FDA Intensifies Medical Device Oversight with Sweeping Regulatory Reforms

Due to the U.S. government shutdown, much of the attention surrounding the FDA focused on whether the agency would cease operations due to lack of funding. Nevertheless, the FDA remained steadfast in advancing reforms to medical device regulation during the shutdown, issuing a series of closely spaced announcements from late 2018 to early 2019 to deeply reform the medical device approval process.

In fact, the FDA focused intensively on medical device safety throughout 2018. It began by announcing the “Medical Device Safety Action Plan” in early 2018; reformed the 510(k) program in November; updated the De Novo review process on December 4; launched the new Safety Technical Evaluation Program (STeP) on December 14; and issued a call for comments on the final guidance for the 510(k) pathway on January 23 of this year.

Even during the government shutdown, efforts were not abandoned, as all these policies share a single focus: the safety of medical devices. More detailed implementation guidelines for these policies are set to be released in 2019, making it a watershed year for FDA medical device regulation.The FDA, which has always given the green light to medical device innovation, will maintain a full-scale security alert throughout the process.

In fact, adverse reactions to medical devices are unavoidable; however, if product safety issues and data security issues occur frequently, these become matters that regulatory authorities need to reflect upon.

Data from reports by the International Consortium of Investigative Journalists (ICIJ) show that, after investigating more than 8 million records related to implanted medical devices, they concluded that over 5.4 million adverse event reports had been submitted to the FDA in the past decade.Nearly 83,000 patient deaths were directly attributable, resulting in over 1.7 million injuries.

This reflects the absence of the FDA, the night watchman. But this time, the FDA is furious and has embarked on comprehensive reform.VCBeat previously reported on the FDA’s reforms to the 510(k) process,Next, we will provide a detailed explanation of how the FDA will update De Novo and newly launched safety plans.

The De Novo pathway deserves attention, as it serves as a key route to market for many innovative medical devices. For example, in the field of AI, the first FDA-approvedIDx'sAIDiabetic retinopathy screening was approved via the De Novo pathway.

The recent improvements to the De Novo pathway primarily focus on clarifying regulatory requirements, as evidenced by the FDA’s release of the document titled “Draft Guidance on De Novo Classification Regulations.” Once formally effective, this guidance will facilitate the appropriate classification of novel medical devices. For instance, the proposed regulations specify standards related to the structure, criteria, and transparency of the De Novo classification process, as well as the documentary and content requirements for submitting and withdrawing De Novo requests.

The draft for comments spans more than 70 pages,The most notable provision allows the FDA to conduct premarket production inspections of relevant medical devices as part of the De Novo review process.

In other words, the FDA will apply certain standards and procedures from the rigorous Premarket Approval (PMA) review to the De Novo classification of innovative medical devices.

This requires a thorough understanding of the FDA’s complex regulatory framework for medical device approval. Premarket Approval (PMA) is similar to the new drug review process, requiring rigorous clinical trials; it applies to products with the highest regulatory risk, typically Class III medical devices. In contrast, the 510(k) pathway only requires demonstrating that the device under review is substantially equivalent to legally marketed predicate devices. The De Novo classification, revised in 2014, is applicable to more innovative medical devices without existing predicates and posing moderate risks, thereby exempting them from the PMA approval process.

Approximately 70% of approvals are granted through the 510(k) pathway, while Premarket Approval (PMA) accounts for around 20%. Over the years, a total of 235 novel medical devices have received marketing authorization via the De Novo classification process.

The De Novo pathway has facilitated the market launch of multiple innovative digital health products, including the FDA’s first AI-approved product, the first adaptive hearing aid, and the first app prescribed for therapeutic use.

This means that many digital health companies must reevaluate their quality systems to prepare for FDA review. While the 510(k) pathway primarily pertains to traditional medical device manufacturers, changes to the De Novo classification process will impact a broader range of digital health companies.

“We aim to make the De Novo process more efficient and transparent by clearly delineating the entire review and application procedures. We also anticipate that a greater number of innovative medical device products will obtain clearance through the De Novo pathway, particularly as we take steps to improve the 510(k) regulatory framework. Continuous improvement of the De Novo process can help us better regulate emerging technologies, encouraging innovation in medical devices while ensuring patient safety,” stated Dr. Scott Gottlieb, Commissioner of the FDA, in a press release.

As the ancient Chinese adage goes, “In controlling floods, guidance is superior to containment”—a principle the FDA has similarly embraced. After tightening various regulatory pathways, the agency has sought to encourage the development of products specifically designed to address medical device safety issues. To this end, the FDA launched the Safer Technologies Program (STeP) on December 14, 2018.

Simply put,The signal sent by the STeP program is that if a product is safer than existing medical devices, even if it is less innovative, the FDA will still look favorably upon it. By joining the STeP program, manufacturers can engage in in-depth discussions with FDA review experts during the early stages of product development, thereby accelerating their path to market approval.

In 2019, the FDA will release additional operational guidelines to further clarify which characteristics qualify for the STeP program. The FDA also provided two examples. For instance, an orthopedic device may not be intended to treat a life-threatening or irreversible condition, but if it incorporates an innovative safety mechanism that reduces postoperative complications, it would be eligible for STeP. Alternatively, a medical imaging device that does not meet the criteria for breakthrough innovation may still qualify if it significantly reduces radiation exposure compared to similar devices, offering substantial benefits to both patients and physicians. Such devices, demonstrating safety advantages over existing counterparts, would be eligible for inclusion in STeP.

To better understand this brand-new STeP program, it is essential to first comprehend the FDA’s current Breakthrough Devices Program. Launched in late 2016, the Breakthrough Devices Program has since enrolled 110 products, eight of which have successfully reached the market.

“The Breakthrough Innovative Device Program” is designed to encourage the development of medical devices that enable timely and rapid diagnosis for patients, products capable of treating life-threatening conditions, and devices that can provide therapeutic benefits for certain irreversible diseases.These devices are required to provide novel methods for the treatment or diagnosis of diseases, offering significant advantages over existing therapeutic or diagnostic approaches., a prime example being the first blood test to aid in concussion diagnosis; it is deemed a breakthrough device because it can reduce the need for CT scans.

Not long ago, a new anti-cancer drug from mainland China received Breakthrough Therapy Designation from the U.S. FDA. The Breakthrough Therapy pathway is governed by regulations similar to those for Breakthrough Devices, but applies specifically to pharmaceuticals.

However, the FDA now considers innovation to be important, but safety is indispensable, and the two are complementary. This is reflected in the shift from the Breakthrough Devices Program to the STeP program. This is also one of the reasons why we say that the FDA’s regulatory focus on medical devices in 2019 will be safety.

Another reason is reflected in the FDA’s “Five-Year Plan.” From specific points to broader coverage, the FDA has been emphasizing safety regulation. The primary manifestation of this effort is the “Sentinel System” announced by the FDA in January this year.

The FDA’s “Sentinel System” and FDA-Catalyst, a strategic initiative the agency has been developing for nearly a decade, are now coming to the forefront amid advances in informatization and big data.

“The Sentinel System” is a tool used by the FDA for large-scale electronic safety surveillance: it enables the acquisition and analysis of real-world experience data from millions of patients using medical products, while safeguarding the privacy of individual medical records.

If, more than a decade ago, establishing an electronic surveillance system of such scale was merely the vision of a far-sighted leader, today it has become a national electronic system for monitoring the safety of FDA-approved drugs and all other medical products, known as the “Sentinel System.”

“The development of the ‘Sentinel System’ can be described as a watershed moment for FDA regulation. We are still exploring more ways to build this robust system and developing better tools to leverage data for enhancing safety,” said Scott Gottlieb.

“The “Sentinel System” is not only a critical tool for FDA safety monitoring, but also a key engine for methodological innovation at the FDA, and an important platform for advancing real-world evidence (RWE) research.

Prior to the implementation of the “Sentinel System,” FDA safety monitoring data for medical products primarily derived from adverse event reports submitted by patients, healthcare professionals, the pharmaceutical industry, and other sectors. These reports constitute part of the “passive surveillance” system within the FDA’s Adverse Event Reporting System (FAERS) and remain highly significant for safety researchers.

However, the “active surveillance” capability of the “Sentinel System” serves as a critically important complement to FAERS data. Rather than waiting for safety data to be submitted, it enables the FDA to directly access data as needed.

In fact, the FDA’s adverse event reporting system has long been regarded as a mere formality. Although the FDA maintains a system for reporting adverse events and complications, the volume of reports is severely inadequate. Within this voluntary reporting framework, physicians have no obligation to report observed adverse events, while manufacturers, despite being legally obligated to do so, are often the most reluctant to submit such reports.

This has led to the discovery of serious side effects in certain medical device products only months or even years after implantation, by which time tens of thousands of patients had already received them. A recent example includes certain paclitaxel-coated stents from Medtronic and Boston Scientific that are currently under investigation.

A study published in the Journal of the American Heart Association in December 2018 found an unexpected increase in mortality risk two years after the use of paclitaxel-coated devices in the knee. The FDA initiated an emergency investigation only after this risk was brought to light.

The “Sentinel System” was piloted starting in 2009 and fully implemented beginning in 2016. Currently, the Sentinel System relies primarily on insurance claims data as its source of information. Moving forward, the FDA aims to integrate more electronic health record (EHR) data into the Sentinel System for both pre-market and post-market surveillance. The FDA is also developing a knowledge management system and leveraging artificial intelligence to advance natural language processing capabilities, thereby facilitating the assessment of information contained within claims data and EHRs.

In medical innovation, innovation has always been regarded as a key driver of the industry. However, judging from a series of measures taken by the U.S. Food and Drug Administration (FDA), the FDA placed greater emphasis on the safety assurance of medical devices in 2019. Stricter regulatory oversight is gradually being implemented, extending beyond medical devices to encompass all medical products.

This data-driven regulatory approach has also significantly reduced human errors and omissions, thereby eliminating the breeding ground for corruption. A review by the International Consortium of Investigative Journalists (ICIJ) of data from the U.S. Department of Justice and the U.S. Securities and Exchange Commission (SEC) revealed that since 2008, medical device manufacturers in the United States and other countries have paid at least $1.6 billion to settle with regulators over corruption, fraud, and other violations.

This year, we will undoubtedly witness further actions by the FDA to strengthen regulatory oversight of medical device safety. The most noteworthy aspect of the FDA’s approach lies in how it balances innovation with safety in medical devices, continuously adapting its regulatory framework to accommodate the influx of innovative concepts and products.

In China, the Center for Medical Device Evaluation (CMDE) has long been regarded as the most stringent regulatory review body worldwide. Regarding post-market surveillance, the National Health Commission and the State Administration for Market Regulation jointly issued the Administrative Measures for Monitoring and Re-evaluation of Adverse Events Related to Medical Devices on August 13, 2018, which came into effect on January 1, 2019. These measures clearly define two key entities responsible for monitoring adverse events related to medical devices: one is the marketing authorization holder of the medical device, and the other is the National Adverse Event Monitoring Information System for Medical Devices established by the National Medical Products Administration.

Post-market surveillance methods are largely consistent with those of the FDA, wherein manufacturers proactively assume responsibility for monitoring and voluntarily report to the surveillance system.

Like the FDA, the NMPA is also exploring how to balance innovation and safety.

As early as 2014, the former China Food and Drug Administration (CFDA) issued the Special Examination and Approval Procedures for Innovative Medical Devices (Trial). In 2015, the State Council’s Opinions on Reforming the Review and Approval System for Drugs and Medical Devices (Guo Fa [2015] No. 44) and the General Office of the CPC Central Committee and the General Office of the State Council’s Opinions on Deepening the Reform of the Review and Approval System to Encourage Innovation in Drugs and Medical Devices (Ting Zi [2017] No. 42) were successively released. In January 2018, the National Medical Products Administration (NMPA) officially launched the Special Examination and Approval Procedures for Innovative Medical Devices.

As of December 31, 2018, a total of 197 products had entered the Special Review Channel for Innovative Medical Devices. Fifty-four products, including neurosurgical navigation and positioning systems, positron emission tomography (PET) and magnetic resonance imaging (MRI) systems, were approved for registration. A batch of highly innovative, technologically advanced products addressing urgent clinical needs was launched to the market, filling gaps in relevant fields and better meeting the public’s health needs.

It is commendable that the National Medical Products Administration (NMPA), while paving the way for innovative medical devices, has also prioritized the safety monitoring of such devices. Chapter IV of the Measures for the Monitoring and Re-evaluation of Adverse Events of Medical Devices, released on August 13, 2018, states:

Article 47 Holders of innovative medical devices shall strengthen proactive monitoring of such devices, formulate product monitoring plans, proactively collect reports of adverse events and product complaints, and conduct investigations, analyses, and evaluations.The holder of an innovative medical device shall submit a summary report on the monitoring, analysis, and evaluation of adverse events to the national monitoring agency every six months during the first registration cycle.. Where national monitoring agencies identify information indicating that a medical device may have serious defects, they shall promptly report such information to the National Medical Products Administration.

In terms of specific implementation details, domestic and international approaches differ, each with its own strengths. However, the FDA’s innovation in regulatory methodologies through the use of big data, AI, and other technologies is worthy of our reflection and reference.