1. Sterilized, Validated, Documented and Pyrogen Tested Wipers
Olivier Gautier

2. Agenda Sterile Wiper Benefits Sterile Wiper Applications
Sterile Products
Sterilization Process
Sterility Validation Process and Auditing
Documentation

3. 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)

4. 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

5. Sterile Products Dry wipers Pre-wetted wipers Mop wipers and covers
Swabs
IPA / Ethanol

6. Sterilization Process
Gamma Irradiation
Electron Beam
Steam Autoclaving
VHP

7. 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

8. 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

9. 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

10. 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

11. 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

12. Sterility Validation Process and Auditing
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

13. Sterility Validation Process and Auditing
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

14. Sterility Validation Process and Auditing
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.

15. Sterility Validation Process and Auditing
Irradiation (Step 5)
Monitored with dosimeters
For every irradiated lot a Certificate of Processing (CoI)

16. Sterility Validation Process and Auditing
Documentation (Step 6)
Certificate of Irradiation or Processing (CoI)
Certificate of Compliance (CoC)
Certificate of Analysis (CoA)
Supplier audits (Step 7)

17. Sterility Validation Process and Auditing
Audit Process Flow

18. 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

19. 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