Determining a medical device’s shelf life — the term or period during which it remains suitable for its intended use — can be one of the more challenging aspects of a new device development program.
It’s also one of the most overlooked.
One reason for its difficulty is that internal factors like component interactions or degradation will influence a manufacturer’s shelf life claim.
Another is that external events such as manufacturing, sterilization, shipping and storage can impact how long a manufactured device maintains its fitness for use. For a shelf life claim to hold up, developers must simulate those events.
Owing to these variables, the process for establishing medical device shelf life is quite complex and involves rigorous testing. And in our view, there’s a specific strategy for developing these tests that sets medical device manufacturers up for long-term success.
In this white paper, we’ll cover:
- How shelf life is defined and the role a risk assessment plays in establishing shelf life
- How the ISO 11607-1 and -2 standards contribute to establishing shelf life
- Suggested shelf life testing procedures and testing requirements
- Our view of the ideal shelf life testing strategy
Defining shelf life and assessing risk
The United States Pharmacopoeia (USP) defines shelf life as “the extent to which a product retains, within specified limits and throughout its period of storage and use, the same properties and characteristics that it possessed at the time of manufacture.”
In short, it’s the duration in which a product’s characteristics can be expected to remain stable.
Note how “shelf life” differs from a product’s “useful life.” The former describes a stability expectancy prior to use. The latter describes the duration of a product’s viability during the time of use or the number of uses.
Medical device manufacturers should take a risk-based approach to determining the potential impact for using a device that may no longer be fit for use as this impacts the level of analysis. Some devices will experience degradation over time and the risk of that degradation must be assessed when determining specifications and tolerances for manufacturing and components.
Considering criteria that impact shelf life
Designers must consider many criteria that will impact the shelf life of their device. These are specific to the device in question but may include:
Chemical – including degradation, interactions with packaging and manufacturing process impact.
Physical – including mechanical properties of components and the assembled device, appearance and impact of manufacturing on the device.
Microbiology – including sterilization, package integrity and microbial load.
Toxicity – does degradation cause toxicity?
Biocompatibility – does this change during storage or use?
Packaging – the selected packaging method may impact the shelf life.
Transportation – the physical and environmental impact of shipping the product from manufacturer to the customer.
Sterilization and sterilization method – these are variably effective depending on how devices and their packages are designed. Read about these dynamics in more detail in this article.
Storage conditions – including the impact of temperature, humidity, air pressure, airborne contamination, visible light and radiation.
Special components – these may have unique expiration features, such as batteries. Sterilization and sterilization method – these are variably effective depending on how devices and their packages are designed. Read about these dynamics in more detail in this article.
The ideal shelf life testing procedure
While developing the testing procedures that help manufacturers establish a device’s shelf life, it’s just as important that they are well-documented.
For one thing, the design documentation generated during testing is vital to the eventual approval for sale of a new device. For another, developers need a strong procedure for establishing a shelf life to avoid mistakes or oversights that could sink a program in later development stages.
A good procedure should include the following sections:
- A description of organizational responsibilities for the phases of shelf life testing. There must be clear accountabilities at every stage.
- A finished device sampling plan including the number of finished devices collected, frequency of sampling, sample selection criteria and lots to be sampled.
- A raw material component and medical device package design and validation plan that determines how raw materials and packaging impacts the shelf life of the device.
- A plan for the worst case sterilization exposure that precedes packaging system and stability performance tests.
- A plan for the storage of shelf life samples which includes sample storage conditions.
- Accelerated aging parameters with results supported by real-time testing.
- A plan for the simulation of stresses induced during shipment.
- Follow-up procedures that outline the steps taken as a result of the shelf life testing. For example, setting limits on the time sensitive raw materials can be stored and methods of stock rotation.
As a turnkey medical device assembly and packaging provider, J-Pac Medical has developed deep experience developing and documenting robust shelf life testing procedures. In addition, we support the infrastructure necessary to perform preliminary shelf life studies.
Often, medical device OEM’s change their shelf life labeling over time. We recommend including your shelf life testing protocol in your FDA 510(k) so that these changes may be made without resubmission. This is possible if the change does not impact product safety or effectiveness.
How ISO 11607 relates to medical device shelf life
Frustratingly, the U.S. Food and Drug Administration and other regulatory bodies do not neatly spell out how medical device manufacturers should conduct shelf life test.
They do recommend categories of factors that manufacturers should consider, with the contents of ISO 11607 being the most widely adopted.
ISO 11607-1 defines requirements for sterile barrier system (SBS) material selection as well as design and testing. ISO 11607-2 defines manufacturing packaging process validation requirements for forming, sealing and cleanroom assembly processes. Too frequently, medical device contract manufacturers do not include assembly process validation as part of the equation.
Guidance on navigating the complexities of ISO 11607 and other applicable standards and criteria is provided here.
Pulling it all together: a typical validation process
Shelf life is impacted by both internal and external influences. Internal influences include degradation of the device itself due to component or material interactions. External influences include medical device sterilization, stress due to shipping and storage conditions that impact fitness for use.
It’s important to understand that two different systems are tested in parallel to determine a product’s shelf life: the medical device itself and the sterile package that protects it.
Conduct worst case packaging and sterilization
Before conducting validation testing, the sterile package should be manufactured under worst case conditions, namely conducting the package sealing process at the low end of the process specifications (OQ minimum) and conducting worst case sterilization (extended exposure).
Packaging System Validation
#1 – Packaging performance testing (ISO 11607)
The package’s ability to protect the product and the sterile barrier is tested after simulated transportation. The simulated transportation standard is selected based on the expected shipping method (e.g. shipped by pallets or individual boxes or both) as well as environmental exposures (e.g. expected temperature and humidity exposures).
Typically the OEM conducts testing to evaluate the protection of the product and a lab evaluates if the sterile barrier has been damaged.
Seal stability testing (ISO 11607)
The stability of the sterile seal must be tested to determine the shelf-life of the seal. This may be performed with or without the product inside the package. The testing is performed under both accelerated and real-time aging. The benefit of conducting this testing without the product is that the accelerated testing conditions applicable for the seal stability evaluation may be too aggressive for the products. In this case a different accelerated test protocol can be used for the product separately.
Product stability testing
The stability of the product is determined by its fitness for use as determined by medical device manufacturer design engineers. Product testing can take many forms including material strength testing, visual inspection and functional testing. These tests should be conducted on packaged product that underwent worst-case sterilization and simulated distribution.
Accelerated testing helps manufacturers get their products to market faster, but real-time data must be furnished post-launch to confirm accelerated testing results.
Long-term benefits of a two-prong testing approach
J-Pac recommends that developers conduct device stability studies separately from SBS stability studies. We believe this for a few important reasons:
One is that most SBS stability studies are conducted on an accelerated aging basis. The temperatures that are appropriate for SBS materials may not be applicable to device materials.
For example, an adhesive-coated Tyvek lid sealed to a thermoformed PETG tray can be safely subjected to an accelerated aging temperature of 55 degrees Celsius (131 degrees Fahrenheit). But this elevated temperature could corrupt the device materials inside the package. The degradation that can occur at that temperature would jeopardize what ordinarily would be a successful SBS stability study.
The bottom line: Don’t needlessly expose device materials to testing conditions that won’t occur during ordinary shipment, storage or use.
Another argument in favor of separating device and SBS stability tests is that when devices are included with the SBS, they often interfere with many of the tests that are conducted on the system at each aging interval.
For example, the aging intervals in SBS stability studies often go out to five years or more. This norm anticipates that a variety of devices may be packaged using a common SBS.
But devices themselves often have a functional shelf life that’s much shorter than five years. Combined testing forces a lowest common denominator, unnecessarily weakening the shelf life claims you could make for a SBS.
What’s more, manufacturers who include devices in their SBS stability studies tend to tie that particular device to that specific SBS. As a result, they often feel it is necessary to repeat the stability study on the same SBS if a different device is packaged in it.
This is not necessary.
It is much better to keep SBS stability studies independent of device stability studies. You can see the flexibility this strategy provides to manufacturers. In such a case, medical device manufacturers could:
- Build the device samples for aging tests
- Place the samples in an established SBS
- Sterilize the samples to the maximum exposure
- Evaluate only the devices for their aging stability
An immediate benefit of adopting this strategy is the potential for reducing the testing timeline and associated effort, contributing to a smoother, faster product launch.
A longer-term benefit emerges when manufacturers engage with assembly and packaging partners early in program development. Partners with design-assist capabilities can help your engineers design packages and then develop and conduct tests on SBS materials that work for a wider range of device types.
Program development guidance from J-Pac Medical
It’s a good thing that the stability testing required to establish medical device shelf life is so rigorous. Patients’ continued confidence in life-saving or life-sustaining products depends on it.
Engineering experts at J-Pac Medical help medical device manufacturers balance their obligation to patient safety with the need to meet program development timelines and commercialize their products faster.
If you’ve struggled with the testing required to establish shelf life in the past, or you lead a new company and have never done this before, consider talking with a J-Pac engineer today.