Determining a medical device’s shelf life can be one of the more challenging aspects of a new device development program.
It’s also one of the most overlooked.
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
With this resource, your new device development team can reduce the testing timeline and oversee a smoother, faster product launch.
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Validating Medical Device Assembly, Packaging, & Sterilization
According to the World Health Organization (WHO), healthcare-associated infections (HAIs) are the most frequent adverse event in the delivery of healthcare services worldwide. Ensuring the sterility of medical devices is a critical step in the overall effort to reduce the rate of infections in hospitals and other healthcare settings.
Medical device OEMs typically work with three separate entities for the back-end stages of product realization: medical device outsourcing companies, testing labs, and sterilization companies. It is common for these entities to focus on their particular expertise without helping the OEM navigate the process as a whole.
The best way to think about the market launch requirements of sterilized, single-use medical devices is to think in terms of how these requirements work together.
Package design is regulated by ISO 11607 (Part 1 and Part 2), and these standards are universally required by the FDA and the EU Medical Device Regulations. ISO 11607 is one of the most misunderstood standards in device development, requiring the execution of more than 25 specifications, protocols, and test reports.
Designing protective packaging to ensure the device can survive transportation stresses from the point of manufacture to the customer. One of the most common causes of packaging failures is not considering how products are shipped to customers. For example, palletized products from the manufacturer must be tested to ensure they can be delivered through sterilization, but further testing is required if those pallets are broken down and the product is shipped to customers through common carriers. Having a box thrown into a UPS truck is not the same as shipping a skid from the manufacturer. One of the most common mistakes we see is not considering consolidated shipping configurations that are used for sterilization. Orthopedic implants, in particular, generate significant stresses on packaging and are highly sensitive to shipping configurations.
Package prototyping is recommended to ensure the final package will meet the needs of the customer and will be manufacturable and optimized for final assembly of the device. Selecting a contract manufacturer with internal thermoforming and a broad array of packaging technologies can provide companies with a realistic sample of the final package much faster than having to coordinate multiple suppliers.
Package verification testing is a critical step and is often overlooked, which increases the chance that the package fails the final transit test. In this step, the final version of the product is packaged and undergoes preliminary package testing to ensure it has a high probability of passing the final transit testing. Some labs report up to 30% of their medical device packages fail the ASTM or ISTA transit tests. A preliminary transit test greatly reduces this risk. Typical sterile package verification tests include peel testing and bubble leak testing. These tests must be validated in advance.
A sterile presentation test must be conducted with actual end-users to ensure the medical device can be aseptically presented. Scrub nurse and doctor interaction with the package is critical. Some packages can be designed to deliver the device to the sterile field by allowing the device to gently “fall” out of the package onto a sterile table. Other devices require the product to be held over the sterile field while the scrub nurse manually removes the device from the package. Each of these scenarios impacts the design of the package regarding ease of opening and, for thermoformed trays, how the package is designed to be held with one hand while peeling the lid with the other.
OQ (Operational Qualification) of the sealing process. This involves challenging the sealing process parameters to create windows of variability that the process must maintain to provide an acceptable seal. It is imperative that products produced for subsequent sterilization and transit testing be produced at OQ-Low to simulate worst-case manufacturing conditions. This is often overlooked and can yield compromised packaging during ongoing production when sealing parameters drift to the low end of their specification. This requirement ensures that a seal made under the worst-case process variation will stay intact.
PQ (Process Qualification). This step involves producing product under realworld manufacturing conditions including multiple shifts and operators. The fastest path of validation involves using OQ-Low to validate post-sterilization transit and seal stability testing and PQ for final sterilization validation
Sterilization can put significant stresses on a package and also can impact the shelf life of the device. To reduce the risk of failure the medical device package must be exposed to worst-case sterilization prior to transit testing. “Worst-case” needs to be justified. A double (2X) sterilization is often used to simulate worst-case. A 2X sterilization cycle may occur when there is a sterilization cycle that needs to be aborted due to mechanical failure, or there is a need to re-label a previously sterilized product. Your contract manufacturer should coordinate a discussion with the sterilizer to determine the best assumptions.
Transit testing has two objectives. The first is to evaluate if the product and package interaction during shipping will compromise either the sterile barrier or the product itself. The second is to determine if sterilization will impact the sterile barrier irrespective of the product interaction.
An ISTA or ASTM transit test should be selected that best reflects the actual transportation and storage environment that the package will experience. There are a variety of possible distribution cycles for transit simulation including air and motor freight. Test conditions include atmospheric conditioning (e.g., humidity, temperature), compression, vibration, and shock. Testing for both palletized movement and individual shipper handling are crucial considerations.
ISO 11607 requires proper documentation and a rationale for the use of a particular test along with detailed conditions under which the sterile barrier must be maintained.
Always conduct seal tests with empty packages. This allows the sterilization effect on the package seal to be independently evaluated. There are many reported cases where package design has been changed unnecessarily because there was not independent testing of the seal. In essence, if the seal is not tested independently and the transit test fails, the customer will not know if the failure was caused by the seal design or the impact of the product. Costs are increased because tests must be repeated, and product is wasted. Similarly, testing full packages increases the volume of product that needs to be manufactured for the test.
Seal tests can involve several ASTM test methods with the most popular being the bubble leak test, visual seal inspection, and peel strength testing. These tests are performed after both accelerated and real-time stability testing. The FDA will accept accelerated shelf life testing as long as real-time testing is completed in parallel. The desired shelf life dramatically impacts the cost of the test due to the sample size and test time required.
Accelerated shelf life testing allows the product to be launched more quickly and can be critical to supporting clinical trials. A one-year shelf life label can be accomplished in just 46 days of accelerated aging; this is adequate for clinical testing. Two types of stability tests must occur: tests on the seal design and tests to ensure the packaged device does not negatively impact the seal. The medical device must also be tested to ensure its functionality is acceptable for each point of shelf life testing (1 yr., 2 yr., etc.).
First is validating the desired load size for ongoing production. This method requires that the planned batch size be validated as a group. For example, a four-pallet Eto chamber process can be validated with four pallets of packaged product or a smaller amount of packaged product with dunnage that simulates the density of the larger load. This can be an impractical method for new product launches because it often requires more product to be produced than needed for initial market launch.
The second popular method is “single lot release.” This is accomplished by sterilizing three separate smaller lots of product and then performing a retrospective study to create a validated sterilization process. All three lots must be processed within one year. The single-lot release is a sterilization verification method — not a validation method — because each lot is tested to verify its sterility. This is often more expensive than validating a larger load but is often the most practical approach.
Timing and costs can vary greatly depending on the medical device validation strategy deployed as well as how coordinated the individual processes are managed. Your medical device outsourcing partner should provide a detailed schedule of timing and costs for various scenarios. This timing must also be integrated into the higher-level product development plan. It is very typical for customers to be surprised by the length of this process which often delays 510(k) submissions.
These are typical lead times, but they can be significantly reduced by selecting an outsourcing partner well versed in all aspects of the process as well as having vertically integrated packaging and manufacturing processes.
A Summary of JAMA Viewpoint April 29,2020. Dpi:10.1001/jama.2020.7477. “Moving Personal Protective Equipment into the Community, Face Shields and Containment of COVID-19”
Eli N. Perencevich, MD, MS; Daniel J. Diekema, MD, MS; Michael B. Edmond, MD, MPH, MPA
The purpose of this white paper is to summarize the key points made in a JAMA published Viewpoint regarding using PPE in the general public. Please refer to the article referenced for specific information. J-Pac makes no claim about the article’s accuracy and this white paper provides an initial overview for the reader.
Transmission of SARS-CoV-2
The JAMA Viewpoint describes evidence that the virus is spread like other respiratory viruses; infected droplets emitted from the respiratory system of an infected individual penetrates the mucus membranes of the eyes, nose or mouth of a non-infected person. Smaller droplets are able to travel further than the 6 ft recommended distancing guideline.
[J-Pac Comment] Chinese supply of face masks became a major liability during the pandemic. Healthcare providers were often able to secure face masks from China. Many of these masks are sold by distributors as rebranded products with sourcing information hidden from the consumer.
To help preserve face masks for healthcare providers, the Centers for Disease Control and Prevention recommended that the general population use cloth face masks in public to control the spread of the virus. However, they have been shown to provide a low level of protection compared to N95 respirators.
The author suggests that medical face shields may provide a better option to cloth masks. Medical face shields provide a clear plastic barrier that covers the face. They appear to reduce the transmission of the influenza virus. In one study, face shields were shown reduced exposure by 96% when worn within 18 inches of a cough. When the distance was increased to 6 feet, the face shield reduced inhaled virus by 92%.
Adding medical face shields to currently advised containment strategies appear to be an improvement that should be studied further. While not perfect, even vaccines for most infectious pathogens do not require 100% efficacy and the author urges that requiring medical face shields to meet 100% efficacy is not required to drive SARS-CoV-2 to manageable levels.
Much is still being learned about the novel coronavirus (SARS-CoV-2) that causes COVID-19. Current studies confirm that the virus spreads most at close distances via respiratory droplets. On the other hand, transmission of the virus from person to person from surfaces is less clear. Current evidence indicates that the virus can stay alive on surfaces for hours to days. The CDC recommends that cleaning and disinfecting surfaces is a best practice for the prevention of COVID-19.
Cleaning vs Disinfection
What exactly do we mean by “Cleaning and Disinfecting” a J-Shield? It is helpful to think of cleaning as the removal of dirt, germs and impurities from surfaces. In general, it does not kill all the germs, but does reduce their level on the surface. Disinfecting, on the other hand, does kill germs and does so more effectively if the surface has been cleaned beforehand. Surface dirt can react with the chemicals in disinfectants, rendering them less effective. It’s highly recommended to clean before disinfecting.
What is Isopropyl Alcohol?
Isopropyl alcohol (2-propanol), also known as isopropanol or IPA, is the most common and widely used disinfectant within pharmaceutics, hospitals, cleanrooms, and electronics or medical device manufacturing. There are different solutions, purity grades and concentrations that yield different results.
The term, “70% IPA” means that the disinfectant solution has 70% Isopropyl Alcohol and 30% purified water. Likewise, “90% IPA” means the solution contains 90% Isopropyl Alcohol and 10% purified water.
IPA works by penetrating the cell walls of the organism and coagulating its proteins, after which the organism dies.
Isn’t a Higher Level of IPA Better?
Not necessarily. Higher concentrations of alcohol do not result in more desirable disinfection. Likewise, concentrations below 50% make the effectiveness of IPA dramatically less.
Water is a very important ingredient to help destroy bacteria, fungus, and viruses. It acts as a catalyst and plays a key role to denature the proteins of cell membranes, making them able to be destroyed. Once the cell wall has been penetrated by the IPA, the organism dies. Water helps this process go faster and more efficiently. One way it does this is by slowing down the evaporation of the alcohol, allowing it to stay on the surface of the J-Shield longer. A higher concentration of alcohol can actually hinder disinfection because it more quickly causes protein coagulation, which then forms a film that prevents further protein coagulation.
Non-Porous vs Porous Face Shield Materials
Because J-Shields are made from medical grade materials that are non-porous, they can be easily cleaned and disinfected as any other hard, non-porous surface such as tabletops and doorknobs. This makes J-Shield unique. Other shields may use open cell foam, elastic bands or Velcro that create a sponge-type property that complicates cleaning and disinfection. These materials absorb sweat, germs, dirt and cosmetics and cannot be quickly cleaned reliably.
How to Properly Clean and Disinfect the J-Shield
The cleaning process is simple. It consists of two steps:
Inspect the shield and discard if damage is found.
Wash all surfaces in a warm soapy water solution.
Wipe dry with a clean soft cloth or air dry. Air dry will reduce the chance of scratching the visor.
Wipe the shield from inside out using a 70% IPA solution.
Allow IPA to contact the shield materials for the recommended time specified by the IPA manufacturer. Contact time is very important and different brands claim different contact times.
70% IPA is an efficient and effective solution for cleaning hard, non-porous surfaces. The J-Shield is designed with special medical grade materials that are non-porous, preventing the sponge-like fluid absorption that inhibits cleaning. J-Shields are best cleaned by washing with soap and water, followed by disinfection with a 70% IPA 30% Purified Water solution. These disinfectant solutions are relatively cheap and easily obtainable.
About J-Pac Medical
J-Pac Medical is a manufacturing outsourcing partner to medical device OEM’s seeking a faster time-to-market and dependable long-term supply. We specialize in single-use medical devices, biomaterial implants, and lab-on-chip diagnostic consumables. J-Pac delivers a validated end-of-line solution for package design, cleanroom assembly, sterilization, and supply chain management. We are FDA registered and certified to ISO 13485:2016.