ARTICLE SUMMARY:
Healthcare agencies the world over have ramped up emergency efforts as large swaths of society go into a literal standstill. But what is the impact on these agencies’ day-to-day public health missions, including oversight of devices not directly tied to the pandemic response? A roundup of regulatory impacts for the EU MDR, FDA, and Brazil’s ANVISA, in this rapidly evolving situation.
The rightful emphasis of regulators right now is responding to the COVID-19 emergency with policies that expedite emergency diagnostics, equipment, and therapies to the market, while monitoring serious supply chain shortages. But the broader public health mission of governments, beyond coronavirus response, remains, and that includes oversight of clinical trials and new medical technologies. How are those activities being impacted so far under this global health emergency? Here are brief snapshots of this rapidly evolving situation from Europe, the US, and Brazil.
MDR Prep Accelerates in the Face of Moratorium Demands
The situation was anything but business as usual in Europe before the pandemic hit. The transition to the EU Medical Device Regulation (MDR) is slated for May 26, and many in industry have been questioning for some time whether the system will be ready to make the jump.
With coronavirus halting travel and face-to-face contact, the ability of notified bodies to do their jobs in auditing device companies is severely restrained. Transitioning to the new, more stringent MDR was already a lot to handle, and industry has argued the lack of designated notified bodies and clear guidance was enough to support an MDR delay. The pandemic potentially sends whatever semblance of readiness that was in place into disarray.
“If you have an audit scheduled within the next few weeks, as part of getting ready for MDR, it is more than likely it will not happen,” affirms Ibim Tariah, VP of MDR/IVDR services for R&Q Solutions. “Companies will struggle to meet some of these deadlines.”
BVMed, the German medical device industry association, came out with a strong statement March 13 demanding a moratorium on the MDR until the coronavirus subsides.
"First notified bodies close or are limited in their work. Experts and auditors are no longer allowed to travel. Authorities are affected. Production facilities are affected. Suppliers are breaking away. And in addition to the known problems: too few notified bodies, too few experts, missing Legal acts and guidelines. The double-hit medtech industry now needs an MDR moratorium,” BVMed CEO Dr. Marc-Pierre Möll stated.
On top of such demands and in parallel with emergency efforts to conserve supplies of personal protective equipment, the EU government seems to be going the other direction on MDR. The MDR policy-making body, the Medical Device Coordination Group (MDCG), met (virtually) March 11-12 and followed that up with the rapid rollout of important documents necessary for the implementation of MDR.
Notably, as the meeting was going on, MDCG issued a “Joint implementation/Preparedness Plan” that made no mention of COVID-19. It addressed the pre-pandemic urgent needs for more notified bodies, documents, and the like. Then, this week, the EU group has so far rolled out five highly awaited guidance documents addressing:
- How to define “significant change” when a company is determining whether a device can continue to enjoy the MDR grace period (See “Modifications in the MDR Era: The Ambiguities of ‘Significant Change,”Market Pathways, October 7, 2019);
- Clinical/performance evaluation of software;
- Transitional provisions for Class I devices;
- Newly mandated “implant cards” that must be provided to patients; and
- Unique Device Identification, including the “Basic UDI-DI” for identifying device groups and making changes to individual UDI-DIs.
Meanwhile, notified bodies confirmed challenges they are facing both in carrying out responsibilities under the current Medical Device Directives, and transitioning to the new regulations.
“Notified bodies are in communication with their designating authorities to share contingency plans to deal with this extraordinary circumstance especially in areas affected by COVID-19,” TEAM-NB, the EU notified body industry association, said March 12.
Ultimately, an official delay to MDR would require agreement by the European Parliament and Council, which are the legislative bodies for the EU, and it is not clear that they are ready to do that. “We need the politicians to help in this process,” R&Q’s Tariah said.
EU policymakers may be noting the fact that they face challenges and are going to have to grant leeway to ensure medical device access whether the directives remain in effect or MDR begins to apply, so they might as well move forward with MDR.
The one challenge to that approach is that a joint on-site audit is required of all notified bodies seeking designation to operate under the new regulation, which is not possible under travel restrictions. However, according to a March 18 notified body “State of Play” document from the EU government, 41 of the 44 bodies that have applied for MDR designation have already undergone on-site audits, meaning it may be possible for more bodies to be designated during the current emergency.
But facts on the ground are changing daily, and it remains unknown what additional oversight functions may need to be sidelined as the outbreak grows in each country.
“My advice to manufacturers will be ..plan on with the date of application remaining May 26, 2020, but be aware of the changing dynamics,” Tariah said. “This situation is very fluid. Who knows? An announcement could be made any day. Or maybe not.”
FDA Reviews Move Ahead, But Social Distancing Has Impacts
Across the ocean in the US, FDA has gone into overdrive in addressing, in particular, diagnostics testing capacity for COVID-19 with frequently updated policies and Emergency Use Authorizations. It’s also focused on major supply chain challenges for tests, personal protective equipment, and other products.
For other products, though, there are no signs as of yet that review processes are being derailed, several regulatory consultants who work closely with the agency on behalf of industry clients told Market Pathways.
There are “no indications of delays on FDA's part to date,” Sheila Hemeon-Heyer, founder and president of Heyer Regulatory Solutions noted in a March 17 email. “Most reviewers are used to/set up for work at home.”
Aaron Josephson, senior director at ML Strategies, agrees, noting on the MassMEDIC call that he does not see signs that MDUFA review deadlines will slip in any major way. “I have not heard anything makes me think that they are not still committed to meeting those goals,” he said.
“I think the best thing to do is stay in touch with your review team at FDA,” Josephson recommended. “These folks are still working. There may be some delays…because they are not in their normal work environment.” But, he emphasized, “I have not seen anything to suggest that the basic business of FDA is halting.”
Nonetheless, the sudden halt on traveling and limitations on face-to-face interactions is having some impact. FDA has publicly postponed all foreign facility inspections, and some domestic facility inspections are also likely being canceled, consultants say. That could slow down the approval process for PMAs that require pre-approval inspections.
“If those GMP inspections are required and the application (PMA) is approaching a MDUFA goal, there is a likelihood that an approvable pending GMP letter will be issued,” noted Christy Foreman, a senior consultant with Biologics Consulting, on March 17. “That isn’t a great place for a company to be. The user fee goal has been met–so there is a higher likelihood that this becomes a lower priority.”
In addition, advisory panel meetings are being pushed back. FDA, for instance, postponed its scheduled April 16 Circulatory Systems Devices Panel meeting, which was set to consider the PMA for Andover, MA-based TransMedics Inc.’s TransMedics Organ Care System (OCS)—Heart, a preservation and assessment system for donated hearts. A delayed advisory panel can be particularly challenging for smaller companies, Foreman noted.
Ultimately, FDA may be able to hold some advisory panels and other important meetings virtually. The agency says it is exploring whether its planned April 7 public forum to kick off discussions for the 2022 reauthorization of device user fees can be held by webcast only.
When it comes to pre-market submissions, home-based work could potentially cause a challenge, since the applications (eCopies on CDs or other drives) often must come through by mail. But stakeholders say the agency has designated a limited staff to be onsite to load eCopies into FDA’s electronic system so reviewers can access them remotely. (And FDA is being more flexible about how it is receiving COVID-19-related emergency use authorization applications.)
Further back in the development process, FDA-regulated clinical trials might also be facing delays. For one, Bioresearch Monitoring (BIMO) inspections are reportedly being cancelled. That could slow down PMA and investigational device exemption (IDE) processes. In addition, getting study-enrolled patients to show up for visits is a challenge right now.
“That will become an out-of-window visit or missing data point, which is not a good thing for clinical studies,” Foreman said. “Some clients are looking at trying to schedule visits using telehealth options.”
On March 18, FDA Issued a guidance document making the recommendation to use telehealth and outlining considerations “to assist sponsors in assuring the safety of trial participants, maintaining compliance with good clinical practice, and minimizing risks to trial integrity.”
Brazil GMP Contingencies
Brazil’s ANVISA regulatory agency, meanwhile, has issued a specific plan for how it will handle required GMP audit requirements for product filings in the country. For submissions received prior to its March 13-released resolution (in Portuguese), the agency says it will apply “extraordinary” procedures, including remote health inspections via video conferencing and digital tools and use of information from foreign regulatory authorities, to grant temporary certifications. Once ANVISA sunsets the emergency resolution, companies will need to seek longer-term certification through the conventional inspection process.
ANVISA makes clear that these procedures are reserved for items that have already been filed, not to newly submitted petitions. The exception, of course, is for devices and drugs that specially address COVID-19 needs. The agency has made it clear that it is prioritizing assessment of COVID-19 diagnostics.
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