1

Sterilization/Depyrogenation Validation: Non-Product Introduction This procedure provides guidance for validating sterilization and depyrogenation of equipment, and containers and closures with direct or potential contact with sterile medical devices, sterile drug products, or sterile active pharmaceutical ingredients (API). 1. Preventive Maintenance (PM) Measures should include, and not be limited to,

the following: For Steam • Calibrate instruments and elements (I/Es); • Check operation of vacuum pumps; • Clean chamber, steam traps and drains; • Perform leak test of the chamber; • Replace and integrity test vent filter; • Verify* the operation of safety devices; and • Check door seals and gaskets for deterioration. For Dry Heat Ovens and Tunnels • Calibrate I/Es; • Check operation of electric heating elements; • Operation of pressure differential monitoring equipment and alarms; • Clean chamber, belts, baffles, and dampers; • Verify fan and belt speed; • Replace belt when required; • Integrity test HEPA Filters; and • Check door seals for deterioration.

For EtO • Calibrate I/Es; • Check operation of vacuum pumps; � Replace vent filter; • Verify integrity of heat exchangers; • Clean chamber; • Perform leak test of the chamber; • Check operation of exhaust gas scrubbers; and • Check door seals and gaskets for deterioration.

2. Critical Process Parameters (e.g., temperature, exposure time) for each type of

Title: Sterilization/Depyrogenation Validation: Non-Product Guidance Number: 117 Prepared by: Date: Supersedes:

Checked by: Date: Date Issued:

Approved by: Date: Review Date:

3

9. I Lots Demonstrating Kill Times in excess of what is required to demonstrate

the sterilization end-point for the process being evaluated should not be used. 10. All BIs Used in Validation Studies should be accounted for, before and after

processing. 11. For Steam Sterilization Processes, BIs are available in four (4) forms:

• Spores added to a carrier (e.g., a disk or strip of filter paper, glass, plastic or other material) and packaged to maintain the integrity and viability of the inoculated carrier (preferred and most commonly used in non-product sterilization validation);

• Self-contained packaged indicator that includes the culture medium separated from the BI (e.g., a paper strip surrounding a sealed ampoule containing culture medium that is activated after exposure);

• Self-contained packaged indicator that includes the spores suspended in the culture medium in a sealed ampoule (most often used for submersion in liquids); and

• Spore suspension added to representative units of the product, simulated product, or onto non-product surfaces (e.g., closures). Such suspensions are most often used for product terminal sterilization validation.

12. Steam Sterilization Cycle Development should include the following:

• Runs performed using BIs (e.g., Geobacillus stearothermophilus, formerly referred to as Bacillus stearothermophilus) which have a predetermined spore population (e.g., 105 to 106), D-value, and kill time; and

• Incubation of BIs at 55oC-60oC withno growthafter seven(7) days or at the temperature and time periods recommended by the BI supplier.

13. Steam Sterilization OQ/PQ Studies should be performed and include, and not

be limited to, the following: • A minimum of three (3) temperature distribution runs on an empty

chamber to confirm heating uniformity and identify the slowest-to-heat zone;

• Heat penetration runs on each different load configuration to identify cold spots, the effect of loading on thermal input, and the worst case load configuration;

• A minimum of three (3) consecutive, successful runs on the worst case load configuration using minimum cycle parameters and BIs and meeting all validation acceptance criteria; and

• One run with the minimum load configuration. 14. For DH Sterilization Processes, BIs are available in two forms:

• Spores added to a carrier (e.g., paper strips); and • Spores added to representative units (e.g., inoculated stainless steel

coupons). Where the process has been shown to depyrogenate by inactivation of three (3) logs of endotoxin, it is not necessary to challenge with bacterial spores.