Michael Barbella , Managing Editor11.10.21
It’s been a long, mad dash to the finish line these past few years, but it’s finally over.
The race has ended, the victory laps complete.
The track is empty.
Time to focus on the next race, the countdown for which has already begun.
With the MDR sprint mercifully behind them, medtech organizations must now turn their attention to the next leg of Europe’s revamped regulatory relay: the IVDR.
The global MDR run officially ended on May 26, a year later than originally planned, courtesy of the COVID-19 pandemic. The additional time was both a boon and bane for the industry, helping countless companies meet the new deadline but failing to resolve significant challenges with the regulations’ implementation.
“No matter where you’re standing, the MDR ship has sailed....the date of MDR application has come, it is the only pathway in Europe now for certifying medical devices,” Oliver Bisazza, director, Regulations & Industrial Policy, MedTech Europe, told a MedTech Conference panel earlier this fall. “We really are now in MDR chapter two. The ship has sailed and we need to keep it afloat. I don’t think that ship is necessarily going to sink tomorrow, I think it is sailing, but we are keeping our eyes on a number of things to assess whether that ship is going to stay healthily afloat in the years and decades to come.”
Buoyancy maintenance, in fact, will largely depend on completion of the MDR’s basic infrastructure. The ship left port this past spring without enough Competent Authorities (CA) and Notified Bodies (NB) crew, which have made it challenging to certify both combination products and new, innovative medical devices in a timely manner.
“There have been 22 Notified Bodies designated so far for the MDR, and that means some companies may not find any suitable Notified Body available after a certain time,” noted Michel Marboeuf, Stryker Corp.’s senior director, Regulatory Affairs Corporate. “Moving from one Notified Body to another might not be possible, and some Notified Bodies have been designated for a limited scope. Everyone needs to go through this process and basically, the supply is not matching the demand. Some Notified Bodies do not have the necessary expertise or capacity to respond or review submissions. This is definitely one of the challenges of the system.”
Another challenge aboard the S.S. MDR is the lack of rule harmonization and definitive agreements/mandates between the EU and other countries, particularly Switzerland, a key medical device supplier to the continent. Also complicating shipboard life is the unpredictable recognition of international MDR certifications.
Resolving these challenges is critical to ensuring the MDR ship remains afloat and capable of fostering product innovation under the new rules, industry watchdogs claim. Viable solutions also will help the medtech sector avoid potential device shortages, though regulatory officials expect some products to be lost in the proverbial shuffle.
“I think it’s important to know that there are challenges and it’s hard to come up over the new barrier, but I have to remind all that there is a reason [for] the new rules,” Thomas Wejs Moller, chair of Competent Authorities for Medical Devices at the Danish Medicines Agency, reminded his fellow MedTech Conference panelists. “We needed the new rules. The rules we had were more than 20-25 years old, and with the [medical device] development we’ve seen we needed to strengthen the whole thing a little bit. I think it’s important to acknowledge that it’s needed to lift the whole area up to a new level. There will be consequences for companies maybe in terms of some market adjustments—it’s a little hard to say, really. We can do our best to make it as smooth as possible but there will always be products that will not come into the new system because, well, there is a reason why it’s been lifted a little bit.”
Understandably so, but medtech executives are concerned the reasoning will disproportionately impact legacy products, orphan medical devices, and new technologies that lack ample clinical evidence to support their efficacy. The new regulations also could possibly price numerous small and medium-sized device firms out of the market, as these organizations anticipate sacrificing a sizable portion of their profits on MDR certification.
Precise cost estimates for the certification process are difficult to calculate because the system’s basic infrastructure is still in flux. However, most medtech companies (44 percent) expect to devote between 1 percent and 5 percent of their annual revenue toward MDR compliance, a Climedo Health survey concluded earlier this spring. Nearly one-third (31 percent) anticipate a higher price tag (between 5 percent and 10 percent of their annual revenue), and 13 percent of poll respondents fear spending more than 10 percent of their profits on MDR credentialing.
“In general, the MDR ship is sailing. But there are two things I see as a consultant,” noted Bernhard Bichsel, senior consultant at ISS AG, Integrated Science Services, a Swiss consultancy providing embedded software development, regulatory, and clinical evaluation report writing support to medical device companies. “One, it’s slowing down innovation. We are helping startup companies and usually they don’t make it to market or they start with the U.S. first. This is especially true for software companies. The second thing, which bothers me a little bit as a citizen, is the issue of [potential] shortages. I have manufacturers that I’m helping to reduce their product portfolio. Because of the new regulations, it’s just too expensive to scale all their products up to the new requirements, so I focus on the blockbusters. The orphan medical devices are especially at risk, at least some element of them, anyway. I think people will see these disturbances in the market in the future.”
In the very near future, actually: Monumental disturbances are looming next spring for the in-vitro diagnostics sector, which lacks the capacity to process the tidal wave of tests needing new (or renewed) NB certificates under Europe’s latest IVD Regulation (IVDR).
A MedTech Europe report estimates that 78 percent of diagnostics currently on the market will require a certificate, compared to only 8 percent under the previous (existing) mandate (IVDD). Manufacturers are hoping to transition up to 31,118 IVDs to the new regulation, compared with 39,844 diagnostics under the present rule, leaving a 22 percent potential shortfall in available devices, the report states.
That shortfall, according to regulatory officials, is directly attributable to the severe dearth of designated Notified Bodies. The IVDR Notified Bodies pool is in worse shape than its medical device counterpart, with just six NBs commissioned thus far for diagnostics, most of which were designated over the summer.
“We are now only less than nine months before the date of application—a hard stop for the majority of IVDs with no grace period or (for practical reasons) sell-off provision to rely on,” states MedTech Europe’s report, dated Sept. 8 (and co-authored by Bisazza). “...much time and effort is still needed to ensure that EU IVD medical tests do not fall off a cliff-edge. The lack of IVDR infrastructure is the main reason stated for this expected and avoidable loss. In the early days of the new regulation, it had seemed possible to create Notified Body capacity, the guidance, and other infrastructure, but with the imminent date of application, there is no longer enough time.”
A growing chorus of healthcare professionals agree, and have called upon the European Medicines Agency to delay the IVDR’s implementation, slated for May 26, 2022. A deferral, several trade groups and companies contend, is the only way to prevent serious patient care disruptions, particularly amongst those undergoing targeted cancer treatment.
Extra time also would provide cancer patients with uninterrupted access to biomarker testing, enabling up to 65,000 non-small cell lung and ovarian cancer patients annually to receive the testing needed to undergo targeted therapy for their diseases.
“We need to postpone the IVDR. The system itself is not ready,” Bichsel said. “It’s either going to force manufacturers into a gray zone, or force products out of the market, which could have bad effects on patients. There are a number of ways to save it, but if you don’t change anything we will not be ready at the time [of application]. The Notified Bodies capacity is the problem.”
Indeed, NB deficiency is a problem, but it’s not the only defect in the IVDR’s hull. Other structural weaknesses rest with EUDAMED, expert panels, EU reference labs, and (inadequate) guidance, though none are as efficient as the latter in breeding inconsistent decision-making amongst manufacturers, NBs, and Competent Authorities. MedTech Europe’s report cites several key areas of missing guidance, including performance evaluations, OEM products, Class D scrutiny, companion diagnostics, and clinical trial assays (clarity is needed on precisely which tests used in new drug trials will be subject to IVDR mandates).
Realizing such an ill-equipped ship would endanger its passengers (and crew), the European Commission in mid-October proposed a progressive rollout of the IVDR to avoid product shortages. Next May’s date still applies to CE-marked devices with no NB involvement or “new” products lacking an NB certificate or declaration of conformity, but higher-risk Class C and D diagnostics (HIV, hepatitus, influenza tests) must be fully compliant by May 2025 and 2026, respectively. Lower-risk Class A and B sterile devices, meanwhile, must transition to the new rules by May 2027.
“The COVID-19 pandemic has shown how essential it is to have accurate diagnostics and a robust regulatory framework for in-vitro medical devices,” Stella Kyriakides, Health and Food Safety Commissioner, said in an Oct. 14 prepared statement. “Shortages at this point in time are unthinkable. The pandemic has imposed unprecedented challenges also for our medical devices industry. With more time to prepare for the application of the EU new rules, we will ensure there is a continuous supply of essential in-vitro diagnostic medical devices on the market, while not compromising on safety. I call on all manufacturers to prepare for certification under the new Regulation as soon as possible and not wait until the end of the transition period.”
Moller, however, opposes a delay, contending the new regulations are imperative to better patient care.
“Why is the IVDR coming into place? Because it is a very underregulated area in Europe,” he said. “Being a Competent Authority during the COVID-19 crisis, and being in charge of antigen tests and PCR tests in Denmark over the last year and a half, I can tell you the things we saw coming in for professional use with a CE mark from all over the world—the quality was not necessarily there. This is an area where we all need to be better—as taxpayers, as patients, and as citizens. I think we would all prefer [diagnostics] to be better. That being said, I know there are challenges here. But I think it’s important to get the IVDR ship sailing and get the destination port locked in so the ship knows where it’s sailing and that clarity, or direction is there. That’s the best thing that can happen for all of us.”
Apart from a deadline extension, of course.
Be sure to review the other portions of the 2021 Year in Review feature:
Ransomware Attacks Push Cybersecurity into the Spotlight
Supply Chain Struggles for Medtech Manufacturers
M&A Accelerates During the Pandemic
The race has ended, the victory laps complete.
The track is empty.
Time to focus on the next race, the countdown for which has already begun.
With the MDR sprint mercifully behind them, medtech organizations must now turn their attention to the next leg of Europe’s revamped regulatory relay: the IVDR.
The global MDR run officially ended on May 26, a year later than originally planned, courtesy of the COVID-19 pandemic. The additional time was both a boon and bane for the industry, helping countless companies meet the new deadline but failing to resolve significant challenges with the regulations’ implementation.
“No matter where you’re standing, the MDR ship has sailed....the date of MDR application has come, it is the only pathway in Europe now for certifying medical devices,” Oliver Bisazza, director, Regulations & Industrial Policy, MedTech Europe, told a MedTech Conference panel earlier this fall. “We really are now in MDR chapter two. The ship has sailed and we need to keep it afloat. I don’t think that ship is necessarily going to sink tomorrow, I think it is sailing, but we are keeping our eyes on a number of things to assess whether that ship is going to stay healthily afloat in the years and decades to come.”
Buoyancy maintenance, in fact, will largely depend on completion of the MDR’s basic infrastructure. The ship left port this past spring without enough Competent Authorities (CA) and Notified Bodies (NB) crew, which have made it challenging to certify both combination products and new, innovative medical devices in a timely manner.
“There have been 22 Notified Bodies designated so far for the MDR, and that means some companies may not find any suitable Notified Body available after a certain time,” noted Michel Marboeuf, Stryker Corp.’s senior director, Regulatory Affairs Corporate. “Moving from one Notified Body to another might not be possible, and some Notified Bodies have been designated for a limited scope. Everyone needs to go through this process and basically, the supply is not matching the demand. Some Notified Bodies do not have the necessary expertise or capacity to respond or review submissions. This is definitely one of the challenges of the system.”
Another challenge aboard the S.S. MDR is the lack of rule harmonization and definitive agreements/mandates between the EU and other countries, particularly Switzerland, a key medical device supplier to the continent. Also complicating shipboard life is the unpredictable recognition of international MDR certifications.
Resolving these challenges is critical to ensuring the MDR ship remains afloat and capable of fostering product innovation under the new rules, industry watchdogs claim. Viable solutions also will help the medtech sector avoid potential device shortages, though regulatory officials expect some products to be lost in the proverbial shuffle.
“I think it’s important to know that there are challenges and it’s hard to come up over the new barrier, but I have to remind all that there is a reason [for] the new rules,” Thomas Wejs Moller, chair of Competent Authorities for Medical Devices at the Danish Medicines Agency, reminded his fellow MedTech Conference panelists. “We needed the new rules. The rules we had were more than 20-25 years old, and with the [medical device] development we’ve seen we needed to strengthen the whole thing a little bit. I think it’s important to acknowledge that it’s needed to lift the whole area up to a new level. There will be consequences for companies maybe in terms of some market adjustments—it’s a little hard to say, really. We can do our best to make it as smooth as possible but there will always be products that will not come into the new system because, well, there is a reason why it’s been lifted a little bit.”
Understandably so, but medtech executives are concerned the reasoning will disproportionately impact legacy products, orphan medical devices, and new technologies that lack ample clinical evidence to support their efficacy. The new regulations also could possibly price numerous small and medium-sized device firms out of the market, as these organizations anticipate sacrificing a sizable portion of their profits on MDR certification.
Precise cost estimates for the certification process are difficult to calculate because the system’s basic infrastructure is still in flux. However, most medtech companies (44 percent) expect to devote between 1 percent and 5 percent of their annual revenue toward MDR compliance, a Climedo Health survey concluded earlier this spring. Nearly one-third (31 percent) anticipate a higher price tag (between 5 percent and 10 percent of their annual revenue), and 13 percent of poll respondents fear spending more than 10 percent of their profits on MDR credentialing.
“In general, the MDR ship is sailing. But there are two things I see as a consultant,” noted Bernhard Bichsel, senior consultant at ISS AG, Integrated Science Services, a Swiss consultancy providing embedded software development, regulatory, and clinical evaluation report writing support to medical device companies. “One, it’s slowing down innovation. We are helping startup companies and usually they don’t make it to market or they start with the U.S. first. This is especially true for software companies. The second thing, which bothers me a little bit as a citizen, is the issue of [potential] shortages. I have manufacturers that I’m helping to reduce their product portfolio. Because of the new regulations, it’s just too expensive to scale all their products up to the new requirements, so I focus on the blockbusters. The orphan medical devices are especially at risk, at least some element of them, anyway. I think people will see these disturbances in the market in the future.”
In the very near future, actually: Monumental disturbances are looming next spring for the in-vitro diagnostics sector, which lacks the capacity to process the tidal wave of tests needing new (or renewed) NB certificates under Europe’s latest IVD Regulation (IVDR).
A MedTech Europe report estimates that 78 percent of diagnostics currently on the market will require a certificate, compared to only 8 percent under the previous (existing) mandate (IVDD). Manufacturers are hoping to transition up to 31,118 IVDs to the new regulation, compared with 39,844 diagnostics under the present rule, leaving a 22 percent potential shortfall in available devices, the report states.
That shortfall, according to regulatory officials, is directly attributable to the severe dearth of designated Notified Bodies. The IVDR Notified Bodies pool is in worse shape than its medical device counterpart, with just six NBs commissioned thus far for diagnostics, most of which were designated over the summer.
“We are now only less than nine months before the date of application—a hard stop for the majority of IVDs with no grace period or (for practical reasons) sell-off provision to rely on,” states MedTech Europe’s report, dated Sept. 8 (and co-authored by Bisazza). “...much time and effort is still needed to ensure that EU IVD medical tests do not fall off a cliff-edge. The lack of IVDR infrastructure is the main reason stated for this expected and avoidable loss. In the early days of the new regulation, it had seemed possible to create Notified Body capacity, the guidance, and other infrastructure, but with the imminent date of application, there is no longer enough time.”
A growing chorus of healthcare professionals agree, and have called upon the European Medicines Agency to delay the IVDR’s implementation, slated for May 26, 2022. A deferral, several trade groups and companies contend, is the only way to prevent serious patient care disruptions, particularly amongst those undergoing targeted cancer treatment.
Extra time also would provide cancer patients with uninterrupted access to biomarker testing, enabling up to 65,000 non-small cell lung and ovarian cancer patients annually to receive the testing needed to undergo targeted therapy for their diseases.
“We need to postpone the IVDR. The system itself is not ready,” Bichsel said. “It’s either going to force manufacturers into a gray zone, or force products out of the market, which could have bad effects on patients. There are a number of ways to save it, but if you don’t change anything we will not be ready at the time [of application]. The Notified Bodies capacity is the problem.”
Indeed, NB deficiency is a problem, but it’s not the only defect in the IVDR’s hull. Other structural weaknesses rest with EUDAMED, expert panels, EU reference labs, and (inadequate) guidance, though none are as efficient as the latter in breeding inconsistent decision-making amongst manufacturers, NBs, and Competent Authorities. MedTech Europe’s report cites several key areas of missing guidance, including performance evaluations, OEM products, Class D scrutiny, companion diagnostics, and clinical trial assays (clarity is needed on precisely which tests used in new drug trials will be subject to IVDR mandates).
Realizing such an ill-equipped ship would endanger its passengers (and crew), the European Commission in mid-October proposed a progressive rollout of the IVDR to avoid product shortages. Next May’s date still applies to CE-marked devices with no NB involvement or “new” products lacking an NB certificate or declaration of conformity, but higher-risk Class C and D diagnostics (HIV, hepatitus, influenza tests) must be fully compliant by May 2025 and 2026, respectively. Lower-risk Class A and B sterile devices, meanwhile, must transition to the new rules by May 2027.
“The COVID-19 pandemic has shown how essential it is to have accurate diagnostics and a robust regulatory framework for in-vitro medical devices,” Stella Kyriakides, Health and Food Safety Commissioner, said in an Oct. 14 prepared statement. “Shortages at this point in time are unthinkable. The pandemic has imposed unprecedented challenges also for our medical devices industry. With more time to prepare for the application of the EU new rules, we will ensure there is a continuous supply of essential in-vitro diagnostic medical devices on the market, while not compromising on safety. I call on all manufacturers to prepare for certification under the new Regulation as soon as possible and not wait until the end of the transition period.”
Moller, however, opposes a delay, contending the new regulations are imperative to better patient care.
“Why is the IVDR coming into place? Because it is a very underregulated area in Europe,” he said. “Being a Competent Authority during the COVID-19 crisis, and being in charge of antigen tests and PCR tests in Denmark over the last year and a half, I can tell you the things we saw coming in for professional use with a CE mark from all over the world—the quality was not necessarily there. This is an area where we all need to be better—as taxpayers, as patients, and as citizens. I think we would all prefer [diagnostics] to be better. That being said, I know there are challenges here. But I think it’s important to get the IVDR ship sailing and get the destination port locked in so the ship knows where it’s sailing and that clarity, or direction is there. That’s the best thing that can happen for all of us.”
Apart from a deadline extension, of course.
Be sure to review the other portions of the 2021 Year in Review feature:
Ransomware Attacks Push Cybersecurity into the Spotlight
Supply Chain Struggles for Medtech Manufacturers
M&A Accelerates During the Pandemic
