Sterile Barrier Systems (SBS), commonly referred to as “packaging”, is the system intended to contain a sterile medical device. It needs to ensure that the sterile barrier remains intact for a defined period of time (shelf-life). This is an integral component of the medical device development process as the device design and sterilization method are key inputs to choosing the package type and materials of construction for the package design. Components of a Successful Packaging Shelf-Life Study are:
- Medical device packaging testing outcomes
- Determine medical device packaging validation inputs
- Validation study design
Determine Packaging Validation Inputs – Package Designed for Sterilization
Initial inputs related to the packaging design and packaging materials are key to a successful product development cycle. Medical device packaging shelf-life validation is a lengthy study that would have to be re-started from baseline if a thorough package design is not addressed up front. As the adage says “Time is money”! Here are key device design inputs to consider:
- Determine what method of sterilization is intended to be chosen for the device as this will affect the proposed package component materials and configuration of the shipping box’s overall density
- The gaseous sterilization modalities (e.g. ethylene oxide, steam, vaporized hydrogen peroxide, etc) require packaging materials to have a breathable component within the medical device packaging to allow the passage of the gaseous sterilant into and out of the package
- Non-gaseous sterilization modalities such as gamma, electron beam and x-ray irradiation do not require there to be a breathable component, as the radiation source is able to penetrate through the sealed layers of the medical device packaging to accomplish the sterilization of the device contained with the package
- Single barrier versus double barrier package design
- Input from key opinion leaders of the device, including end users such as nurses and doctors, is essential in determining how the package would be handled and opened in the surgical suite. Gathering Voice Of the Customer (VOC) feedback helps to provide a reliable and practical package experience. Involving marketing partners early on can also be beneficial.
Medical Device Packaging Testing Outcomes – Whole Package Integrity and Seal Strength Testing Options
Determining the types of physical testing necessary to qualify the medical device packaging is dependent on both the packaging materials and the device contained within the package.
The physical tests to evaluate the packages are categorized into two (2) categories: seal strength and whole package integrity.
Seal Strength Tests
- Burst testing – ASTM F1140 involves internally pressurizing a package and determining the impact of that pressure on the package seals up to a point of rupturing
- Seal Peel Tensile (Instron) ASTM F88 evaluates the force required to separate the specific seals of the SBS
Whole Package Integrity
- Visual Inspection – ASTM F1886
- Bubble Testing: Both ASTM D3078 and ASTM F2096 involve submersion of a package (SBS) in a fluid and the application of a pressure differential to evaluate the emanation of gas bubbles which indicate a leak
- Dye Penetration – ASTM F1929 involves the wicking of a dye solution through a seal channel defect with porous materials and ASTM F3039 involves the wicking of a dye solution through a material defect or a seal channel defect on nonporous materials
Validation Study Design – Medical Device Packaging Shelf-Life Validation
Following test method assessments, protocol development will be conducted to detail the following key elements:
- Sample Preparation – There are important considerations to be taken on preparing the medical devices prior to the initiation of the shelf-life validation study.
- Seal the packaged devices within the validated parameters
- Sterilize at maximum exposure conditions
- Irradiation (gamma/ebeam/x-ray) = upper limit of the expected dose range or greater
- Ethylene Oxide = Consider double full cycle exposure, if that is a potential option for the devices
- Other gaseous sterilization processes can use the same logic
- Sample Size – This area is always a question as samples cost money and testing costs are also higher with more samples being tested. The standards specify that the sample size must be large enough to provide for statistically significant analysis with a high degree of reliability and will be dependent on corporate risk, economics, and regulatory requirements.
- Utilize in-house quality experts for determinations to satisfy your company’s requirements
- Use design Failure Mode and Effects Analysis (FMEA) to analyze the risk and criticality to determine appropriate sampling sizes
- The FDA wants 95% confidence/95% reliability = 60 samples per test
- Most companies choose 95% confidence/90% reliability = 30 samples per test
- Accelerated Aging Conditions – It is best to select the warmest available aging chamber temperature that will not degrade or damage package or device.
- ASTM F1980 is the defining standard that outlines the methods of accelerated aging
- Note: Accelerated aging is required to be conducted alongside real time aging and is not to be used as the sole determinant of package integrity studies
- Accelerated aging is based on the thermodynamic dependence on reaction rates which involves the Arrhenius reaction rate function. This is characterized as: for many common chemical reactions at room temperature, the reaction rate doubles for every 10 degree Celsius increase in temperature (Q10).
- ASTM F1980 is the defining standard that outlines the methods of accelerated aging
- Shipping and Transportation Simulation – This challenges the shipping/packaging system for the device to experience the physical forces that will be applied in real-life as part of a simulated transportation cycle.
- A determination of when this phase of the study should be conducted is based on the distribution model that the device packaging may be exposed to, or it can be conducted as a stand-alone study.
- Typically for medical devices, ASTM D4169 is utilized as it is an FDA recognized standard (recognition #14-300).
- Acceptance Criteria
- Each of the accelerated and real time aging testing results will be compared to the baseline data
- Each test conducted at a specified time point in the study can be evaluated to this baseline
- There are pass/fail criteria for the qualitative tests as well as statistical evaluation of the quantitative test data (seal peel and burst)
- Determination of significance of the acceptance criteria should be established and included in the study protocol
Medical Device Packaging Validation Process
Validating the packaging of medical devices is a critical step to ensure product sterility, integrity, and compliance with regulatory standards. The process typically follows a structured flow, as outlined below:
1. Baseline Testing
The validation journey begins with baseline testing of the sterilized packages to establish initial performance benchmarks. This includes:
- Visual and Seal Strength Testing: Evaluates the appearance and mechanical strength of the package seals.
- Visual and Whole Package Integrity Testing: Assesses the overall integrity of the packaging, ensuring there are no defects or breaches.
2. Transportation Simulation
Sterilized packages are subjected to simulated transportation conditions to mimic real-world handling and shipping environments. This step ensures that the sterile barrier system can withstand physical stress during distribution.
3. Aging Studies
To evaluate the long-term performance of the packaging system, three types of aging studies are conducted:
- 1-Year Accelerated Aging: Simulates one year of aging in a shorter time using elevated temperatures.
- 2-Year Accelerated Aging: Simulates two years of aging under accelerated conditions.
- 2-Year Real-Time Aging: Observes the packaging over a full two-year period under normal storage conditions.
4. Integrity Testing
After each aging sequence, the packages undergo final integrity tests to confirm they still meet quality standards:
- Visual and Seal Strength Testing
- Visual and Whole Package Integrity Testing
These final assessments ensure that medical device packaging maintains its sterile barrier function throughout its intended shelf life.
Conclusion
The determination of the intended shelf life for medical device packaging is a required element of the regulatory filing. This type of long-term study requires a well thought out approach from the start of the project to ensure that a costly re-start of the aging process is not needed.
Frequently Asked Questions (FAQ)
Why is transportation simulation testing important?
Transportation simulation testing is a series of controlled physical tests (some call it the Shake-Rattle-and Roll tests) to evaluate the outer shipping box’s durability to protect and maintain the integrity of the sterilized, packaged medical devices during shipment/ transport. This testing phase can be done either independently or incorporated as part of the packaging shelf-life study.
How many years should a shelf-life study go out to?
That is a company’s decision based on factors including both functionality and commercial needs. The device’s expiration date on the device label needs to be the date where all quality metrics of the device are still able to be met following all the device performance evaluations (materials and functionality over time), packaging and sterilization validation studies. If the tested time is too short then there are too many devices that will expire on the shelf and if the time is too long then there is a potential of device obsolescence while still in circulation.
Can device functionality over time be incorporated into a packaging shelf-life study?
Yes! The accelerated aging for the package integrity can definitely contain the actual device and they can be returned to the manufacturer after the package integrity testing is complete. The package integrity testing does not damage the device; therefore this can serve a dual purpose for material/device aging and package shelf-life evaluations.
