FDA’s Newly Proposed Regulatory Framework for Artificial Intelligence and Machine Learning: What You Need to Know

By Catherine Mayone, Managing Partner, Publicis Health Consulting Services

7 min readApr 15, 2019


One of Scott Gottlieb’s last actions as the outgoing FDA Commissioner was to release a white paper, “Proposed Regulatory Framework for Modifications to Artificial Intelligence/Machine Learning (AI/ML)-Based Software as a Medical Device (SaMD),” which was intended as a discussion paper and request for public comment. At Publicis Health, a lot of people have asked us what this new regulatory framework means and whether or not any action is required. In this point of view, we provide a “CliffsNotes” version of recent FDA guidance, including the 20-page whitepaper, and considerations for any digital health and AI/ML investments.

The “CliffsNotes”

FDA issued its Mobile Medical Applications Guidance on September 25, 2013, then released an updated version on February 9, 2015. This document provided guidance if a mobile app needs to be considered a medical device and therefore subject to regulation. Mobile apps that are considered to be a medical device include those that:

  • Are an extension of an actual medical device, such as those that control the delivery of insulin on an insulin pump;
  • Use a mobile platform for medical device functions, such as an attachment of a blood glucose strip reader to a mobile platform to function as a glucose meter;
  • Perform patient-specific analysis, diagnosis, or treatment recommendations, such as those that use patient-specific parameters to calculate dosage.

Otherwise, apps that help patients self-manage their condition or track or document their medical condition are not considered medical devices, and FDA intends to exercise enforcement discretion (meaning FDA does not intend to enforce requirements under the Food, Drug, and Cosmetic Act). The first litmus test if the new regulatory framework needs to be applied, therefore, is whether or not the digital health solution that is considered a medical device falls under this guidance.

The impetus for the release of the latest framework originated with the 21st Century Cures Act signed into law on December 13, 2016, which amended the definition of “device” in the Food, Drug and Cosmetic Act to exclude certain software functions, including some that were in the 2015 guidance. The Act also called for FDA to develop its Breakthrough Devices Program, for which it released final guidance on December 18, 2018.

FDA’s latest proposed framework takes the 2015 guidance and accounts for the 21st Century Cures Act, and focuses on Software as a Medical Device (SaMD). The white paper uses the International Medical Device Regulators Forum’s (IMDRF) definition that this is “software intended to be used for one or more medical purposes that perform these purposes without being part of a hardware medical device.” In other words, FDA has long regulated medical devices and pharmaceutical products that are used for medical purpose, which it considers based on the 21st Century Cures Act to be “those purposes that are intended to treat, diagnose, cure, mitigate, or prevent disease or other conditions.” FDA now recognizes that the new world of digital health and therapeutics is evolving and it’s not just hardware or pills that serve medical purposes, but it can also include software.

However, FDA is not talking about all software. Consistent with the Mobile Medical Applications Guidance, software that is used for maintaining a healthy lifestyle, administrative support, electronic patient records, or for data transfer, storage or conversion are not subject to FDA regulation. In addition, medical devices historically have had software complementing the device, but what’s new is that the software may now be “intelligent” and uses techniques such as Machine Learning (ML), which the white paper defines as having “the capacity to learn based on training on a specific task by tracking performance measure(s).”

Examples of Mobile Medical Applications and AI/ML

Publicis Health reviewed FDA’s list of cleared mobile medical applications as of July 25, 2018. Here are two examples of mobile medical applications that required regulatory approval:

· Sanofi–My Dose Coach™ application received approval as a Class 2 medical device in March 2017 and is available in app stores. It provides patient-specific dose recommendations.

· Roche Diagnostics–ACCU-CHEK Connect Diabetes Management application received approval as a Class 2 medical device in March 2015. It also provides patient-specific dosage recommendations and connects to a blood glucose meter and online diabetes management system.

Presumably, while today’s versions of the software behind these medical devices may be fixed code that generate results based on proven dosing algorithms, it’s not hard to imagine how these types of medical applications will evolve to include intelligent, machine-learning software. There already are clinical tests being performed that demonstrate how AI can improve upon current mathematical models and deliver patient-specific glucose control dosing algorithms, so the possibilities for these mobile medical apps to evolve with AI/ML is just on the horizon. (Source: Journal of Diabetes Science and Technology, November 1, 2016, DeJournett L, DeJournett J)

The first FDA approved applications of AI/ML in healthcare have centered around imaging. Companies like IDx in detecting diabetic retinopathy, Viz.AI in using ML to automatically identify suspected LVOs (large vessel occlusions) on CTA imaging of stroke patients, and Imagen in detecting wrist fractures all received FDA approval between February 2018 and April 2018, and therefore most likely helped inform the framework around broader uses of AI/ML in SaMD.

The Next Generation is Digital Therapeutics

There are many start-ups in digital health innovating new mobile apps every day and, indeed, the majority of companies on the long list of FDA cleared mobile medical applications are ones that few people have even heard of. There are a few standout companies that are going beyond simply developing a mobile medical app and creating an entirely new category that stands to disrupt the industry.

  • Click Therapeutics, Inc. was the first company to trademark the phrase “Digital Therapeutics” on October 27, 2012. The company describes its mission as:
    Click Therapeutics, Inc. develops and commercializes software as prescription medical treatments for people with unmet medical needs. Through cognitive and neurobehavioral mechanisms, Click’s Digital Therapeutics™ enable change within individuals, and are designed to be used independently or in conjunction with biomedical treatments.
  • Pear Therapeutics, Inc., founded in 2013, puts a finer point on digital therapeutics, describing themselves as pioneers in Prescription Digital Therapeutics (PDTs), operating at the intersection of biology and software technology. The company defines PDTs as software-based disease treatments that are designed to directly treat disease, tested for safety and efficacy in randomized clinical trials, evaluated by FDA, and prescribed by healthcare providers. PDTs are designed and tested much like traditional prescription drugs with one distinction: rather than swallowing a pill or taking an injection, patients are treated with software. From the company’s website:
    Pear Therapeutics discovers, develops, and delivers clinically-validated software-based therapeutics to provide better outcomes for patients, smarter engagement and tracking tools for clinicians, and cost-effective solutions for payers. Every day, we push the boundaries of technology to transform medicine.

Both companies showcase their product pipelines on their websites just like any pharmaceutical manufacturer does, showing the product/TAs/indication and stage of development and regulatory approval. And, like other start up biotech and biopharma firms that are becoming big pharma’s innovation arm, both companies are now forming commercial partnerships with big pharma.

On April 18, 2018, Pear Therapeutics, Inc. announced a deal with Sandoz, a division of Novartis, to commercialize its two lead products, reSET® and reSET-O™. In addition to an upfront payment, the deal includes research and development funding, commercial milestones, and a profit split on net sales of both therapeutics. reSET® was cleared by FDA in September 2017 for the treatment of patients with substance use disorder, making it the first prescription digital therapeutic cleared with claims to improve clinical outcomes in a disease. This announcement was followed up with a January 9, 2019 press release announcing the U.S. commercial launch of reSET-O™ for patients with opioid use disorder (OUD) after its December 2018 FDA approval, the first time a PDT received Breakthrough Designation. This commercial partnership marks the first time that pharma reps will be detailing a digital therapeutic to HCPs.

That same week in January 2019, Otsuka and Click Therapeutics announced their agreement to collaborate to develop and commercialize digital therapeutics for patients with major depressive disorder (MDD). According to the press release, Otsuka agreed to commit capital to fully fund development of Click’s novel mobile application, “CT-152” for MDD, and to commercialize this application worldwide upon achievement of regulatory approvals.

Our POV: FDA and technology are ahead of industry

When Publicis Health clients come to us wanting to deploy mobile apps, we often hear, “Let’s design the app so it doesn’t need medical device approval.” The lack of pharma manufacturers on FDA’s list of cleared mobile medical applications is indicative of pharma’s reluctance to build digital health applications beyond patient-support-type of applications.

While this is understandable and often necessary given budgets and desired timeline, we believe we are at the stage in healthcare where the pace of technology has exceeded the industry’s pace of innovation and application of it. When this happens, industries and business models are disrupted as new entrants that aren’t afraid or disinclined to innovate against all barriers move in. We believe that intelligent patient services that can tailor solutions to individuals are the wave of the future. In some cases, these services will complement pills and medical devices, and in others, they will cannibalize medicine and healthcare delivery as we know it.

Given the lack of historical investment in mobile medical applications by traditional healthcare players — pharmaceutical manufacturers, payers, and providers — chances are likely that providing the requested feedback to FDA’s newly proposed AI/ML-SaMD framework is not at the top list of priorities for many companies. However, with the notion that both FDA and the technology are now ahead of the innovation of these traditional players, combined with the fact that an entire new category of digital therapeutics has emerged with FDA-approved products, the release of FDA’s whitepaper should be a wake-up call that software as medicine is very real and poised to disrupt the world as we know it.

Catherine Mayone is Managing Partner, Consulting Services at Publicis Health. She is a digital innovator and a creative and management consulting hybrid who brings together the talent and creativity of multiple disciplines to create new ideas and solutions.

Publicis Health’s consulting services bring together the real world of engaging and motivating patients and healthcare providers towards improved health and business outcomes, together with technologies and partners that can scale solutions quickly.

To learn more or for our latest thought leadership, connect with Cathy on LinkedIn



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