1. MEDICAL DEVICE STERILIZATION
Pacific BioLabs Inc.
(510)

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)

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

6. STERILIZATION METHODS
Radiation
Ethylene Oxide
Moist Heat
Rapid
No residues
Good for
convoluted
shapes
Compatibility
with many
materials
Good for heat
sensitive
products
Economical

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 Chemical – Alkylates proteins and DNA
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 MICROBIOLOGIST VIEWS BACTERIA

11. HOW MANUFACTURING AND QA VIEW BACTERIA

12. EO PROS & CONS Pros Cons 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 Cons
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 Cons 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 Cons 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 (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