Guest Column | September 8, 2021

FDA's Evolving Regulatory Stance For SaMDs, Wearables, Digital Health & DTx

By Argie Zoubroulis, MS, and Mike Fahmy, MS; Otsuka Pharmaceuticals Development and Commercialization, Inc.


The FDA’s Center for Devices and Radiological Health (CDRH) issued a new policy on April 14, 2020, in an effort to maintain a patient-centric approach to the COVID-19 public health crisis titled Enforcement Policy for Digital Health Devices For Treating Psychiatric Disorders During the COVID-19 Public Health Emergency, recognizing the population’s need for such therapies. This enforcement policy allowed for the distribution and use of computerized behavioral therapy (CBT) devices for psychiatric disorders without need for premarket notification, i.e., 510(k) submission, and without compliance to certain regulatory requirements, such as Unique Device Identifier (UDI), Product Device Registration and Listing, Reports of Corrections and Removals, and Special Controls. Special considerations with respect to labeling were listed in the policy to guide Software as Medical Device (SaMD) use and so that SaMD users would be aware that these SaMDs are not 510(k) cleared. As of the date of this article, this policy continues to be in effect and has served as part of the foundation for the Department of Health and Human Services’ (HHS) proposal to permanently roll back regulatory requirements for a myriad of medical devices.

On Jan. 15, 2021, during the transition between the Trump and Biden administrations, under executive order by the Trump administration, HHS posted to the Federal Register (FR) a notice that proposed to make permanent the 510(k) rule relaxations in response to the COVID-19 public health crisis. This FR notice proposed to make exempt 83 Class II medical devices and one unclassified device of various FDA product codes, which are used to classify medical devices. Of particular interest to SaMD developers, this notice also included FDA product code PWE: Computerized Behavioral Therapy Device for Psychiatric Disorders. Under this notice, medical device manufacturers developing new medical devices characterized by the FDA product codes specified in the notice would not have to pursue 510(k) clearance ahead of marketing.

Permanent issuance of the rule relaxations in this FR notice would enable these 83 Class II medical devices and one unclassified device to be registered with FDA and marketed without need for FDA review through a pre-market notification, i.e., making these FDA product codes 510(k)-exempt. This notice was supported by adverse event data compiled by HHS from a publicly accessible and voluntary adverse events database (MAUDE database) showing low risk.

Following this notice, industry had the opportunity to post comments to the public docket for agency review ahead of any permanent rule issuance on: (1) whether premarket review should be permanently waived for some or all of these product codes and (2) views on ways to improve the 510(k) premarket notification program. Regarding FDA product code: PWE, a series of industry leaders in prescription digital therapeutics (PDTs) and digital therapeutics (DTx) (Pear Therapeutics, Limbix Health, Cognoa, AppliedVR) consistently commented that while industry appreciates the efforts made by HHS to support the least burdensome approach, proceeding with a blanket exemption may empower unscrupulous or unfamiliar developers to place unsafe and/or ineffective products in the market. A portion of AppliedVR’s public comment reads, “A second major problem with the proposed rule is that categorizing SaMD and SiMD as Class I devices risks some nefarious manufacturers to pander misleading marketing claims that could endanger the public. Regulated devices, both 510(k) and PMA, have restrictions on advertising and labeling claims. Class I devices do not have those types of restrictions. SaMD and SiMD have enormous positive potential, however, if such devices are not adequately safety-checked, they could lead to significant morbidity and even mortality. SaMD and SiMD are not equivalent to Class I devices like a tongue depressor. Failing to have 510(k) or PMA would create the risk of snake-oil marketing akin to Theranos.”

Further, leaning on the MAUDE database to support making these 510(k) exemptions permanent may be somewhat useful but is imperfect, especially since FDA product codes specified for Emergency Use Authorization/enforcement discretion did not have adverse event reporting guidance until September 2020. In addition, HHS’ proposal considered only the safety lens and made no considerations regarding these medical devices’ effectiveness. With specific regard to SaMDs, some of which fall under FDA product code: PWE, these products, which are intended to diagnose or treat, have not yet been well studied to support permanent 510(k) exemption.

On April 16, 2021, this FR notice was withdrawn and Acting FDA Commissioner Janet Woodcock cited that HHS, the department responsible for overseeing the FDA, did not consult with the FDA ahead of issuing the FR notice and that the notice “was published without adequate scientific support, that the Notice contained errors and ambiguities, and that the Notice is otherwise flawed.” The statement proceeded to reject the rationale upon which the FR notice was issued, stating that relying on safety data logged in a voluntary adverse event database (MAUDE database) is not sufficient to determine the safety of a device and whether a 510(k) is necessary. The FR notice did not document how effectiveness would be assessed in the proposal.

In this case, the FDA and industry were aligned in that, left unregulated, SaMDs, apps, wearables, and other kinds of technology have not yet been robustly vetted from a safety and effectiveness perspective. Unregulated SaMDs, apps, wearables, etc. can cause confusion to patients, as a myriad of products with varying levels of rigor and scrutiny would inundate users and even cause harm due to a lack of efficacy and unchecked safety. An FDA-cleared SaMD has a clear intended use with a scientifically backed indication, much like an approved drug. Without a standard approach to this scientific rigor and proper oversight, a series of “placebo-type” products would be available side-by-side with products that have been tested and properly validated. To better regulate this kind of telemedicine technology, clinical evidence is imperative to start validating these kinds of technologies in the field.

The Launch Of The Digital Health Center Of Excellence & FDA Listening Sessions

Even prior to the FR notice (and its subsequent withdrawal), CDRH acknowledged this need and launched the Digital Health Center of Excellence (DHCoE) in the fall of 2020 to provide regulatory advice and support to the FDA’s regulatory review of digital health technology. Through industry and agency coordination, the DHCoE aims to map out modernized policies and increase digital health product expertise at CDRH to help guide industry stakeholders while maintaining a focus on the healthcare provider perspective and patient-centricity.

Listening sessions conducted by the DHCoE in October and November 2020 were intended to introduce the DHCoE and seek feedback from industry. These listening sessions have indicated a need by industry for the FDA to provide better clarity on:

  • when FDA approval is required;
  • transparency about regulatory pathways;
  • what is regulated and what is not; and
  • how stakeholders should pursue approval.

Further, as part of these listening sessions, the FDA stated that it would like to explore how patient data can be securely moved to electronic medical records and other data repositories to improve healthcare as well as ways to assure patients that their data are protected and that privacy and security standards are followed. In this way, digital health therapeutics can function more like performance apps to collect insights on the patient’s health status and communicate that information to the healthcare provider. The DHCoE would like to engage patients, who are the consumers of digital therapeutics, to have a larger role in monitoring their own healthcare and to better understand digital healthcare. The DHCoE is motivated to provide patient-centric and healthcare practitioner education to help chart this new medical device field. With this education, patients may be better able to distinguish clinically validated, high-quality treatments among the myriad of unregulated general consumer health applications. In terms of next steps, the DHCoE is looking to foster partnerships between the agency and industry to establish a working relationship moving forward; however, no substantive updates have been communicated since the listening sessions in the fall of 2020. According to the DHCoE website, industry is encouraged to forward questions to a DHCoE email address.

What You Can Do To Influence Future Regulations On SaMDs, Wearables, Digital Health & DTx

From an industry perspective, inter-company trade organizations such as Digital Therapeutics Alliance (DTA) and AdvaMed are looking to facilitate DTx guidance from FDA via public docket and direct correspondence with CDRH. You can join these company trade organizations and help align on the direction of SaMD and DTx through discussion. Another avenue you should consider is initiating discussion related to your SaMD or DTx directly with CDRH through your product’s FDA reviewers. Straightforward agency input regarding standardized guidance for the clinical evidence bar for SaMDs is essential. Guidance regarding randomized controlled trials (RCTs) to test SAMDs and DTx, with clear direction regarding time and attention to placebo match, adherence, and standard of care (SOC) considerations, is crucial to establish the regulatory bar. At this time, there is no clear insight as to when these draft guidelines will be published; however, industry can leverage the company trade organization platform to broach and facilitate this topic and lay a foundation for SaMD regulatory expectations. Upon issuance of draft guidelines, industry will have a designated window of time to make recommendations through public comment to the docket prior to final issuance.

Considering this recent regulatory positioning by HHS to soften the regulatory burden surrounding SaMDs, it would be prudent for industry and the FDA to align on the rigor required to successfully demonstrate safety and effectiveness of these products and move them to the market. The need for SaMDs and DTx has been greatly emphasized during the COVID-19 public health crisis; however, the regulatory infrastructure to support SaMDs has not been fully defined, causing some confusion and disruption. A delicate balance must be met between applying scientific rigor and encouraging innovation in this space. This is best served by ensuring the key stakeholders in this space (developers, patients/caregivers, payers, and regulators) are fully engaged and leveraging all avenues to connect. By approaching SaMDs with a renewed motivation to educate patients and healthcare practitioners and clearly identify the barriers to regulatory clearance or approval, both industry and the FDA can help to better guide patients as they navigate this burgeoning and rapidly developing new field of digital healthcare and bring new valuable tools to their arsenal.

About The Authors:

Argie Zoubroulis specializes in regulatory affairs work for both medical devices and pharmaceuticals at Otsuka Pharmaceuticals Development and Commercialization, Inc. She acquired her M.S. degree in biomedical engineering from Drexel University and her bachelor’s degree in biological sciences at the University of Pittsburgh. Prior to joining Otsuka, Argie worked for Wills Eye Hospital and Parker Hannifin in similar capacities. She has a special interest in digital health and its potential synergistic capacity with drugs.

Michael Fahmy is executive director in global regulatory affairs at Otsuka Pharmaceuticals Development and Commercialization, Inc. He has been with the company since February 2013 and is leading the regulatory strategy for the development of several therapeutic areas and led the first FDA-approved digital medicine. Prior to Otsuka, Michael was at Bristol Myers Squibb for more than nine years in regulatory roles, including as global labeling strategist covering the U.S., EU, Japan, and other key geographical areas. He has a master’s degree from Temple University in quality assurance/regulatory affairs and a bachelor’s degree in biological sciences from Rutgers University.