Sean Fenske, Editor-in-Chief09.06.23
The pathway for aligning medical devices to the EU’s new Medical Device Regulation (MDR) has been a bumpy one, to put it mildly. In fact, the transition from the Medical Devices Directive (MDD) has caused some to speculate the nations under the regulatory guidance could experience shortages, limited product options (as some firms plan to withdraw devices from the market), and other challenges.
That said, one of the concerns regarding the MDR—specifically, the fact that all devices must be recertified through a Notified Body to the new standard—could present an opportunity for some companies.
Since the product needs to be recertified anyway, does this open a window to making a design change? This question, along with several follow-ups, was posed to a number of industry representatives, many of whom are regulatory professionals aiding companies in their transition plans. Their feedback is shared in the following Q&A presentation.
(Author note: These questions were originally posed prior to the announcement of the deadline extension and participants were given an opportunity to update their responses following approval of the new MDR transition timeline. Some revised their comments, while others expanded on their response with a “deadline extension note,” as indicated in their response.)
Participants include:
Dr. Peter Bowness: No. MDCG 2021-25 defines legacy devices as those devices, which, in accordance with Article 120(3) of the MDR, are placed on the market after the MDR’s date of application (DoA) until the end of the transition period if certain conditions are fulfilled. Those devices can be:
As such, for legacy devices and, in particular, if the device is subject to Article 54, it’s recommended not to make design or manufacturing changes prior to MDR certification; any changes could be made in the post-certification phase.
Deadline extension note: The recent MDR extension reinforces the transition provisions concerning changes under Article 120 but raises the prospect of legacy devices being stuck in their current configuration. As the medical device market consolidates under MDR, many components or devices are being removed or not transitioned to MDR, forcing other manufacturers to make fundamental changes to their devices. The extension, therefore, may not be useful for many manufacturers, so it remains recommended to complete the transition to MDR as quickly as possible.
Dr. Linda Braddon: In Secure BioMed Evaluations’ experience, any change not supported by an identical feature of a similar device in the EU market, clinical data may be needed for the change. This could be a great opportunity to incorporate changes but I would also recommend making the changed device a line extension to the original device in case there is an issue with the changes.
Bryan Brosseau: First, I will say the EU MDR has a lot of vague content and little clarifying guidance. Therefore, interpretation of EU MDR currently varies wildly between Notified Bodies. As such, I don't think one answer is suitable for all medical device manufacturers in the current climate. The requirements for technical documentation review has been raised significantly under EU MDR. By making a change at this time, previous data supporting the safety and performance of your device may be questioned if such a change is made. However, if the right supporting data and planning is in place, it might make sense to implement the change rather than wait a significant period of time for the Notified Body to schedule and then conduct the review of the change notification at a later date. The supporting data and planning might include the results of V&V (validation & verification) testing, technical justification for the applicability of previous data to the modified device, clinical evaluation, and PMCF (post-market clinical follow-up), and/or PMS plans, which monitor any impact in the real world on safety or performance from the change.
Dr. Janelle Lauer: In some cases, they may be forced to make a change (e.g., to remove a PVC containing DEHP) based on complying with updated CMR requirements. However, I doubt they would choose to make a change based solely on the recertification process (partly because of the FDA considerations referenced in my response to that question). In my experience, the supply chain remains the primary factor driving device changes, with design changes to improve functionality coming in second.
Alpa N. Patel: Yes. For reusable medical devices, it would be a good idea to add unique device identification (UDI) to the device as this is one of the required changes for reusable medical devices. Per MDR, “Devices that are reusable shall bear a UDI carrier on the device itself. The UDI carrier for reusable devices that require cleaning, disinfection, sterilization, or refurbishing between patient uses shall be permanent and readable after each process performed to make the device ready for the subsequent use throughout the intended lifetime of the device.” The reason for the UDI system is it allows for traceability of the devices in terms of use and reprocessing cycles, and can also help with the effectiveness of post-market surveillance.
William Pratt: Generally, I’d say if it’s a change you’ll do in the near term anyway, you might consider it. Otherwise, you’ll pay twice for the product review. The process still has to conform to the new standard, and that can be time and resource consuming depending on the type of change. Any change requiring testing and/or validation can have timeline implications that might be unacceptable if the focus is on staying in the market. The regulatory authorities are overwhelmed with this conversion, so keeping things straightforward is probably a good instinct to follow.
Dr. Helin Räägel: Since the MDR recertification would require the Notified Body to review all available data on the device, adding a change would just expand the biocompatibility assessment. Companies should form a good communication channel with their Notified Body to get them involved in the assessment. This has been a good strategy to promote a two-way conversation between the company and the Notified Body, allowing the evaluation process to be more effective and smoother.
Thor Rollins: It’s not only a great time to make changes but it’s a perfect time to examine the changes that have retroactively happened over the history of the product. Many times, small changes happen with a not-to-file justification on accepting the change. When a device has a long history of use, these small changes might build on each other to equal a dramatic change that should be considered for MDR.
Christine Scifert: It is difficult to change anything right now. The DOCs are currently locked for product under MDD requirements. There is a flowchart to determine if a significant change is being made, but you also need to discuss with your scheme manager/company representative from the Notified Body. There is some variability in responses at times.
Deadline extension note: This hasn’t changed, but now this time period is extended longer so changes to existing products and new products will be difficult to do until a company has approvals under EU MDR.
Amie Smirthwaite: The opportunity is fairly limited. Article 120(3) of the MDR says devices with a valid MDD or AIMDD certificate may continue to be placed on the market until the end of the transition period, providing there have been no significant changes to the design or intended purpose. MDCG 2020-3 has several flowcharts to enable a manufacturer to decide what is or isn’t significant. It would take a lot of text to talk through all the different scenarios, but essentially (with one exception that I can think of) if something would trigger an MDR review, it would not be allowable under an MDD certificate. The exception is design changes associated with corrective actions that have been assessed and accepted by the relevant Competent Authority. So, if you think a change to a device would be more difficult to get through MDR, it probably can’t be made on the MDD or AIMDD certificate. Any change to materials, coatings, or components for Class III devices would be considered significant. Reference to materials and coatings suggests we are talking about invasive devices, and any material change to an invasive device (even in Class IIa or IIb) is normally considered significant.
Audrey Turley: Yes, I would say this is a good time to incorporate a change. During MDR recertification, a full evaluation of the device must occur anyway so it is a good time to include any changes. Especially if additional testing is already on the table for the recertification.
Meredith Price Vanderbilt: For many changes, it is unlikely there is time to get a design change completed and validated, especially with the clinical review requirements. Additionally, if your design was already reviewed under MDD, adding changes might lengthen your MDR review time if you have the same reviewing agency as you did for MDD.
Fenske: If a client approached you with this question about one of their products, how would you advise them?
Dr. Bowness: I would recommend an MDR application based on changes that are limited only to those required to demonstrate conformity to the MDR (for example SSCP, implant cards, UDI, EUDAMED, etc.) and make any design changes post-certification to the MDR.
Dr. Braddon: Get recertification on the original device and either add modifications as a line extension or go back in after recertification. New features can create new questions that could slow the process.
Brosseau: Given the high degree of inconsistency between Notified Bodies and uncertainty with respect to review timelines and EU MDR interpretation, I would advise a risk/benefit evaluation to determine the timing for such a change notification. If the change isn't required urgently due to something like supply chain shortages or if the change doesn't promise a significant improvement in safety or performance, I would advise waiting until after all EU MDR transition elements are completed. And, if the addition of a change to the review might delay EU MDR certification and, therefore, prevent access to the EU market altogether for the product, I would refrain from including the change.
Patel: I would strongly advise them to implement a UDI system for their device that is directly placed on the device and not the packaging. In addition, I would recommend they perform validation studies to ensure the UDI will remain active and legible through the use life of the device, which is a requirement of the MDR.
Pratt: The client is responsible for their own cost/benefit analysis, and the cost risks could be significant, including loss of access to the market for a longer than expected time period. Supply chain risk has been substantial in recent years, and that might actually be a driving factor in considering a change—pro and con—but the regulatory risk is similarly substantial at this time.
Dr. Räägel: We would definitely recommend writing up a document that looks at all the available information and then defines whether additional risks exist that should be followed up with additional testing. As specified in ISO 10993-1, the recertification does not necessarily mean testing needs to be re-done; the purpose of this is to verify risks have been looked at and appropriate data exists to cover those risks. If a change is occurring, this would also be addressed using this risk-based approach; identifying what has changed and what the impact is to the final finished device.
Scifert: I would ask for details on what is changing and walk through the flowchart with them to provide some initial feedback. To me, the key is making sure you’re staying aligned with your scheme manager/company representative from the Notified Body.
Smirthwaite: It would depend on the device and why they wanted to make the change, but in most instances it probably wouldn’t be allowable; if it were allowable, it probably wouldn’t be that much of a challenge under MDR either.
Turley: For device changes during an MDR recertification, it is important to understand previously gathered data that will be used to support the recertification. Then the change should be assessed to further understand any potential risk to the patient posed by the change. These two parts should then be combined to understand what testing/risk assessment is needed.
Fenske: What factors would that client need to consider before making the decision to proceed?
Dr. Bowness: The extension to the transition timelines to 2027/2028 for MDD certified devices make this an ever more likely scenario for manufacturers. There are many factors that drive this decision. Even if equivalence is taken as the conformity pathway, there still must be sufficient clinical evidence on the device. The level of clinical evidence required by MDR is greater than under MDD and is subject to higher levels of scrutiny by the Notified Bodies and MDCG. Therefore, additional data generation may still be required, in which case, it may be the manufacturer needs to run a clinical investigation anyway, negating the need for equivalence, and can thus make changes prior to the investigation. Timing is also a consideration, as the new materials would require testing. If an investigation is ongoing, there may well be time to retest the materials and bring the technical documentation in line with the changes. If the manufacturer plans to make the changes post-MDR certification, a change review will be required; the change review itself would then add to the overall timeline of marketing the new device variant. Further, if the change is driven by a noted safety concern, non-conformity, unacceptable risk, changes in state-of-the-art, or unavailability of the original materials, the manufacturer may have no option but to implement the change as soon as possible. And of course, all of these activities are not cheap.
Dr. Braddon: An evaluation of the desired modifications should be critically approached. How will the modifications be supported in the Clinical Evaluation Report?
Brosseau: The necessary supporting data for the change (V&V testing, technical justification for the applicability of previous data to the modified device, clinical evaluation, etc.), the necessary activities in the post-market phase for the change (PMCF and/or PMS activities related to the change), and the potential impact on delay in certification.
Dr. Lauer: These considerations depend on the context of the device and situation, so it is difficult to make a meaningful comment without specific details. These discussions play out like a Choose-Your-Own-Adventure story—no two discussions follow the same path.
Patel: Unfortunately, the client does not have a choice as this is a required piece for all Class 1r (reusable) medical devices. This is a new classification MDR brought on for reusable medical devices.
Pratt: Any factor that goes into the product needs to be considered from a “what can go wrong” perspective. The status quo has risks in this regard, but the change process can have unforeseen issues, unless you (at least) trial run the scenario. Einstein was big on “mind experiments,” which would be called simulations in today’s parlance. We’re going to develop more skill in systems analysis in ways we haven’t had to in the past, with a focus on the human systems involved. The more international your market is, the more varied your considerations are going to be; every national regulatory agency is awakened to the possibilities of revenue generation, so the hoops to be jumped through are multiplying.
Rollins: What is the percentage of patient contacting surface area that has been impacted by the change? The more surface area, the larger the potential risk to the patient.
Scifert: Can the change be considered not significant and does it impact your critical suppliers? You cannot add part numbers at this time to products currently under MDD.
Smirthwaite: Whether or not the change could be made on an MDD or AIMDD certificate, based on the criteria in MDCG 2020-3.
Turley: There are several considerations. What is the reason for the change? Does it occur on a patient contacting component? Will the change require extensive testing to assess risk to the patient? Can previous data be used to support the change?
Vanderbilt: I would ask if (1) they really need the European market right now, and (2) are those changes critical to further distribution. The cost of CE marking and of design changes for a CE-marked device are high, and the timelines are painfully long.
Fenske: If a company did move forward with this strategy, would it be important for them to resubmit the product to the FDA so the same device (same BOM) is being sold within each market or is it ok to have different products within different markets/regions?
Dr. Bowness: This depends on the manufacturer’s production and supply processes and the factors mentioned previously. Dual manufacturing may not be an issue, especially if the new materials are more expensive.
Dr. Braddon: Any modification for FDA would need to go through the evaluation as to whether the change could be documented or would need a new 510(k). The question as to whether it is more efficient to have one SKU or multiple SKUs for different regions is a business decision on how to manage labeling during manufacturing. Sometimes, it is easier to have separate part numbers for different regions. Other times, it is easier to have a single part number that has a universal labeling approach. This is really a case-by-case decision.
Brosseau: I would advise the company consider this as part of their assessment to proceed with the change. Specifically, they should use FDA Guidance documents "Deciding When to Submit a 510(k) for a Change to an Existing Device" or "Modifications to Devices Subject to Premarket Approval (PMA) - The PMA Supplement Decision-Making Process" to assist in determining if change notification to the FDA is even required. If a change notification to FDA is required, determining if multiple SKUs is acceptable to the company from an operations perspective would be the next decision. I think we are generally headed toward splitting product codes for situations such as this, especially with the increased EU MDR requirements around information provided with devices.
Dr. Lauer: I doubt the companies want to have different devices in different markets and I know of no specific examples of this choice being made. Some minor changes will not trigger a full suite of tests in most markets, but a biological risk analysis would be needed to review the details of the device and proposed change(s) to determine which tests may be necessary.
Patel: Although the UDI is not a requirement for FDA, I can foresee this as a criteria FDA might look into in the future.
Pratt: Depending on the change, FDA might not require it. We already contend with localization for labelling, but a different product line in a material sense is a different product line; it’s an additional burden to maintain and it eats into the economies of scale. Again, cost/benefit has to be considered. Obviously staying in a market or not is the first big decision. Europe is getting cut out of many company’s plans; it’s not worth the expense or drain on resources. I wouldn’t be surprised if European companies drop some product lines out of their own market. It’s all about triage at this point.
Dr. Räägel: From a biocompatibility perspective, if a change is minimal and doesn’t affect the function or overall biocompatibility assessment, then for the FDA, a letter to file may be sufficient (without a new submission) if a device is already cleared for the U.S. market. Regardless, it is very important to keep good documentation on the assessments to ensure it is clear what has been changed and why it does not impact the final finished device. It should, however, be recognized that it’s ok to have different products marketed in different regions.
Rollins: The FDA does provide guidance on when to submit a new 510(k). If the change is minimal, you can follow that guidance and not resubmit. If not, a new 510(k) is needed.
Scifert: It is acceptable to have different products in different markets as long as you have different part numbers associated with them so traceability can be maintained.
Deadline extension note: In addition, it depends on what is changing; it’s possible some changes would not require a 510(k) in the U.S. based on the Deciding When to Submit a 510(k) flowcharts issued by FDA.
Smirthwaite: It is okay to have different products in different regulatory geographies.
Vanderbilt: It is acceptable and common to have different devices for EU and U.S. Traceability of both product and labeling is critical; many use an “-EU” and “-US” designation and put shipping controls in place in their inventory management systems.
Fenske: Are we past the time frame for this strategy if a company is seeking to maintain a product in the EU market under the MDR without interruption?
Dr. Bowness: Maybe. Revalidating production lines, stability, biocompatibility and other technical aspects associated with materials changes, plus the potential need to generate new clinical evidence, is very time consuming; the average timeframe for MDR conformity assessment is currently 13-18 months once accepted by a Notified Body. The new transition timelines provide for a longer period for the Notified Bodies to complete all the necessary transition reviews, but the backlog of legacy devices means timing remains critical and a queuing system is in place; the longer it takes for a manufacturer to submit the documentation for review, the greater the risk the transition period will end before they are re-certified. The first of the transition deadlines—May 2024—for the application itself is fast approaching. A surge in demand and applications is expected before this date, so again timing is critical.
Minor changes may not pose a substantial risk to the MDR transition, but anything more substantial, such as primary material or design changes may not be worth the risk to the transition timings. Careful consideration is necessary to avoid loss of market access at the end of the transition period.
Dr. Braddon: Potentially. This depends on the review cycle from the company’s specific Notified Body.
Brosseau: Given the limited bandwidth of Notified Body resources, I would recommend such companies reach out to their Notified Body to determine the timing of such a change. Additionally, when communicating potential changes to a Notified Body, a company should consider the prioritization of EU MDR review for legacy products and any new products or any products replacing legacy products. A holistic approach is necessary to ensure a smooth transition for all product families and to allow maximum utilization of the EU MDR transition extension.
Dr. Lauer: Yes, especially if testing is needed to ensure compliance. The testing labs are heavily booked and delays in scheduling can be 16 weeks or more.
Patel: MDR has extended their deadline multiple times now as the medical device industry is not quite ready to embrace all the changes, especially with the COVID impact but it’s not long until these extensions will stop. Currently MDR requirements regarding reusable devices have been extended to 2028 for now. UDI is not the only item reusable devices will be scrutinized under; there are many other factors that will need to be evaluated to market a reusable device in the EU once the MDR requirement deadlines are officially in place.
Pratt: You should have been thinking of this two years ago. An additional challenge is even finding regulatory consultants to help navigate changes and weigh the relative significance of them. In our case, some supply chain issues came up during COVID that forced our hand, but fortunately, we had time to mitigate them and incorporate the changes ahead of time. It doesn’t help that even simple communications with the regulatory bodies in a timely manner isn’t something you can count on anymore. You have to budget for the uncertainty and be prepared to bleed.
Dr. Räägel: Each product has its own timeline to transfer from MDD to MDR. I would recommend getting the Notified Body involved in this transition process as early as possible to make the remediation as smooth as possible and not end up in a time crunch when approaching the actual deadline.
Rollins: As has been said by others, each product is different. If your MDD registration is getting close to expiring, you might not have time to make changes and have them evaluated before you need to resubmit under MDR. If you have time, it’s a good time to look at changes.
Scifert: There is a pathway for changes that are not significant, but it is challenging, especially with the limited resources of the Notified Bodies. Many of these updates still require a change notification to be reviewed by the Notified Body and this can take quite a bit of time.
As an additional note, there is a proposal currently being presented to delay the EU MDR timeline out to 2027 for Class IIb and Class III devices and 2028 for Class I and Class IIa devices. Therefore, there is even more uncertainty at this time regarding the EU MDR transition.
Deadline extension note: Obviously this has now been implemented. It was necessary, but there are still challenges ahead. The transition to EU MDR will include product reviews that will continue to bog down the Notified Bodies and delay changes and/or new product submissions. All new products must be submitted to Notified Bodies under EU MDR. A great number of companies have made the decision to obsolete numerous product lines while some smaller companies have decided to pull out of Europe. We have a number of clients that are small startups and they are making the decision to start with U.S., then pursue an ISO 13485 and/or MDSAP certificate to get to other international markets. They are putting Europe as their lowest priority because of all these challenges, including time and cost.
Smirthwaite: The transition period has been extended. So, if a change is allowable, they have all that time to make it. The bigger question is whether it is allowable—most of them aren’t.
Vanderbilt: The answer to this question changes from month to month, which makes planning difficult. Agile companies are better able to respond to the moving target. For example, Switzerland voted to accept 510(k) clearance in lieu of CE marking. Other non-EU countries are considering doing the same.
One thing to add is that we’ve seen a few cases in which devices will be removed from the market because compliance is too expensive relative to how much revenue is generated from the product. This isn’t unexpected, but I’m curious to see how that will play out for small market “niche” devices.
Scifert: Bottom line is while the extension was absolutely necessary as the Notified Bodies could not review everything necessary prior to the original deadline, this also continues to put everything in a state of limbo for many more years, especially for new products.
That said, one of the concerns regarding the MDR—specifically, the fact that all devices must be recertified through a Notified Body to the new standard—could present an opportunity for some companies.
Since the product needs to be recertified anyway, does this open a window to making a design change? This question, along with several follow-ups, was posed to a number of industry representatives, many of whom are regulatory professionals aiding companies in their transition plans. Their feedback is shared in the following Q&A presentation.
(Author note: These questions were originally posed prior to the announcement of the deadline extension and participants were given an opportunity to update their responses following approval of the new MDR transition timeline. Some revised their comments, while others expanded on their response with a “deadline extension note,” as indicated in their response.)
Participants include:
- Peter Bowness, BSc, MPhil, Ph.D., vice president, Regulatory Affairs & Operations – Europe, MCRA
- Linda Braddon, Ph.D., CEO, Secure BioMed Evaluations
- Bryan Brosseau, president, Brosseau Consulting LLC
- Janelle (Jeni) Lauer, Ph.D., Biocompatibility Expert, Nelson Laboratories LLC
- Alpa N. Patel, B.S., RM(NRCM), director, Scientific Improvement, Nelson Laboratories LLC
- William Pratt, VP Operations and director of Creative Design, Kinamed Inc.
- Helin Räägel, Ph.D., Senior Biocompatibility Expert, Expert Advisory Services, Nelson Laboratories LLC
- Thor Rollins B.S. RM(NRCM), senior director of Toxicology and E&L Consulting, Nelson Labs LLC
- Christine Scifert, MS, MEM, partner, MRC Global
- Amie Smirthwaite, senior vice president, Intelligence and Innovation, RQM+
- Audrey Turley, B.S., director, Expert Advisory Services, Nelson Laboratories LLC
- Meredith Price Vanderbilt, MS, RAC, director of Consulting, Empirical Technologies Corp.
Dr. Peter Bowness: No. MDCG 2021-25 defines legacy devices as those devices, which, in accordance with Article 120(3) of the MDR, are placed on the market after the MDR’s date of application (DoA) until the end of the transition period if certain conditions are fulfilled. Those devices can be:
- Devices that are Class I under Directive 93/42/EEC (MDD), for which an EC declaration of conformity was drawn up prior to 26 May 2021 and for which the conformity assessment procedure under the MDR requires the involvement of a Notified Body.
- Devices covered by a valid EC certificate issued in accordance with Directive 90/385/EEC (AIMDD) or the MDD prior to 26 May 2021.
As such, for legacy devices and, in particular, if the device is subject to Article 54, it’s recommended not to make design or manufacturing changes prior to MDR certification; any changes could be made in the post-certification phase.
Deadline extension note: The recent MDR extension reinforces the transition provisions concerning changes under Article 120 but raises the prospect of legacy devices being stuck in their current configuration. As the medical device market consolidates under MDR, many components or devices are being removed or not transitioned to MDR, forcing other manufacturers to make fundamental changes to their devices. The extension, therefore, may not be useful for many manufacturers, so it remains recommended to complete the transition to MDR as quickly as possible.
Dr. Linda Braddon: In Secure BioMed Evaluations’ experience, any change not supported by an identical feature of a similar device in the EU market, clinical data may be needed for the change. This could be a great opportunity to incorporate changes but I would also recommend making the changed device a line extension to the original device in case there is an issue with the changes.
Bryan Brosseau: First, I will say the EU MDR has a lot of vague content and little clarifying guidance. Therefore, interpretation of EU MDR currently varies wildly between Notified Bodies. As such, I don't think one answer is suitable for all medical device manufacturers in the current climate. The requirements for technical documentation review has been raised significantly under EU MDR. By making a change at this time, previous data supporting the safety and performance of your device may be questioned if such a change is made. However, if the right supporting data and planning is in place, it might make sense to implement the change rather than wait a significant period of time for the Notified Body to schedule and then conduct the review of the change notification at a later date. The supporting data and planning might include the results of V&V (validation & verification) testing, technical justification for the applicability of previous data to the modified device, clinical evaluation, and PMCF (post-market clinical follow-up), and/or PMS plans, which monitor any impact in the real world on safety or performance from the change.
Dr. Janelle Lauer: In some cases, they may be forced to make a change (e.g., to remove a PVC containing DEHP) based on complying with updated CMR requirements. However, I doubt they would choose to make a change based solely on the recertification process (partly because of the FDA considerations referenced in my response to that question). In my experience, the supply chain remains the primary factor driving device changes, with design changes to improve functionality coming in second.
Alpa N. Patel: Yes. For reusable medical devices, it would be a good idea to add unique device identification (UDI) to the device as this is one of the required changes for reusable medical devices. Per MDR, “Devices that are reusable shall bear a UDI carrier on the device itself. The UDI carrier for reusable devices that require cleaning, disinfection, sterilization, or refurbishing between patient uses shall be permanent and readable after each process performed to make the device ready for the subsequent use throughout the intended lifetime of the device.” The reason for the UDI system is it allows for traceability of the devices in terms of use and reprocessing cycles, and can also help with the effectiveness of post-market surveillance.
William Pratt: Generally, I’d say if it’s a change you’ll do in the near term anyway, you might consider it. Otherwise, you’ll pay twice for the product review. The process still has to conform to the new standard, and that can be time and resource consuming depending on the type of change. Any change requiring testing and/or validation can have timeline implications that might be unacceptable if the focus is on staying in the market. The regulatory authorities are overwhelmed with this conversion, so keeping things straightforward is probably a good instinct to follow.
Dr. Helin Räägel: Since the MDR recertification would require the Notified Body to review all available data on the device, adding a change would just expand the biocompatibility assessment. Companies should form a good communication channel with their Notified Body to get them involved in the assessment. This has been a good strategy to promote a two-way conversation between the company and the Notified Body, allowing the evaluation process to be more effective and smoother.
Thor Rollins: It’s not only a great time to make changes but it’s a perfect time to examine the changes that have retroactively happened over the history of the product. Many times, small changes happen with a not-to-file justification on accepting the change. When a device has a long history of use, these small changes might build on each other to equal a dramatic change that should be considered for MDR.
Christine Scifert: It is difficult to change anything right now. The DOCs are currently locked for product under MDD requirements. There is a flowchart to determine if a significant change is being made, but you also need to discuss with your scheme manager/company representative from the Notified Body. There is some variability in responses at times.
Deadline extension note: This hasn’t changed, but now this time period is extended longer so changes to existing products and new products will be difficult to do until a company has approvals under EU MDR.
Amie Smirthwaite: The opportunity is fairly limited. Article 120(3) of the MDR says devices with a valid MDD or AIMDD certificate may continue to be placed on the market until the end of the transition period, providing there have been no significant changes to the design or intended purpose. MDCG 2020-3 has several flowcharts to enable a manufacturer to decide what is or isn’t significant. It would take a lot of text to talk through all the different scenarios, but essentially (with one exception that I can think of) if something would trigger an MDR review, it would not be allowable under an MDD certificate. The exception is design changes associated with corrective actions that have been assessed and accepted by the relevant Competent Authority. So, if you think a change to a device would be more difficult to get through MDR, it probably can’t be made on the MDD or AIMDD certificate. Any change to materials, coatings, or components for Class III devices would be considered significant. Reference to materials and coatings suggests we are talking about invasive devices, and any material change to an invasive device (even in Class IIa or IIb) is normally considered significant.
Audrey Turley: Yes, I would say this is a good time to incorporate a change. During MDR recertification, a full evaluation of the device must occur anyway so it is a good time to include any changes. Especially if additional testing is already on the table for the recertification.
Meredith Price Vanderbilt: For many changes, it is unlikely there is time to get a design change completed and validated, especially with the clinical review requirements. Additionally, if your design was already reviewed under MDD, adding changes might lengthen your MDR review time if you have the same reviewing agency as you did for MDD.
Fenske: If a client approached you with this question about one of their products, how would you advise them?
Dr. Bowness: I would recommend an MDR application based on changes that are limited only to those required to demonstrate conformity to the MDR (for example SSCP, implant cards, UDI, EUDAMED, etc.) and make any design changes post-certification to the MDR.
Dr. Braddon: Get recertification on the original device and either add modifications as a line extension or go back in after recertification. New features can create new questions that could slow the process.
Brosseau: Given the high degree of inconsistency between Notified Bodies and uncertainty with respect to review timelines and EU MDR interpretation, I would advise a risk/benefit evaluation to determine the timing for such a change notification. If the change isn't required urgently due to something like supply chain shortages or if the change doesn't promise a significant improvement in safety or performance, I would advise waiting until after all EU MDR transition elements are completed. And, if the addition of a change to the review might delay EU MDR certification and, therefore, prevent access to the EU market altogether for the product, I would refrain from including the change.
Patel: I would strongly advise them to implement a UDI system for their device that is directly placed on the device and not the packaging. In addition, I would recommend they perform validation studies to ensure the UDI will remain active and legible through the use life of the device, which is a requirement of the MDR.
Pratt: The client is responsible for their own cost/benefit analysis, and the cost risks could be significant, including loss of access to the market for a longer than expected time period. Supply chain risk has been substantial in recent years, and that might actually be a driving factor in considering a change—pro and con—but the regulatory risk is similarly substantial at this time.
Dr. Räägel: We would definitely recommend writing up a document that looks at all the available information and then defines whether additional risks exist that should be followed up with additional testing. As specified in ISO 10993-1, the recertification does not necessarily mean testing needs to be re-done; the purpose of this is to verify risks have been looked at and appropriate data exists to cover those risks. If a change is occurring, this would also be addressed using this risk-based approach; identifying what has changed and what the impact is to the final finished device.
Scifert: I would ask for details on what is changing and walk through the flowchart with them to provide some initial feedback. To me, the key is making sure you’re staying aligned with your scheme manager/company representative from the Notified Body.
Smirthwaite: It would depend on the device and why they wanted to make the change, but in most instances it probably wouldn’t be allowable; if it were allowable, it probably wouldn’t be that much of a challenge under MDR either.
Turley: For device changes during an MDR recertification, it is important to understand previously gathered data that will be used to support the recertification. Then the change should be assessed to further understand any potential risk to the patient posed by the change. These two parts should then be combined to understand what testing/risk assessment is needed.
Fenske: What factors would that client need to consider before making the decision to proceed?
Dr. Bowness: The extension to the transition timelines to 2027/2028 for MDD certified devices make this an ever more likely scenario for manufacturers. There are many factors that drive this decision. Even if equivalence is taken as the conformity pathway, there still must be sufficient clinical evidence on the device. The level of clinical evidence required by MDR is greater than under MDD and is subject to higher levels of scrutiny by the Notified Bodies and MDCG. Therefore, additional data generation may still be required, in which case, it may be the manufacturer needs to run a clinical investigation anyway, negating the need for equivalence, and can thus make changes prior to the investigation. Timing is also a consideration, as the new materials would require testing. If an investigation is ongoing, there may well be time to retest the materials and bring the technical documentation in line with the changes. If the manufacturer plans to make the changes post-MDR certification, a change review will be required; the change review itself would then add to the overall timeline of marketing the new device variant. Further, if the change is driven by a noted safety concern, non-conformity, unacceptable risk, changes in state-of-the-art, or unavailability of the original materials, the manufacturer may have no option but to implement the change as soon as possible. And of course, all of these activities are not cheap.
Dr. Braddon: An evaluation of the desired modifications should be critically approached. How will the modifications be supported in the Clinical Evaluation Report?
Brosseau: The necessary supporting data for the change (V&V testing, technical justification for the applicability of previous data to the modified device, clinical evaluation, etc.), the necessary activities in the post-market phase for the change (PMCF and/or PMS activities related to the change), and the potential impact on delay in certification.
Dr. Lauer: These considerations depend on the context of the device and situation, so it is difficult to make a meaningful comment without specific details. These discussions play out like a Choose-Your-Own-Adventure story—no two discussions follow the same path.
Patel: Unfortunately, the client does not have a choice as this is a required piece for all Class 1r (reusable) medical devices. This is a new classification MDR brought on for reusable medical devices.
Pratt: Any factor that goes into the product needs to be considered from a “what can go wrong” perspective. The status quo has risks in this regard, but the change process can have unforeseen issues, unless you (at least) trial run the scenario. Einstein was big on “mind experiments,” which would be called simulations in today’s parlance. We’re going to develop more skill in systems analysis in ways we haven’t had to in the past, with a focus on the human systems involved. The more international your market is, the more varied your considerations are going to be; every national regulatory agency is awakened to the possibilities of revenue generation, so the hoops to be jumped through are multiplying.
Rollins: What is the percentage of patient contacting surface area that has been impacted by the change? The more surface area, the larger the potential risk to the patient.
Scifert: Can the change be considered not significant and does it impact your critical suppliers? You cannot add part numbers at this time to products currently under MDD.
Smirthwaite: Whether or not the change could be made on an MDD or AIMDD certificate, based on the criteria in MDCG 2020-3.
Turley: There are several considerations. What is the reason for the change? Does it occur on a patient contacting component? Will the change require extensive testing to assess risk to the patient? Can previous data be used to support the change?
Vanderbilt: I would ask if (1) they really need the European market right now, and (2) are those changes critical to further distribution. The cost of CE marking and of design changes for a CE-marked device are high, and the timelines are painfully long.
Fenske: If a company did move forward with this strategy, would it be important for them to resubmit the product to the FDA so the same device (same BOM) is being sold within each market or is it ok to have different products within different markets/regions?
Dr. Bowness: This depends on the manufacturer’s production and supply processes and the factors mentioned previously. Dual manufacturing may not be an issue, especially if the new materials are more expensive.
Dr. Braddon: Any modification for FDA would need to go through the evaluation as to whether the change could be documented or would need a new 510(k). The question as to whether it is more efficient to have one SKU or multiple SKUs for different regions is a business decision on how to manage labeling during manufacturing. Sometimes, it is easier to have separate part numbers for different regions. Other times, it is easier to have a single part number that has a universal labeling approach. This is really a case-by-case decision.
Brosseau: I would advise the company consider this as part of their assessment to proceed with the change. Specifically, they should use FDA Guidance documents "Deciding When to Submit a 510(k) for a Change to an Existing Device" or "Modifications to Devices Subject to Premarket Approval (PMA) - The PMA Supplement Decision-Making Process" to assist in determining if change notification to the FDA is even required. If a change notification to FDA is required, determining if multiple SKUs is acceptable to the company from an operations perspective would be the next decision. I think we are generally headed toward splitting product codes for situations such as this, especially with the increased EU MDR requirements around information provided with devices.
Dr. Lauer: I doubt the companies want to have different devices in different markets and I know of no specific examples of this choice being made. Some minor changes will not trigger a full suite of tests in most markets, but a biological risk analysis would be needed to review the details of the device and proposed change(s) to determine which tests may be necessary.
Patel: Although the UDI is not a requirement for FDA, I can foresee this as a criteria FDA might look into in the future.
Pratt: Depending on the change, FDA might not require it. We already contend with localization for labelling, but a different product line in a material sense is a different product line; it’s an additional burden to maintain and it eats into the economies of scale. Again, cost/benefit has to be considered. Obviously staying in a market or not is the first big decision. Europe is getting cut out of many company’s plans; it’s not worth the expense or drain on resources. I wouldn’t be surprised if European companies drop some product lines out of their own market. It’s all about triage at this point.
Dr. Räägel: From a biocompatibility perspective, if a change is minimal and doesn’t affect the function or overall biocompatibility assessment, then for the FDA, a letter to file may be sufficient (without a new submission) if a device is already cleared for the U.S. market. Regardless, it is very important to keep good documentation on the assessments to ensure it is clear what has been changed and why it does not impact the final finished device. It should, however, be recognized that it’s ok to have different products marketed in different regions.
Rollins: The FDA does provide guidance on when to submit a new 510(k). If the change is minimal, you can follow that guidance and not resubmit. If not, a new 510(k) is needed.
Scifert: It is acceptable to have different products in different markets as long as you have different part numbers associated with them so traceability can be maintained.
Deadline extension note: In addition, it depends on what is changing; it’s possible some changes would not require a 510(k) in the U.S. based on the Deciding When to Submit a 510(k) flowcharts issued by FDA.
Smirthwaite: It is okay to have different products in different regulatory geographies.
Vanderbilt: It is acceptable and common to have different devices for EU and U.S. Traceability of both product and labeling is critical; many use an “-EU” and “-US” designation and put shipping controls in place in their inventory management systems.
Fenske: Are we past the time frame for this strategy if a company is seeking to maintain a product in the EU market under the MDR without interruption?
Dr. Bowness: Maybe. Revalidating production lines, stability, biocompatibility and other technical aspects associated with materials changes, plus the potential need to generate new clinical evidence, is very time consuming; the average timeframe for MDR conformity assessment is currently 13-18 months once accepted by a Notified Body. The new transition timelines provide for a longer period for the Notified Bodies to complete all the necessary transition reviews, but the backlog of legacy devices means timing remains critical and a queuing system is in place; the longer it takes for a manufacturer to submit the documentation for review, the greater the risk the transition period will end before they are re-certified. The first of the transition deadlines—May 2024—for the application itself is fast approaching. A surge in demand and applications is expected before this date, so again timing is critical.
Minor changes may not pose a substantial risk to the MDR transition, but anything more substantial, such as primary material or design changes may not be worth the risk to the transition timings. Careful consideration is necessary to avoid loss of market access at the end of the transition period.
Dr. Braddon: Potentially. This depends on the review cycle from the company’s specific Notified Body.
Brosseau: Given the limited bandwidth of Notified Body resources, I would recommend such companies reach out to their Notified Body to determine the timing of such a change. Additionally, when communicating potential changes to a Notified Body, a company should consider the prioritization of EU MDR review for legacy products and any new products or any products replacing legacy products. A holistic approach is necessary to ensure a smooth transition for all product families and to allow maximum utilization of the EU MDR transition extension.
Dr. Lauer: Yes, especially if testing is needed to ensure compliance. The testing labs are heavily booked and delays in scheduling can be 16 weeks or more.
Patel: MDR has extended their deadline multiple times now as the medical device industry is not quite ready to embrace all the changes, especially with the COVID impact but it’s not long until these extensions will stop. Currently MDR requirements regarding reusable devices have been extended to 2028 for now. UDI is not the only item reusable devices will be scrutinized under; there are many other factors that will need to be evaluated to market a reusable device in the EU once the MDR requirement deadlines are officially in place.
Pratt: You should have been thinking of this two years ago. An additional challenge is even finding regulatory consultants to help navigate changes and weigh the relative significance of them. In our case, some supply chain issues came up during COVID that forced our hand, but fortunately, we had time to mitigate them and incorporate the changes ahead of time. It doesn’t help that even simple communications with the regulatory bodies in a timely manner isn’t something you can count on anymore. You have to budget for the uncertainty and be prepared to bleed.
Dr. Räägel: Each product has its own timeline to transfer from MDD to MDR. I would recommend getting the Notified Body involved in this transition process as early as possible to make the remediation as smooth as possible and not end up in a time crunch when approaching the actual deadline.
Rollins: As has been said by others, each product is different. If your MDD registration is getting close to expiring, you might not have time to make changes and have them evaluated before you need to resubmit under MDR. If you have time, it’s a good time to look at changes.
Scifert: There is a pathway for changes that are not significant, but it is challenging, especially with the limited resources of the Notified Bodies. Many of these updates still require a change notification to be reviewed by the Notified Body and this can take quite a bit of time.
As an additional note, there is a proposal currently being presented to delay the EU MDR timeline out to 2027 for Class IIb and Class III devices and 2028 for Class I and Class IIa devices. Therefore, there is even more uncertainty at this time regarding the EU MDR transition.
Deadline extension note: Obviously this has now been implemented. It was necessary, but there are still challenges ahead. The transition to EU MDR will include product reviews that will continue to bog down the Notified Bodies and delay changes and/or new product submissions. All new products must be submitted to Notified Bodies under EU MDR. A great number of companies have made the decision to obsolete numerous product lines while some smaller companies have decided to pull out of Europe. We have a number of clients that are small startups and they are making the decision to start with U.S., then pursue an ISO 13485 and/or MDSAP certificate to get to other international markets. They are putting Europe as their lowest priority because of all these challenges, including time and cost.
Smirthwaite: The transition period has been extended. So, if a change is allowable, they have all that time to make it. The bigger question is whether it is allowable—most of them aren’t.
Vanderbilt: The answer to this question changes from month to month, which makes planning difficult. Agile companies are better able to respond to the moving target. For example, Switzerland voted to accept 510(k) clearance in lieu of CE marking. Other non-EU countries are considering doing the same.
Additional Comments Made After the Deadline Extension
Dr. Lauer: The lab delays have come down a bit and tests are generally back to normal turnaround times, so that’s not such a significant issue any longer. We’re seeing fewer requests for biocompatibility documents related to this change. There are quite a few MDR-related projects in the pipeline, but the relaxed implementation times for these requirements have made compliance more manageable.One thing to add is that we’ve seen a few cases in which devices will be removed from the market because compliance is too expensive relative to how much revenue is generated from the product. This isn’t unexpected, but I’m curious to see how that will play out for small market “niche” devices.
Scifert: Bottom line is while the extension was absolutely necessary as the Notified Bodies could not review everything necessary prior to the original deadline, this also continues to put everything in a state of limbo for many more years, especially for new products.