How is Sterilization Validation Performed by the Medical Device Manufacturer? Rod Parker, Ph.D. Sr. Principal Scientist Stryker Instruments Division May 9, 2016
DISCLOSURE I am an employee of Stryker Corporation. I am involved with the manufacture of medical devices. No product preferences or names are listed or recommended by this presentation. No compensation has been received for this presentation or for travel to and from the seminar. All opinions are those of the presenter.
Topics of Interest So how do manufacturers validate their surgical equipment? o Cleaning Validations o Chemicals o Sterilization Validations
Who s driving the boat? How bad is the storm? Do you believe the Weatherman or what you see.
What does a storm have to do with sterilization of medical devices? The picture shows a front moving on the open ocean and the captain can either steer to the clear side and hope to outrun the storm, or turn into the storm and ride out the rough seas. In the market today with the current focus on healthcare acquired infections and antibiotic resistant micro-organisms, we at the a similar point in directing what is required of reprocessing medical devices. Turning to beat the storm may only work for the short run Riding it out will involve full cooperation of all crew members to insure the ship stay safe. But often.
We think we are playing the same game? But we are using the same board but have different strategies.
Definitions Sterilization Validated process used to render a product free from viable microorganisms. NOTE: In a sterilization process, the nature of microbiological inactivation is described by an exponential function. Therefore, the presence of a viable microorganism on any individual item can be expressed in terms of probability. While this probability can be reduced to a very low number, it can never be reduced to zero. See also sterility assurance level.
Definitions Validation Documented procedure for obtaining, recording, and interpreting the results required to establish that a process will consistently yield product complying with predetermined specifications. Verification (User) Documented procedures, performed in the user environment, for obtaining, recording, and interpreting the results required to establish that predetermined specifications have been met.
What Sterilization Really Looks Like. Before Gas Sterilization After Gas Sterilization
Challenge Devices Pure culture Spores Spores coated with 5% serum and hard water
The process starts with cleaning the used devices. We hear repeatedly If it is not clean, it can not be sterilized I would expand on that to state: If the level of bioburden on the device is greater than expected from the device s cleaning validation, then the ability to reach the level of sterilization expected from the sterilization validation on the device is not assured. This results in a device that is not at the sterility assurance level statistically required by the definition of sterilization. The manufacturer s process must then, first, know the expected level of bioburden resulting from the outcome of cleaning.
Initial Cleaning Evaluation Product information provided by engineer o Intended clinical application o Product design (i.e. diameter and length of lumens) o Materials of construction o Disassembly instructions o Cleaning methods Conduct product adoption or cleaning validation
Cleaning Validation Protocol (Example) Test Organisms (population of at least 1 x 10 6 ) Geobacillus stearothermophilus - spore) Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa vegetative bacteria) Inoculation Method Simulated and predetermined most challenging locations Digital Images Device prior to inoculation Device post inoculation illustrating most challenging inoculation site Automated washer configuration
Cleaning Validation Protocol (Example) Test Assays Bioburden (microbiological log reduction) Uses the known most resistant spore for the sterilization process considered Carbohydrate (tissue simulation) Used for orthopedics since bone is higher physiologically in carbohydrate than protein or hemoglobin soil markers Protein (blood simulation) Used since protein is the marker most often associated with potential of disease transmission not related to infection.
Digital Image Illustrations
Digital Image Illustrations
Digital Image Illustrations
Digital Image Illustrations
Manual Cleaning Methods Gross removal of soil Cleaning of devices with a cleaner and suitable equipment (i.e. brushes, syringes) Rinsing of devices using filter/deionized water Drying of devices with (low lint) soft cloth and/or filtered pressurized air Visual inspection
Automated Cleaning Methods Gross removal of soil Arrangement of devices in washer basket Washer Disinfector Cycle (i.e. Steris 444) Pre-rinse for 2 minutes - cold water Enzyme wash 2 minutes - hot water Wash 2 minutes - hot tap water (60 C set point) Rinse for 2 minutes - hot tap water (60 C set point) Dry for 15 minutes at 115 C Visual inspection of devices
Current testing format
Digital Image Illustrations
Automatic cleaning in washer disinfector:
Acceptance Criteria (Example) Bioburden >= 3 log reduction (1 log = 900,000, 2 log + 90,000, 3 log + 9,000 so 3 log reduction is 999,000 or less that 1,000 remains, prior to sterilization.) Carbohydrate Lower than the limit of quantitation (<1.1 µg/ml), less than we can detect on sample. Protein Lower than the limit of quantitation (<6.4 µg/ml) less that we can find on the sample.
Levels of Cleanliness (cont.) Disinfection manual for personnel safety in handling o Indiscriminate use of any disinfectant can have fixative properties on critical surgical instruments and may be counter to the individual disinfectants claims. Thermal Disinfection using the A0 concept in automated washers o Must have sufficient rinsing to prevent detergent build-up resulting in potential corrosive actions
Recommendations, Decisions, and Options. Use pre-cleaning and moist environments to maintain loosen soil. Use enzymes for devices that can be soaked. Use detergents with high rinsing formulas. Use detergents when cleaning non-soaked devices. Rinse thoroughly with high quality water. Reduce complex chemistries whenever possible. One product for all device is not best practice. If you use a disinfectant remember to rinse it off before further use or processing.
The Sterilization Validation Process As the process follows: o Contamination (simulated justified worst case) o Exposure to the minimum cycle time at the minimum sterilization temperature. o For most processes the overkill method is used. o this involved the exposure of the worst case contamination to half the minimum cycle time. Subsequently in a linear model this validates a two time log reduction.
Linear Log Reduction Illustrations
Biological Indicators (Many Types) Typical for hospital use. Various types for industry. These come as purchased products These come in many sizes and materials.
Biological Indicator Placement
Hard to reach Worse-Case testing.
Testing - Biological Indicator Placement Table
Set up
Functional Testing All products tested to the new product quality inspection procedure (this is the procedure for the device on the manufacturing floor for as built new). o After lifetime sterilization exposures (i.e. 500-1000 cycles) o After lifetime washing exposures (i.e. 500-1000 cycles) o After all repairs Functional tests are routinely done on the worst case know exposure cycle. For global company releases that sell in France this would be 18 minutes at 134 C or as high as 137 C depending on testing equipment.
Other issues in reprocessing Dry Time (not a part of sterility but a part of sterility maintenance these times are not an extended cycle) Immediate Use Sterilization (Flash) Plastic Weight Moisture Cleaner Residues - Rust inhibitors (rust present?), lubricants (oils?), enzymes (proteins?), concentrates (too much or too little?)
Other methods of reprocessing Ethylene Oxide (EO) Vaporized Hydrogen Peroxide processes Dry heat Use the same overkill type and half cycle approach but may vary target organism dependent on method.
Terminal Sterilization - SUD Radiation Gamma, E-beam Ethylene Oxide (EO) All products tested statistically to 1 in a million o (Label means 10-6 validated.) Tested products fully submerged in test media.
Everything in the jar - covered or contacted. Test is 14 days - visual turbidity is a positive.
Conclusion Every product or family of products has a methodology to which it is validated for cleaning and sterilization. All chemicals used for have consequences. Water is a powerful positive and negative. Instructions are getting better but slowly and maybe not easier. Communication is still the key to success. People remain the focus. Patient s first, but include users, processors, designers, and regulators.
Questions? rod.parker@stryker.com (269)-389-3219 North Break wall Lighthouse Ludington, Michigan USA (my hometown)