Sterilized, Validated, Documented and Pyrogen Tested Wipers Olivier 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

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

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

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.

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

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)

Sterility Validation Process and Auditing Audit Process Flow

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