MEDICAL DEVICE STERILIZATION

1. MEDICAL DEVICE STERILIZATION Pacific BioLabs Inc. (510) 964-9000 info@PacificBioLabs.com

2. OUTLINE – MORNING SESSION • 8:30 Introduction • 8:45 General Principles of Sterilization & Validation • 9:15 Contract Sterilizers and Testing Laboratories • 10:15 Break • 10:30 Radiation Sterilization Validation • 11:45 Validating Heat Sterilization • 12:30 Lunch

3. OUTLINE – AFTERNOON SESSION • 1:30 Ethylene Oxide Sterilization Validation • 3:00 Break • 3:15 Monitoring Controlled Environments • 4:15 Class Exercise, Discussion, Q&A

4. GENERAL PRINCIPLES OF STERILIZATION AND VALIDATION Pacific BioLabs Inc. (510) 964-9000 info@PacificBioLabs.com

5. STERILIZATION METHODS • Moist Heat • Radiation (Gamma and E-beam) • Ethylene Oxide (EO) • Hydrogen Peroxide • Gas Plasma

6. STERILIZATION METHODS

7. PRODUCT DESIGN CONSIDERATIONS • Driven by performance requirement • Is the material tolerant to radiation, heat, moisture, EO? • Device shape • Re-Sterilization

8. STERILIZATION MARKET • Ethylene Oxide (EO) 49% • Gamma Radiation 44% • E-beam Radiation 7%

9. HOW DOES IT WORK? • Purpose • To kill bugs while keeping the devices functional • Chemical – Alkylates proteins and DNA • Radiation – DNA degraded by ionization • Heat – Oxidizes and denatures enzymes

10. HOW A MICROBIOLOGISTVIEWS BACTERIA

11. HOW MANUFACTURING ANDQA VIEW BACTERIA

12. EO PROS & CONS • Pros • Most materials compatible • Relatively low temperature process • Most packaging materials OK • Relatively low cost • Cons • Penetration sometimes difficult • Residuals • Batch process • Long process and release time

13. GAMMA PROS & CONS • Pros • Well characterized parametric (fast) release • Penetrates well • Most materials OK • Cons • More expensive than EO • Not in-house process • PTFE and acetal difficult • Yellowing and embrittlement of some polymers

14. E-BEAM PROS & CONS • Pros • Same as gamma except kinder to materials • Most easily scalable • Turnaround time BEST • Cons • Lower penetration and density limited • Not in house process for small companies • Some materials remain unsuitable

15. STEAM PROS & CONS • Pros • More tolerant material available • More packaging choices • Relatively inexpensive • Often used in-house • Cons • Batch process • Few polymer-based devices work • Packaging aesthetics not great • Some maintenance costs

16. PACKAGING CONSIDERATIONS-RADIATION PROCESSES • Materials compatible with dose needed for sterilization without embrittlement or other physical problem over the life of the product • Must remain aesthetically acceptable. • Appearance • Feel • Odor

17. PACKAGING CONSIDERATIONS-MOIST HEAT PROCESSES • Must allow sterilant in and be breathable during cycle • Must remain aesthetically acceptable • Must allow efficient heat transfer • Seals must withstand temp, pressure, and moisture ranges during cycle

18. PACKAGING CONSIDERATIONS-EO PROCESSES • Must allow sterilant in and be breathable during cycle • Must remain aesthetically acceptable • Must allow gas elution during aeration • Seals must withstand temperature, pressure, and moisture ranges during cycle

19. DOCUMENT! DOCUMENT! DOCUMENT! • Decisions and rationale for selected sterilization process • Procedures, rationales, and results of post-exposure testing

20. WHY VALIDATE? • Quality System regulation: “Where the results of a process cannot be fully verified by subsequent inspection and test, the process shall be validated with a high degree of assurance and approved according to established procedures” • 21 CFR 820.75 (a)

21. VALIDATION OBJECTIVES • Demonstrate that: • The sterilization process will consistently achieve sterility • The sterilization process will not have an adverse impact on the device or its packaging

22. STERILITY • Definition: • State of being free from viable organisms • In practice, no such absolute statement regarding the absence of microorganisms can be proven. Therefore a sterility assurance level (SAL) is used to define the objective in sterilization processing

23. LABELING AS STERILE • Testing for sterility vs. SAL • Sterility Assurance Level • Probability of a viable organism being present on a product unit after sterilization • FDA SAL 10-6 for invasive devices • FDA SAL 10-3 for non-invasive devices • EC SAL 10-6 for all

24. BASIC VALIDATION CONCEPTS • Rule of three is used to demonstrate reproducibility • Worst case challenge • Resistant organism • Most difficult device • Worst case conditions • High density of load • Low end of operating conditions

25. ASSESS IMPACT OF PROCESS • Test performance of product and package following sterilization: • Package integrity and seal strength • Device meets products specifications for functionality • Assess residue dissipation

26. VALIDATION PROTOCOL • Purpose and objectives • Equipment • Tests to be performed and rationale • Detailed test methods • Acceptance criteria • Approvals • Effective date • Supporting documentation

27. VALIDATION REPORT • Documentation of: • Assessments of equipment • Results of process testing • Deviations and rationale for determining impact on the validation study • Meeting of acceptance criteria • The establishment of processing parameters

28. THANK YOU Q & A