 1
• 52 units instead of 100 ? 0() OK
• 70 units instead of 100 ? 1() OK

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FREQUENCY OF AUDITSCONDITIONS FOR REDUCTION

• From a 3-month to 6-month
• 4 successful consecutive quarterly audits
• Bioburden characterization
• Controlled manufacturing environment
• From a 6-month to 12-month
• 2 successful consecutive biannual audits
• Bioburden characterization
• Controlled manufacturing environment

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REFERENCES

• ANSI/AAMI/ISO TIR 158432000, Sterilization of
  health care products-Radiation sterilization-Produ
  ct families and sampling plans for verification
  dose experiments and sterilization dose audits,
  and frequency of sterilization dose audits
• AAMI TIR 302005, Sterilization of health care
  products-Radiation - Substantiation of a selected
  sterilization dose-Method VDmax
• ANSI/AAMI/ISO 11737-1- 2006, Sterilization of
  health care products-Microbiological
  methods-Part1 Determination of the population of
  microorganisms on products
• AAMI/ISO 11737-2 -1998, Sterilization of medical
  devices-Microbiological methods-Part 2 Tests of
  sterility performed in the validation of a
  sterilization process

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REFERENCES (cont.)

• AAMI/ISO TIR No. 158441998, Sterilization of
  health care products-Radiation sterilization-Selec
  tion of a sterilization dose for a single
  production batch
• AAMI TIR No. 17 1997, Radiation
  Sterilization-Material Qualification
• ANSI/AAMI/ISO 11137-12006, Sterilization of
  health care products-Radiation-Part 1
  Requirements for development, validation, and
  routine control of a sterilization process for
  medical devices
• ANSI/AAMI/ISO 11137-22006, Sterilization of
  health care products-Radiation-Part 2
  Establishing the sterilization dosE

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THANK YOU

• Q A