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

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

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

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

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

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

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

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

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

HOW A MICROBIOLOGIST VIEWS BACTERIA

HOW MANUFACTURING AND QA VIEW BACTERIA

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

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

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

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

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

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

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

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

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)

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

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

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

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

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

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

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

THANK YOU Q & A