EU Overhaul, FDA Real-World Evidence Shift, and More Updates in End-of-Year Global Policy Bonanza

Editor’s notes: Pathways Picks’ will not be published on December 24 and 31. Look out for the next edition on January 7. Happy New Year!

EU Unveils MDR and IVDR Overhaul

Across-the-board streamlining proposed:

 The European Commission unveiled its highly anticipated legislative proposal to simplify the Medical Device and IVD Regulations December 16. The package did not disappoint, forwarding an abundance of legal changes targeted at reducing regulatory burdens for device firms, particularly small manufacturers. “A quick scan immediately reveals the inclusiveness of the revision can categorize it as a major overhaul, truly MDR 2.0 and IVDR 2.0,” said Gert Bos, a longtime medical device and notified body expert in the EU.

Here are some of the most significant provisions, among the larger list of proposed reforms:

More options to satisfy MDR/IVDR data requirements. What qualifies as “clinical data” to support conformity assessments would be more flexible, including clearer acceptance of real-world data. In addition, manufacturers would have more flexibility to rely on data from “equivalent” devices already on the market. Further, the proposal would allow more routine acceptance of non-clinical and in silico data.

Conformity assessment reined in. The new rules would restrain notified body conformity assessment for low and medium-risk devices (MDR Class IIa/b; IVDR Class B/C), requiring technical documentation assessment of only one representative devices for a generic device group—potentially covering an entire category or portfolio of a company’s products.

No recertification mandate. The plan would remove the current five-year recertification mandate for all devices, instead tasking notified bodies with risk-based periodic reviews of marketed products.

Predetermined change. It would formally introduce Predetermined Change Control Plans as a mechanism for device modifications into EU law and it would require notified bodies to inform manufacturers upfront what changes require approval or notification.

Breakthrough path. The package would establish an official designation for breakthrough devices, as well as orphan devices, and grant them access to “priority and rolling review” by notified bodies. The European Commission is also moving forward with a preliminary Breakthrough pilot path in advance of legislation, signaled with the release of a guidance document this week (see “Shorter-term measures,” below).

Structured dialogue. It would also provide a formal legal basis for substantive interactions between manufacturers and notified bodies, pre- and post-submission.

Fee reductions. Notified body fees would be reduced for small companies and orphan devices and the Commission would be “empowered to set, level, and structure” fees.

Centralizing governance. Several provisions would more tightly coordinate notified bodies (via NBCG-Med) and national competent authorities (via the European Medicines Agency).

Software classification. The Commission proposes to rework how software is risk-classified under the MDR, setting low-risk Class I as the default, but defining circumstances when it could be Class IIa, IIb, or III based the condition being addressed and the software’s role to “drive” or “inform” clinical management.

Less AI Act burden. Buried in the proposal is a provision that could significantly reduce the anticipated extra requirements from the EU AI Act. Currently, devices and IVDs must comply with all relevant AI Act requirements for high-risk systems in addition to MDR/IVDR rules. But a switch proposed in this week’s reform package would put them in a different category, subjecting AI devices and IVDs only to “selected provisions” of the AI Act to be later determined by the Commission. This goes even beyond AI Act reforms proposed in last month’s EU Digital Omnibus proposals.

Legislative debate is next. The plans will be submitted soon for consideration by EU lawmakers, i.e., the European Parliament and Council, so it is not yet clear if all elements of the proposal will become law and when the reforms will be enacted. “This revision is a long-awaited and necessary step to fix parts of the EU regulatory system that are clearly not working for patients, innovators and healthcare providers,” said Oliver Bisazza, CEO of MedTech Europe. “The task now for the European Parliament and the Council is to fully seize this opportunity in the final legislation.”

Shorter-term measures. The Commission, however, will not be waiting on lawmakers for two priority areas: breakthrough devices and rules to standardize notified body procedures:

Breakthrough pilot coming. The Medical Device Coordination Group mapped out a streamlined market pathway for breakthrough technologies, abbreviated as BTx, in a guidance that will be leveraged in a pilot program next year in advance of legislative reforms. The December 15 guidance document defines breakthrough medical devices and IVDs in the context of EU regulations, even though the concept is not yet included in the current MDR and IVDR. Qualifying BTx products must display a high degree of novelty and promise a “positive clinical impact” by addressing an unmet need. The guidance draws key themes from FDA’s Breakthrough Device Program, in particular the notion that assessors may consider allowing more uncertainty in the premarket phase balanced with a robust postmarket data collection plan for these products. The guidance directs notified bodies to prioritize files designated as BTx and to engage in “structured dialogue with manufacturers to clarify expectations regarding the generation of clinical evidence, the design of performance or usability studies, and the development of post-market surveillance and PMCF strategies.” It also establishes a role for input from EU expert panels. The planned BTx pilot program will seek to leverage the guidance process similar to the European Commission’s ongoing pilot for orphan devices. 

Normalizing notified body steps. The EU will more tightly manage procedures for notified body MDR and IVDR conformity assessments under the other major EU policy handed down this week that the Commission will implement independent of the legislative reforms. For the first time, the assessment bodies would be held to standardized timelines under a draft implementing regulation published by the Commission December 12. Notified bodies, for instance, would have 30 days to conduct an application review and sign a contract, 120 days to complete a quality management system audit, and 90 days to conduct required product verification steps. Those timelines don’t include periods when manufacturers are responding to requests for more information from the bodies, but the proposals would restrict the number of such requests during each phase of the conformity assessment. The rules would also put more controls around the re-certification process and how notified bodies set and monitor costs. Comments on the proposed procedures are due January 23. TEAM-NB, which represents EU notified bodies, has already publicly weighed in with concerns about the proposal, arguing that some of the timelines are too aggressive and that it “does not sufficiently account for the need for flexibility in handling complex or high-risk devices, or for parallel processing of multiple submissions.” 

FDA Picks

Big RWE change, PCCP numbers, recall gaps, and more:

Real-world evidence game changer? FDA says it will be more open to accepting real-world data sources lacking participant-level data in premarket submissions on a case-by-case basis. The agency included the significant update in the final revisions of its guidance on using real-world evidence (RWE) for device regulatory decision-making published December 17. The agency highlighted the shift in a press release it posted days earlier, touting that it will make it easier for manufacturers to leverage information from large clinical databases that only provide aggregate-level output. "This common-sense reform will unlock access to vast databases like cancer and cystic fibrosis registries that contain critical insights about how treatments work in the real world,” FDA Commissioner Marty Makary, MD, stated. The new final guidance directs companies that are including such data in a submission to “describe how lack of participant-level data does or does not affect RWE.” In the 2023 draft version of the revised guidance, FDA stated “it does not discourage” use of data sources without access to participant-level, but cautioned that it adds uncertainty. In the final version, the agency adds more assurance that a “sponsor’s inability to obtain participant-level data does not preclude FDA’s evaluation.” The practical implications of the stated shift remain to be seen. FDA has authorized more than 250 device applications that include RWE, but the agency suggests RWE-based authorizations have plateaued in recent years due to regulatory barriers. More generally, the revised guidance provides more details compared to the 2017 original about factors that sponsors should assess to demonstrate whether real-world data are relevant and reliable for a particular regulatory decision.

PCCP numbers. FDA has authorized well over 100 Predetermined Change Control Plans via 510(k)s, PMAs, and De Novo reviews, according to an analysis by Market Pathways. The types of modifications that FDA has allowed as part of PCCPs include AI algorithm updates, expansion of device capability, updated device designs and components, and certain types of labeling expansions. PCCPs grant companies the freedom to make pre-specified modifications without a new submission. For more details, see “The PCCP Picture: Iterating AI, Device Compatibility, Design, and Beyond” in Market Pathways.

Recall gaps. Insufficient staff limit FDA’s ability to conduct oversight of voluntary recall actions carried out by device companies, the Government Accountability Office concluded in a December 12 report. The congressional watchdog agency evaluated the device recall program in response to a request from Sens. Richard Durbin (D-Ill.) and Richard Blumenthal (D-CT). The agency, for instance, couldn’t meet its three-month goal of terminating recalls (ensuring manufacturers made all efforts to remove or correct the device). GAO recommends FDA conduct workforce planning to better address the recall process and consider seeking additional authorities.

MDUFA brainstorming. FDA and industry groups held a “brainstorming” session last month on problems and potential solutions for three device programs: De Novos, Pre-Submissions, and Third-Party 510(k) Review. The discussion happened at the third negotiation sessions for MDUFA VI user fees, held November 20, according to meeting minutes posted this week. The public minutes didn’t disclose any solutions that the parties reached. In general, according to the minutes, industry expressed “willingness to start working on commitment letter language, while noting the importance of better understanding current resources before determining whether additional resources are needed for each proposal before final agreement.”

Industry urges FDA not to rewrite postmarket rules for AI. Device industry groups urged FDA to leverage existing FDA device quality and postmarket requirements to monitor artificial intelligence-enabled devices rather than write special rules. “Duplicative or prescriptive new requirements for performance monitoring of AI-enabled devices [risk] undermining both patient safety and innovation,” officials from AdvaMed wrote to FDA. The sentiment aligns with several groups that responded to the agency’s recent request for comments on “measuring and evaluating AI-enabled medical device performance in the real-world.” Industry groups stressed that FDA has flexibility in its current rules to mandate postmarket studies or other controls when needed, and it shouldn’t paint all AI with the same brush. “For example, locked AI models, which do not change autonomously over time, are likely to present a similar level of risk as other non-AI software devices and therefore would not be expected to warrant special post-market monitoring,” emphasized Mark Leahey, president and CEO of the Medical Device Manufacturers Association.

Study safety reporting. FDA issued a guide describing investigator responsibilities for reporting safety issues to sponsors and institutional review boards (IRBs) during clinical trials for drugs, biologics and devices. The guide, intended primarily to clarify and consolidate older guides, finalizes a draft version published in 2021. The final version is largely consistent with the draft with some wording revisions.

Redrafted sex-based study guide. The agency published a new draft guidance this week outlining policies for studying differences between males and females and improvement female enrollment in studies of devices, biologics, and drugs. It revises a version of the draft that was published January 6, before the Trump administration took office. The new draft removes prior references to current legal requirements for firms to submit a “diversity action plan” as part of clinical trials (FDA has yet to finalize a guidance on the plans despite a mandate from Congress). It also removes references to gender as a distinct concept from sex, and makes other technical adjustments.

Global Picks

UK and Singapore partner, and more:

UK-Singapore pact. Companies will be able to engage UK and Singapore regulators at the same time to seek early advice on clinical trial planning and development under an “innovation corridor” agreement announced by the two countries December 12. The goal of the novel arrangement is to speed access to new innovations in both countries in parallel. The program is open to drugs and devices, and the first companies to leverage it will be those going through the Massachusetts-based incubator Flagship Pioneering, which is the first official partner of the program.

South Korea on robot surgery. The country’s Ministry of Food and Drug Safety issued a guidance (link in Korean) December 12 on premarket review considerations for advanced robotic surgery devices. It details expectations for clinical trial and other performance testing.

China glaucoma guide. The National Medical Products Administration published a draft guidance (link in Simplified Chinese) on China’s premarket review expectations for glaucoma drainage devices for minimally invasive surgery.

Resmed CEO will chair AdvaMed. Michael “Mick” Farrell has been elected to serve as chair of AdvaMed’s board of directors for the next two years. The Resmed chairman and CEO will begin the stint in January. Farrell has been active on the trade group’s board for the past 10 years, championing issues around digital health, international affairs, and other topics. He has led Resmed since 2013 and worked for the company since 2000. 

Reimbursement Picks

TAVR coverage reconsidered, CPT scrutiny:

Expanding TAVR coverage. CMS accepted Edwards Lifesciences’s request to extend Medicare coverage for transcatheter aortic valve replacement (TAVR) to asymptomatic aortic stenosis patients, reduce controls on where the procedure can be performed, and remove the coverage with evidence development policy that has been linked to national TAVR coverage for 13 years. In a request letter sent in July, Edwards pointed to study data it presented last year showing an advantage for TAVR over clinical surveillance in asymptomatic patients. It also argued that the current coverage policy is unnecessarily complicated based on the deep experience and strong standards that now exist for TAVR. “Outdated TAVR coverage requirements exacerbate barriers to patient access, leading to delayed patient care and poor outcomes,” the company stated. A proposed coverage determination from CMS is due in June.

Senator’s CPT scrutiny. Sen. Bill Cassidy (R-LA) continued his investigation of the American Medical Association’s handling of the CPT coding system last week, issuing a request for clinical stakeholders “with relevant experience and knowledge of CPT coding contracts with AMA” to respond to a questionnaire. The senator raised public scrutiny on AMA in October, accusing the group of charging exorbitant fees for the codes. “There may be nothing wrong here, but we should get answers to make sure the CPT system is working for the American patient and the American health care system,” he said December 9. 

Dates to Remember

For your calendar:

January 6. Comments are due to the European Commission on draft implementing regulations for setting up “regulatory sandboxes” under the AI Act.

January 17. Comments are due to Health Canada on proposed amendments to the Medical Devices Regulations to streamline device establishment licensing requirements.

February 2. FDA’s Quality Management System Regulation (replacing the Quality System Regulation) will take full effect.