Updates to ISO 11607, Parts 1 and 2, have left many medical device manufacturers wondering about the future of their packaging designs. These changes come at a stressful time for OEMs, as Europe is also in the process of replacing the current Medical Device Directive (MDD) with the Medical Device Regulation (MDR) in 2020. The interplay between ISO 11607 and MDR is complex, and it’s difficult to predict regulators’ plans for enforcement.
ISO 11607 Parts 1 and 2 will have regulators looking to see that device packaging complies with integrity, usability, and sterile barrier requirements and that any potential risks have been mitigated. One misstep could mean cost overruns, retesting, market delays or not making it to market at all. It may seem like a regulatory and business burden now, but in the end, these updates will align with the General Safety and Performance Requirements (GSPR) and MDR.
Regulators in Europe and the United States are working to establish a baseline for preclinical device safety testing that will provide clarification of expectations across the board. Here’s how new definitions, usability evaluations, and sterile barrier requirements may impact planning and testing processes.
The first objective of the ISO 11607 updates is to harmonize terminology used throughout international standards documents and across markets. Previously, there was a lack of uniformity between global standards and regulatory bodies, making it difficult to define and link terminology across borders. ISO 11607 Parts 1 and 2 will bring consistency to the forefront. The goal is that expectations set in the United States, Europe, and around the world clearly outline requirements for packaging, labeling, and integrity standards uniformly. The updates will also harmonize terms as defined in ISO 11139.
The second change to ISO 11607 introduces a package usability requirement. This addition aims to reduce infection risks associated with how clinical staff handles devices and packaging in the sterile field. The usability requirement relates directly to impending MDR requirements.
Packaging will be required to clearly specify where to begin opening the sterile barrier system so that the contents inside aren’t contaminated or damaged. Then, it must give clear instructions on the proper opening and presentation techniques to further ensure safety. Usability studies help show regulators that instructions are intuitive and that packaging design will ensure proper use among clinical staff.
Sterile Barrier System
The third update details how the sterile barrier system should be inspected prior to use. Under the new regulation, it is critical that the product contained in the package remain sterile and allow for aseptic presentation. In order to ensure this, packaging and the sterile barrier must be strong enough to stay intact and free of breakage or microbial contamination.
Package Testing and Validation 101
The remaining variance between regulatory bodies and standards pertains to testing. With ISO 11607 Parts 1 and 2, testing to the latest standard will be a strict requirement under MDR. Determining which tests to complete may require referencing other standards, such as ISO 16775 for guidance on using ISO 11607 Parts 1 and 2 and performing a risk analysis.
For MDR, retesting is not necessarily required as long as there is sufficient justification of safety and compliance. Although MDR may seem more lenient here, the fact is that many legacy devices will still lack sufficient evidence, or a vendor or material change to the package occurred since testing was performed previously. In these instances, package integrity testing will be a safe bet.
While testing will vary by device, the following are three common aspects of package testing:
Accelerated aging and shelf life stability: The waiting period for real-time aging data can delay getting a product to market. In the meantime, accelerated aging studies can be used to establish a shelf-life limitation and create an expiration until real-time aging data is available. Aging is a multi-step process and to avoid unforeseen challenges, completing integrity testing along the way is critical. To mitigate these challenges, it may be helpful to age many samples and evaluate at various time points. Should a field issue arise, the manufacturer can refer back to the aging studies, pull real-time retains, a sample of the commercial lot, and use them to investigate real-time data.
Simulated distribution: Unexpected issues may arise, most commonly during handling, shipping, and other processes used in distribution. In order to show that the package can withstand these transitions and that process failures have been considered, the product needs to undergo simulations. These simulations include temperature manipulations and exposure times.
Package integrity and seal strength: Package integrity and seal strength limitations must be evaluated before packaging is ready for initial validation. OEMs can test the physical properties of their packaging using methods such as bubble emission, dye penetration, and seal strength. These methods achieve greater sensitivity than many microbial challenge tests.
Once necessary testing is complete, package validation should be conducted to measure the integrity of the sterile barrier system around the sterilized product after it’s been challenged. The process involves an evaluation of package stability and performance. The methods described above may be used, and the validation could also include altering the packaging configuration to test the system in a worst-case scenario.
How to Vet a Testing Partner
While new packaging standards will mean attention to detail, knowledge of the regulatory requirements, and testing, they do not mean that OEMs are on their own. It is important to partner with a highly skilled contract research organization (CRO) to ensure that testing is performed to necessary lengths and will meet all ISO and MDR requirements. That being said, not all CROs are created equally. Choose your partner based on merit and demonstrated expertise. Here are some questions that will help in the vetting process.
What are your accelerated aging capabilities? Regulators want to see that you have reliable aging results. Your CRO should perform accelerated aging tests in a variety of settings to ensure all package types and materials are compatible with the temperature being used.
Do you perform distribution/transportation testing in-house? In-house testing is preferred to mitigate additional handling and hazards associated with the distribution environment. If a CRO outsources this step, it leaves room for error.
Does your organization do environmental conditioning? Environmental conditioning testing exposes packages to freezing temperatures, tropical wet climates, and tropical dry climates for impact assessment. This data helps support a package system’s ability to withstand various worst-case scenarios. Not all CROs have this capability, but if they do, it may speak to the expertise of their staff and analytical methods.
Approach a CRO with as much information as possible so that they can provide optimal guidance. Come with details on materials, dimensions, package types, etc. It is also important to let them know what is housed inside of the sterile barrier system. If a product is fragile, testing will need to take that into account. Access to preexisting data that supports the safety of the device may be useful in preparing the shelf-life and aging studies. Also, think about distribution — are you looking for a full package or partial validation? If you’re unsure, ask your CRO what they recommend given your product and testing needs.
As is the case with all regulatory challenges, success will be difficult to achieve if you cut corners. Integrity testing and package validations are critical to ensure your design history files and regulatory submissions are in compliance with the latest standards. The only way to avoid cost overruns, wasted resources, and retesting is to start now. Prioritize selecting a trustworthy partner and providing them with all of the information they need. There is no “easy” button when it comes to achieving regulatory approval, but these recommendations will get you started down the right path.