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Sterilized, Validated, Documented and
Pyrogen Tested WipersOlivier Gautier
Agenda
· Sterile Wiper Benefits
· Sterile Wiper Applications
· Sterile Products
· Sterilization Process
· Sterility Validation Process and Auditing
· Documentation
Sterile Wiper Benefits
· Integrity of cleanroom is maintained
· Low levels of releasable particles and fibers
· Bags are solvent-safe for wipedown
· Terminally sterilized by gamma irradiation
· Sterility validated and audited
· Each inner bag is lot and expiration date coded
· Irradiation indicator dot on each case
· Certificates of Irradiation and Compliance are attached to each case
· Validated shelf life (3 years)
Sterile Wiper Applications
· Cleaning aseptic environments
· Floor, walls and ceiling
· Cleaning equipment and environmental surfaces in sterile environment (Class A/B)
· Process equipment, isolators, RABS
· Applying cleaning solutions and disinfectants
· Spill control
· Final wipedown after disinfection
· Wipedown of articles in pass-through
· Wiping gloved hands
Sterile Products
·Dry wipers
·Pre-wetted wipers
·Mop wipers and covers
·Swabs
· IPA / Ethanol
Sterilization Process
· Gamma Irradiation
· Electron Beam
· Steam Autoclaving
· VHP
Sterilization Process
Sterile & Validated Wipers
· Manufactured in cleanroom environment
· Controlled bioburden
· Double or triple bagged in cleanroom packaging
· Allows easy entry into aseptic environment
· Package integrity tested
· Validated
· Fully documented in validation package
Autoclaved Wipers
· Re-bagging of product is needed
· Environment control?
· Cleanroom bags quality?
· Handling issues?
· Potential contamination?
· Extra time needed
· Autoclave cycle to validate
· QC Testing
· Microbiological testing
· Documentation to establish
Sterilization Process
Gamma Irradiation:
·More penetrating power than E-Beam
·Relatively easy process to validate
·Leaves no residues from treatment
·Compatible with many materials and solutions
·Gamma irradiation shows endotoxin level reduction to a greater extend than E-Beam irradiation
· Bacterial endotoxins or pyrogens are fever-causing materials from the outer cell membranes of Gram-negative bacteria
Sterilization Process
Dose vs. Depth Comparison of E-Beam and Gamma Sterilization
Reid. B.D., “Gamma Processing Technology: An Alternative Technology for Terminal Sterilization of Parenterals,” PDA Journal of Pharmaceutical Science & Technology, Vol. 49, No. 2, 1995, pp 83-89
Sterilization Process
Effects of Gamma Rays and Accelerated Electrons on Endotoxins (e. Colli on polystyrene)
Guyomard, S., V. Goury, J. Laizier and J.C. Darbord, “Defining of the Pyrogenic Assurance Level (PAL) or Irradiated Medical Devices, “International Journal of Pharmaceuticals, Vol. 40, 1987, pp 173-174
Sterility Validation Process and Auditing
· Follow AAMI Guidelines (Association for the Advancement of Medical Instrumentation)
· To assure a 10-6 sterility assurance level (SAL)
· Validation
· Determine bioburden
· Determine gamma irradiation dose and subprocess dose
· Test sterility after irradiating at subprocess levels
· Quarterly auditing
· Determine bioburden
· Test sterility after irradiating at subprocess levels
Sterility Validation Process and Auditing
Validation process
·Bioburden – Determination (Step 1)
· 10 wipers of 3 different lots are tested to quantify the number of CFU (Colony Forming Units) per wiper
· Recovery – Determination (Step 2)
· Repeated extractions of 3 wipers to determine the total CFU
· The bioburden data are corrected for this extraction efficiency
Sterility Validation Process and Auditing
Validation process
·Dose (Step 3)
· Gamma irradiation from a Cobal-60 source
· Dose is chosen to predict allowing less than a one in a million probability of any surviving CFU on the item
· Sterility Assurance Level (SAL) = 1 ppm
Sterility Validation Process and Auditing
Validation process
·Sub-Process Dose Validation (Step 4)
· This validation is done by irradiating with an appropriately lower dose, such that there is a 1/100 probability than any organisms can survive on an item, then testing 100 wipers so irradiated for sterility.
· AAMI indicates that if two or fewer items of the 100 are non-sterile, the dose is validated. Routinely, all 100 are sterile.
Sterility Validation Process and Auditing
Validation process
·Irradiation (Step 5)
· Monitored with dosimeters
· For every irradiated lot a Certificate of Processing (CoI)
Sterility Validation Process and Auditing
Validation process
·Documentation (Step 6)
· Certificate of Irradiation or Processing (CoI)
· Certificate of Compliance (CoC)
· Certificate of Analysis (CoA)
· Supplier audits (Step 7)
Sterility Validation Process and Auditing
· Audit Process Flow
Test Results Recorded
Bioburden Testing
Test Results Recorded
Sterility Testing
Sub-dose Irrad iation
Product Released for Sale
Certificate of Processing
Sterigenics Irradation
Product ManufacturedNon-irrad iated
Sterility Validation Process and Auditing
Pyrogens or Endotoxins (Step 8)·Toxins from killed gram-negative bacteria·Allowable limit of endotoxins in human and animal parenteral drugs, biological and medical devices are established by the FDA
· Match USP 23 supplement 1 <161> (United State Pharmacopeia)
· Limits in parenteral: less than 20 endotoxin units per device (< 20 EU/device)
· Removing is extremely difficult prevention (bioburden)
· Measuring of endotoxins with LAL-testing
Documentation
Full Validated and Documented Package (Step 9) ·Product Technical Data Sheet·TechNote·Packaging Integrity Test·All Certificates (CoI, CoC, CoA)·Sterility Validation Test and Control
· Bioburden test on wiper materials (CFU)· Sterility Assurance Test· Bacterial Endotoxins or Pyrogens
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