When it comes to reusable devices, one of the many requirements in medical device development is providing detailed directions of the cleaning methods defined in the Instructions for Use (IFU). Validating those cleaning methods may seem to be a box to check before finalizing the technical files, but it carries more weight with regulators than may realize. By developing and writing the cleaning instructions within the IFU with the intent of passing the worst-case scenario in validation testing, you can help ensure that the process is robust and the documentation is on track for an efficient regulatory review.
Device complexity’s impact to testing design
When developing the cleaning instructions, consider the challenges presented to the cleaning process from the device’s geometry, the materials present, the different types of clinical contaminants and other potentially infectious materials (OPIM). Devices with complex designs – such as unique surfaces, absorptive/porous materials, or multiple lumens and small channels – may warrant a more comprehensive set of instructions for cleaning and, in turn, a more complicated construct to validation testing.
During validation testing, your partnering CRO will expose the device to a worst-case reprocessing scenario. This process includes subjecting the device to artificial soils, simulated use, reduced cleaning parameters and other challenging situations that reflect a worst-case clinical use. Lab specialists are looking for any gaps in the cleaning instructions that could arise during end-use.
A common pitfall with these instructions is a lack of robustness and clarity. For example, if a device’s cleaning instructions require the use of a brush, the user may be left wondering what the appropriate brush shape, size or material is to complete the job effectively. Providing crystal clear instructions – and even going further than you may see necessary – can minimize any guess-work and room for error.
If your device design becomes increasingly intricate, make sure your team reflects this evolution when writing the IFU cleaning instructions and planning adequate lead time to evaluate it.
“Clean” & the clinical setting
Before testing begins, determine the definition of “cleanliness” in relation to your device by deciding the testing analyte(s) that is the most clinically relevant to your specific product. Possible relevant analytes include protein, hemoglobin, and Total Organic Carbon (TOC), among others. The U.S. FDA requires that you test for at least two.[i]
In past years, the U.S. FDA accepted testing for log reductions in bacteria to demonstrate overall device cleanliness. More recently, the consensus shifted to standardize using more organically relevant analytes to assess the efficacy of the cleaning process. When remediating a device, consider testing specific analytes primarily and bacteria secondarily, as the combination is generally a more comprehensive representation of the bioburden your device will face. Make sure your testing partner is using the proper analytes to replicate your device’s clinical setting.
Fail-safes for successful testing
When completing validation testing, you shouldn’t be crossing your fingers and hoping your device passes. Enter the validation phase with confidence in your cleaning instructions by working closely with a testing partner during the development phase and using feasibility testing throughout this partnership to stay ahead of risks. Feasibility testing doesn’t have to be a critical path in device development. It can run on a parallel path without affecting the overall timeline.
These steps allow you to enhance and modify the cleaning procedure, so there are no surprises when your device reaches the validation stage. Your validation will look clean and comprehensive. In the long run, it may save you from extending timelines due to a failed validation.
IFU development is a tricky process, and it can be tempting to take shortcuts. Instead, work with a testing partner who knows the ins and outs of cleaning methods, worst-case scenarios and validation testing to make the process as smooth and seamless as possible. Don’t pull a partner in at the end just for validation – utilize their expertise throughout the IFU drafting process.
To learn more about how WuXi AppTec can help you with IFU development and validation testing, contact a representative here.
Established in December 2000, WuXi AppTec provides a broad portfolio of R&D and manufacturing services that enable companies in the pharmaceutical, biotech and medical device industries worldwide to advance discoveries and deliver groundbreaking treatments to patients. As an innovation-driven and customer-focused company, WuXi AppTec helps our partners improve the productivity of advancing healthcare products through cost-effective and efficient solutions. With industry-leading capabilities such as R&D and manufacturing for small molecule drugs, cell and gene therapies, and testing for medical devices, WuXi AppTec’s open-access platform is enabling more than 4,000 collaborators from over 30 countries to improve the health of those in need – and to realize our vision that “every drug can be made and every disease can be treated”.
For more information, please visit: http://medicaldevice.wuxiapptec.com/
[i] Guidance for Industry and Food and Drug Administration Staff, Reprocessing Medical Devices in Health Care Settings: Validation Methods and Labeling (2017)
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.