Our turnkey packaging services are ideal for sterile surgical and procedure kits where multiple components are packed together and lot control and traceability are of the highest importance. Our packaging processes are validated and we have a long track record of exceptional on-time delivery. We specialize in medical device contract manufacturing of both small and medium volume products.
We provide better quality medical device contract packaging services because we control the thermoforming process of the packaging trays. We pride ourselves on our unparalleled ability to work with heavy gauge and other difficult materials such as polycarbonate. Our thermoformed packaging capabilities include post-forming fabrication to manufacturing thermoformed packaging with vents, handles, locking tabs, and welded internal components. We also provide customized trays to support specialized lyophilization processes.
A Cardiovascular Device Company came to J-Pac Medical with a request to establish a contract packaging capability in the United States. The existing packaging flow had been established in Europe, as was the package design.
As part of the overall transfer, J-Pac proposed a total redesign of this existing package to reduce the overall footprint, as well as downgauge all packaging materials.
In addition to reducing the overall footprint and down-gauging packaging materials, our redesigned package also enabled a 40% increase in Eto Sterilization throughput. Freight gains were also realized.
There is a lot of excitement in the medical device packaging industry about pre-validated packaging.
Using pre-validated packaging may reduce time to market and minimize package development and validation expenses. However, international standards defining medical device validation requirements are complex, involving materials selection, design qualification, process validation, and design controls. Pre-validated packaging may not comply with all the requirements depending on the specific device involved. Nevertheless, pre-validated packaging can be a helpful strategy if adequately implemented by the device packager within the framework of these standards. This paper aims to clarify when pre-validated packaging makes sense and how its cost and lead time compare to a custom-designed package.
Packaging Standards for Terminally Sterilized Devices
Sterile packaging systems need to ensure the sterility of their contents until they are opened for use. The sterile barrier system (SBS) must also be designed to ensure aseptic presentation at the point of use. ISO 11607 (part 1 and part 2) is the global standard governing packaging for terminally sterilized medical devices. ISO 11607-1 defines requirements for SBS materials selection, and their design and testing. ISO Sterile packaging systems need to ensure the sterility of their contents from shipping through the point of use. The sterile barrier system (SBS) must allow aseptic presentation into the sterile field. ISO 11607 (part 1 and part 2) is the global standard governing packaging for terminally sterilized medical devices. Part 1 of the standard defines requirements for SBS materials selection and their design and testing. Part 2 defines manufacturing critical process validation requirements for forming, sealing, and assembly processes.
ISO 11607 provides precise terminology used for medical device and healthcare packaging.
Sterile Barrier System (SBS):The minimum package that minimizes the risk of ingress of microorganisms and allows aseptic presentation of the sterile contents at the point of use. For example, a thermoformed tray with a Tyvek lid can be an SBS. Header bags and Chevron pouches are standard sterile barrier systems.
Protective Packaging:The configuration of materials designed to prevent damage to the sterile barrier system and its contents from the time of their assembly until the point of use. These include shelf cartons and shipping boxes.
Preformed Sterile Barrier System:A sterile barrier system that is supplied partially assembled for filling and final closure or sealing. Examples of these include porous and nonporous chevron pouches, header and patch bags. These are typically purchased from packaging suppliers partially assembled and used during final packaging by making a final closure seal. A thermoformed tray also falls within this definition.
Packaging System:The combination of the sterile barrier system and protective packaging. Both work in tandem to protect the product and the sterile barrier.
How is Sterile Packaging Validated?
ISO 11607 and ISO 11135 define the requirements for validating terminally sterilized medical device packaging.
Design Qualification. Packaging materials must be selected and documented within a quality system based on the requirements of the device and sterilization method used. These include the adequacy of the microbial barrier, biocompatibility and toxicity attributes, sterilization effects, sealing effectiveness, compatibility of the device and SBS materials that contact each other, and compatibility with labeling.
Stability Tests. The sterile barrier seals must be proven to maintain sterility over time. Validation involves a post-sterilization stability study. The sealing and sterilization parameters for this test must be under worst-case conditions. The FDA allows accelerated stability testing if real-time testing occurs in parallel.
Sealing Validation. The sterile barrier system’s sealing process must be validated. This requires a critical manufacturing process validation, which includes an IQ, OQ, and PQ on the sealing equipment performed at the manufacturing location.
Transit Simulation. Transit testing must reflect how the product will be shipped
Sterilization Validation. Sterilization results in a 10-6probability of any infecting microbes surviving the sterilization process.
What is pre-validated packaging?
A pre-validated package eliminates the need for design qualification (1), stability testing (2), and sealing validation (3). It does not negate the need for transit testing because each packaged product may impact the seal differently. Likewise, sterilization validation is still required because it is unique to the product – not the package.
When is pre-validated packaging preferred?
Pre-validated sterile packaging is a novel concept that, if properly executed, can help MDM’s reduce
High probability package will change
A clinical trial is the next step
Low probability package will change
Commercial launch is the next step
What sterilization validation methods are typical?
The available sterilization validation methods are “full validation” and “single batch release.” A full validation validates the cycle parameters and the specific equipment. The single batch release verifies each lot separately. Three single batch releases performed in twelve months may equate to a full validation after a retrospective analysis.
Batch Release Sterilization
High probability package will change
Commercial launch in <16 weeks
Low probability package will change
Commercial launch >16 weeks
Time and cost savings
Typical project plan for pre-validated packaging
Pre-validated sterile packaging is a novel concept that, if properly executed, can help MDMs reduce expenses and improve time to market. However, the ISO 11607 standard (Parts 1 and 2) is complex and cites three critical components of a “validated” packaging system. (A) The design and development of the packaging system include material selection, design, and packaging qualification testing, (B) qualifying or validating or providing proof of the stability of the SBS materials and seals, and (C) sealing process validation.
The MDM’s unique devices, sterilization cycle, distribution environment, and manufacturing processes often require pre-validated packaging solutions to undergo additional qualification and validation testing to satisfy regulatory requirements. MDMs should ask specific questions to understand how pre-validated packaging meets these requirements and identify any further testing that may be required. Finally, MDMs must ensure that all validation data is maintained in their design history files, as they are ultimately responsible.
ISO 11607-1:2006/(R) 2010Packaging for terminally sterilized medical devices—Part 1: Requirements for materials, sterile barrier systems, and packaging systems and ISO 11607-1: 2006/A1: 2014Packaging for terminally sterilized medical devices – Part 1: Requirements for materials, sterile barrier systems, and packaging, Amendment 1
ISO 11607-2:2006/(R) 2010Packaging for terminally sterilized medical devices—Part 2: Validation requirements for forming, sealing and assembly processes and ISO 11607-2: 2006/A1: 2014Packaging for terminally sterilized medical devices – Part 2: Validation requirements for forming, sealing, and assembly processes, Amendment 1
ANSI/AAMI/ISO TIR16775: 2014, Technical Information Report, Packaging for terminally sterilized medical devices-Guidance on the application of ISO 11607-1 and ISO 11607-2.
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.
Get the guide
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 Cardiovascular Device Company came to J-Pac Medical with a request to establish a medical device contract packaging capability in the United States for an existing packaging flow had been established in Europe, as was the package design.
As part of the overall transfer, J-Pac proposed a package design and validation to reduce the overall footprint, as well as downgauge all packaging materials.
In addition to reducing the overall footprint and down-gauging packaging materials, our redesigned package also enabled a 40% increase in Eto Sterilization throughput. Freight gains were also realized. J-Pac also provided medical device cleanroom assembly as part of its medical device outsourcing services.