Dec 16, 2019 | MDR, Regulatory, Technical Expertise
Do you have the capabilities to conduct chemical characterization, toxicological risk assessments and biocompatibility testing in-house?
MDR requires that medical devices undergo a complete biological risk assessment to evaluate chemical, toxicological and biocompatibility conditions before they are approved for market. When developing a test plan, look for a partner that offers all three analytical tests under one roof. A lab that is skilled in all areas and uses highly sensitive analytical methods increases efficiency and helps address all biological endpoints, while minimizing room for error between tests. Working with a partner that doesn’t have all of these capabilities may leave you with no choice but to piecemeal your testing, which could risk miscommunication between parties, loss of information altogether, increased costs and longer timelines. Given the looming deadlines, there is no time to spare.
What is your track record for complete identification?
MDR will place increased emphasis on the importance of chemistry and toxicology. For this reason, working with a lab that specializes in complete chemical characterization will yield the best results. Ask how long they have been conducting extractable/leachable (E/L) studies and how sensitive their analytical methods are. It may be a red flag if their test methods can’t detect chemicals above the analytical evaluation threshold (AET). If a lab doesn’t use proper methods or equipment, they may not be able to provide the right data for a toxicologist to fully assess risks. Unidentified chemicals or incomplete risk assessments will endanger your entire submission package. You should look for a lab testing partner staffed with experts who can demonstrate a track record of regulatory success.
What is your approach to reporting unknown chemicals? How often do you report unknowns?
Complete chemical characterization requires identification of every chemical compound in your device found above the AET. While there are commercially available libraries that can help identify some chemicals present in extracts, they are not necessarily reliable in every circumstance. Reporting unidentified compounds can result in an unfavorable risk assessment, which could send you to the back of the line for another round of testing. Having to retest products increases cost and lead times. Ensure your partner has the ability to identify every compound the first time around.
Do you offer follow-up support once a submission is ready for regulatory approval?
While the testing process is of the utmost importance, seeking out a partner that also provides post-submission support ensures everything runs smoothly from start to finish. If regulators have questions or ask for additional information, your partner should be available to provide guidance. When it comes to MDR, partnerships shouldn’t end until regulators deem your submission approved and products ready for market.
How does your staff stay up-to-speed on the changing regulatory expectations?
You will want to work with a lab testing partner that is staffed with experts who sit on regulatory committees, are in-the-know with the evolving regulatory landscape and have been doing chemistry, toxicology and biocompatibility on medical devices for several years. Do your due diligence in learning about a lab or CRO’s involvement with regulatory bodies before inking any agreements, so that you can be confident in your submission package.
These questions will put you on the right path to gauge whether a potential testing partner is capable of meeting your needs. To learn more about how to get the most out of your testing services, read “How to maximize your lab partnership: Details pay dividends.”
WuXi Medical Device Testing offers testing services in St. Paul, Minn., Atlanta, Ga., and Suzhou, China.
Nov 17, 2019 | MDR, Medical Device, Regulatory
Medical device manufacturers around the world are working to ensure their package designs are in line with the recent updates to ISO 11607, Part 1 and Part 2, and the Medical Device Regulation (MDR). Britt Jones, WuXi AppTec’s manager of package testing services, answered five key questions about the ISO 11607 revisions to help explain how they will affect your products and preclinical device safety test plan under MDR.
1. What are the goals of the revisions to ISO 11607, Part 1 and Part 2?
The changes are designed to enhance patient safety and create globalized harmonization with other standards. By putting stricter packaging requirements in place, product handling by clinical professionals will be more intuitive and contamination risk will be lowered.
2. What’s the interplay between these changes and MDR?
Updates to ISO 11607 should help with MDR compliance because the goal of the revisions is to harmonize the standards with the General Safety and Performance Requirements of the MDR. From an MDR standpoint, packaging failure or the inability to demonstrate package integrity per the revised standards could have serious business implications. Noncompliance could result in a product being pulled from market, unforeseen costs associated with package redesign and/or retesting, or brand reputation damage if packaging fails and causes a patient safety issue. While the requirements align closely, testing procedures vary. Under ISO 11607, testing will be required for manufacturers to comply; but, under MDR, retesting is not necessary unless thorough justification isn’t possible with currently available data. Because many legacy products under MDR will require more evidence than what exists in company records to comply, in most cases, testing will be inevitable with both standards. Determining the required tests for validation under ISO 11607 will involve a risk analysis under ISO 16775.
3. How will new usability requirements impact package instructions and testing?
The goal of the usability requirements is to provide clinical staff with necessary instructions for use. Instructions must identify a clear location on the package to begin opening it, provide instructions on the opening technique, and describe how to present the product into the sterile field while preventing contamination and damage to the contents. Proper instructions for use are critical to infection prevention efforts and patient safety. Also, manufacturers will now be required to complete usability studies that prove the instructions are effective and intuitive.
4. In what ways have sterile barrier system requirements intensified?
Regulators now need to see that a sterile barrier system’s configuration will remain intact and prevent the possibility of microbial contamination. Packaging should guide clinicians on how to inspect package integrity before use to ensure contents are presented aseptically. And packaging should provide clear steps for safe and proper use, so that the product remains sterile from the time the barrier is broken to when it’s used.
5. How has terminology changed with the updates?
The terminology used by various regulatory bodies has been inconsistent in the past, but the changes to terminology in ISO 11607 will finally create alignment. The language also aims to harmonize definitions with ISO 11139 and establish a globalized understanding around proper packaging, labeling practices and integrity testing. It’s important to understand that device history files and regulatory submissions are not complete without package validations. Ensuring all your devices and packaging are compliant with updated standards by the May 26, 2020 MDR deadline probably seems daunting, but you don’t have to go through the process alone. For more information or to secure your spot in line with WuXi Medical Device Testing, visit https://medicaldevice.wuxiapptec.com/contact-us/. WuXi Medical Device Testing offers testing services in St. Paul, Minn., Atlanta, Ga., and Suzhou, China.
Nov 17, 2019 | MDR, Package Design, Package Testing, Regulatory
ISO 11607 and MDR—package testing and validation impacts
Medical device manufacturers around the world are working to ensure their package designs are in line with the recent updates to ISO 11607, Part 1 and Part 2, and the Medical Device Regulation (MDR). Britt Jones, WuXi AppTec’s manager of package testing services, answered five key questions about the ISO 11607 revisions to help explain how they will affect your products and preclinical device safety test plan under MDR.
1. What are the goals of the revisions to ISO 11607, Part 1 and Part 2?
The changes are designed to enhance patient safety and create globalized harmonization with other standards. By putting stricter packaging requirements in place, product handling by clinical professionals will be more intuitive and contamination risk will be lowered.
2. What’s the interplay between these changes and MDR?
Updates to ISO 11607 should help with MDR compliance because the goal of the revisions is to harmonize the standards with the General Safety and Performance Requirements of the MDR. From an MDR standpoint, packaging failure or the inability to demonstrate package integrity per the revised standards could have serious business implications. Noncompliance could result in a product being pulled from market, unforeseen costs associated with package redesign and/or retesting, or brand reputation damage if packaging fails and causes a patient safety issue. While the requirements align closely, testing procedures vary. Under ISO 11607, testing will be required for manufacturers to comply; but, under MDR, retesting is not necessary unless thorough justification isn’t possible with currently available data. Because many legacy products under MDR will require more evidence than what exists in company records to comply, in most cases, testing will be inevitable with both standards. Determining the required tests for validation under ISO 11607 will involve a risk analysis under ISO 16775.
3. How will new usability requirements impact package instructions and testing?
The goal of the usability requirements is to provide clinical staff with necessary instructions for use. Instructions must identify a clear location on the package to begin opening it, provide instructions on the opening technique, and describe how to present the product into the sterile field while preventing contamination and damage to the contents. Proper instructions for use are critical to infection prevention efforts and patient safety. Also, manufacturers will now be required to complete usability studies that prove the instructions are effective and intuitive.
4. In what ways have sterile barrier system requirements intensified?
Regulators now need to see that a sterile barrier system’s configuration will remain intact and prevent the possibility of microbial contamination. Packaging should guide clinicians on how to inspect package integrity before use to ensure contents are presented aseptically. And packaging should provide clear steps for safe and proper use, so that the product remains sterile from the time the barrier is broken to when it’s used.
5. How has terminology changed with the updates?
The terminology used by various regulatory bodies has been inconsistent in the past, but the changes to terminology in ISO 11607 will finally create alignment. The language also aims to harmonize definitions with ISO 11139 and establish a globalized understanding around proper packaging, labeling practices and integrity testing
It’s important to understand that device history files and regulatory submissions are not complete without package validations. Ensuring all your devices and packaging are compliant with updated standards by the May 26, 2020 MDR deadline probably seems daunting, but you don’t have to go through the process alone. For more information or to secure your spot in line with WuXi Medical Device Testing, visit https://medicaldevice.wuxiapptec.com/contact-us/.
WuXi Medical Device Testing offers testing services in St. Paul, Minn., Atlanta, Ga., and Suzhou, China.
Oct 8, 2019 | MDR, Medical Device Testing, Regulatory
With the MDR journey well underway, device manufacturers should have their gap analyses complete and road maps to the finish line thoroughly planned out. However, the industry is behind.
Where OEMs Are Now vs. Where They Should Be
Many manufacturers are running behind with their MDR implementation. Depending on how many products they need to test and who is carrying out testing, the process can take months or even years. Many small and mid-size companies are not ready due to limited resources, lack of regulatory knowledge, or simply not knowing where to start. Companies with a larger volume of products may be more at risk, especially if they haven’t begun prioritizing products. However, those with fewer products and less ground to make up should already be working toward MDR compliance. If they’re not, it’s time to put the pedal to the metal.
Deciding on a Path Forward
OEMs have two options to complete pre-clinical device testing. The first is to conduct their own testing using in-house facilities and personnel. Companies that do not already have facilities up and running would have a lot to accomplish before testing can even begin; at this point, building an in-house lab may not be feasible. The alternative option is to outsource testing to a specialized lab or contract research organization (CRO). There are pros and cons to each approach, and selecting the best path forward comes down to several factors unique to the device manufacturer. Following are some criteria to help determine the best path forward.
The Pros of In-House Testing
There are a few advantages to having an in-house testing facility:
- Ownership: Owning the medical device testing process grants a company control over the whole project, from technical insights and cost through timing and submission decisions, etc. Most importantly, medtech firms can re-prioritize products in real-time, if challenges arise. Due to the high demand for testing services in the face of MDR, laboratory testing facilities continue to experience capacity constraints. Handling projects internally allows organizations to avoid competing with other companies for priority or dealing with the headache of securing a spot in line.
- Direct lines of communication: Internal communications may be easier and more efficient because it eliminates outside involvement and could shorten response time.
If an organization elects to take testing in-house, it’s essential to consider the steps needed to run a viable testing facility. As long as the internal team is aware of the latest testing standards, regulatory expectations, has experience with extractables and leachables (E/L) studies, and has written risk assessments on medical device products in the past, they should be in good shape. But be aware the cost savings associated with in-house testing may be offset by the expense of building an internal facility and purchasing standard lab equipment (the latter alone could cost millions of dollars).
Pros of Outsourcing Testing
The greatest downfall of in-house testing ahead of MDR is the unforgiving timeline. In-house testing requires physical space, technology, personnel, expertise, equipment, and more to execute successfully. If a company doesn’t already have these, now may not be the time to take a DIY approach. Due to labs’ specialization, analytical methods, and regulatory knowledge, going the outsourcing route may be the better option for MDR testing. Here are a few reasons why:
- Reputation: Working with a lab may help boost submission credibility in regulators’ eyes. Regulators want to ensure companies have not introduced any biased views in technical files and chemistry reports. Involving an unbiased third party is one way to accomplish this.
- Access to insider knowledge: In-house testing facilities in their infancy won’t have access to extensive chemical databases, as these libraries are built slowly over time. CROs, on the other hand, have visibility to all types of products, regulations, new standards, and questions or requests that may come from regulatory agencies. This visibility allows experienced lab testing partners to adapt quickly and draw upon broad exposure and experiences when dealing with the unexpected. Learnings gleaned from identifications can be leveraged to inform decisions and trends. This process can be harder for in-house labs.
- Recruitment: Staffing an in-house facility with qualified experts can be a complicated, drawn-out process. It is important to hire seasoned chemistry and toxicology experts versus generalists, as experience in the field of medical device testing will make a big difference. Similar to how there are many types of doctors, there are specialized toxicologists and chemists. Some scientists may appear qualified at first glance, but may not have previous experience with E/L testing medical devices, identifying unknown chemicals, or addressing the immune response or toxicity of a specific chemical. Risk assessments require specific tools and methods, and staff must know how to use proper analytical methods. Think of it this way: It wouldn’t be wise to have a primary physician attempt open-heart surgery. Specialization in the field of medical device testing works the same way.
- Timeliness: MDR is a big task, but outsourcing some work to a qualified lab can help reduce the burden of staffing and training, allowing for more focus on other critical tasks. Further, a lab is a good option to ensure testing is done sequentially and all biological endpoints are met. Establishing strong partnerships increases efficiency and eliminates the potential for miscommunication between parties or gaps in information.
Even if outsourcing all testing isn’t the desired route, building a relationship with a lab can help in emergencies, such as equipment failing, staff turnover, or projects outside staffs’ expertise.
General Advice for MDR Planning
Aside from which approach an organization takes to testing, knowing general guidelines is helpful throughout the approval process. Carefully prioritize product lines. Focus on products that have the highest market demand and return on investment. Finally, approach partnerships with transparency—be forthcoming with details, and give lab partners visibility to forecasts, intervals, and timelines. Providing as much detail up front as possible, setting aside privacy concerns, and sharing honest feedback helps ensure long-term success.
There’s no time left to procrastinate, so companies should keep their foot on the gas and take charge of their approach to MDR.
Sep 1, 2019 | MDR, Package Testing, Regulatory, Technical Expertise
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.
Language Harmonized
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.
Usability Evaluation
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.
