How Digital Therapeutics are Transforming the FDA

Digital therapeutics are poised to dramatically change the pharma landscape by marrying software with clinical interventions to produce more effective and economical treatments and therapies.

As with any transformational change in a regulated industry, the development of digital therapeutics has initiated a regulatory transformation as well, one that promises to redefine the inner workings of the FDA. Let’s explore how Digital Therapeutics are transforming the FDA.


Limitations of the Current Regulatory Landscape

With the current FDA approval process, it can take 12 years, on average, and more than $350 million, to bring a new drug to market. About half of this time is spent on clinical trials.

The current drug approval process is linear and assumes a lengthy period of clinical trials – Source


For medical devices, FDA approval requires successful completion of one of five pathways to market. The simplest of these is for Class I devices, which are exempt from pre-market submission to the FDA for approval. The most rigorous is a Pre-market Application (PMA) for Class III devices, which require both a scientific and regulatory review that evaluates a device for safety and effectiveness. The PMA process must be completed for each new device. Data or results for a comparable product, no matter how similar, are not sufficient.


The FDA’s multi-step approval process was developed to assure the public that the drugs and medical devices they are prescribed are safe and effective. It ensures that companies wishing to bring a new drug or device to market use a rigorous, scientific process that results in a drug or device that will remain essentially unchanged throughout its lifecycle.


Software development, the heart of digital health and therapeutics, is different.


Development of Digital Therapeutics Needs to be Agile

Unlike drug development, software development is not a linear, one-and-done process. It is an iterative process. Tech enhancements follow feedback from users, and bug detection drives ongoing updates and code revisions. Most software is continually under development, so agility is key to being responsive to the market.

The Spiral software development model is one way to represent the iterative nature of software development – Source


Software updates continue throughout the lifecycle of any digital product. Just think of the operating system on your laptop or the apps on your smartphone. Neither remains unchanged over time.

Given the dynamic nature of software development, the FDA’s 12-year approval process is simply untenable. By the time one version of the software receives regulatory approval, it will be hopelessly out of date. And if regulators try to review each new iteration of a software package as it’s developed, they will be stuck in an endless loop of development, review, and approval.

Yet leaders in the digital therapeutics industry say they value the legitimacy that regulatory approval brings and are actively working towards a modified review process that will better support their industry.

Additionally, the current approval process isn’t set up to handle digital therapeutics that are solely a delivery mechanism for already-proven therapies. One example is 2Morrow Health’s behavioral therapy app, which delivers the already-proven Acceptance and Commitment Therapy (ACT), an approach to mindfulness training that improves well-being.


Should software that delivers a recognized therapy go through the same intensive clinical testing as an untested or unproven treatment?

Some leaders in digital therapeutics say no.

Jo Masterson, Co-Founder and Chief Operating Officer at 2Morrow, has said:

“We’re not trying to prove that ACT can be effective for chronic pain — there’s 19 randomized controlled trials published already saying it can, it has strong empirical evidence. But we’re just trying to prove that we can also deliver this approach via the technology. To expect people to do five-year randomized, controlled trials is not very relevant because the technology will be old by the time the data comes out. If what you’re testing is the technology itself, we have to figure out reasonable ways to quickly assess things.”

Leaders in digital therapeutics also argue that not every digital health and wellness product may need to satisfy the rigor of regulatory review and approval. Glooko CEO Rick Altinger has suggested using a regulatory approach that draws a distinction between digital health, which would be subject to regulatory approval, and digital wellness, which would be consumer-grade products and not subject to regulatory approval.

Another line of distinction is being drawn between digital health companies that seek payer reimbursement and those that do not. Pear Therapeutics’ Chief Commercial Officer Alex Waldron acknowledges the importance of regulatory approval for securing reimbursements from payers, saying, “I think, historically, payers have had a hard time paying for something unless it has been objectively viewed as well.”

In an effort to define the boundaries of this new digital health industry and influence the transformation of the regulatory landscape, digital therapeutic leaders formed the Digital Therapeutics Alliance. The Alliance defines the industry as producing “clinically-validated disease management and direct treatment technologies,” codifying the desire of its members for some form of formal product testing and approval process.


FDA Responds to the Evolving Nature of Digital Health

It was industry itself that made the FDA aware of the need for a revamped process that addresses digital therapeutics and the new technologies they incorporate.

In 2015, Pear Therapeutics requested that the FDA review and approve its software-only substance abuse therapy, reSET. As Alex Waldron tells the story, the FDA’s response was to say that no other company had ever come to them saying that they wanted to be regulated.

The rise of digital health demands a new paradigm of understanding and regulation – Source

Within two years, Congress passed the 21st Century Cures Act and the FDA published its  Digital Health Innovation Action Plan. The plan declared:

“FDA can help encourage digital health innovation by redesigning our policies and processes and modernizing our tools so that they match the needs of digital health technology, and providing clarity on those policies and processes so that manufacturers and developers know what they need to do.”

Launch of Pre-Cert Program

In July 2017, the FDA announced the Digital Health Software Precertification (Pre-Cert) Program. That September, it launched a pilot of the Pre-Cert Program.

The pilot brings together a cross-section of digital health companies, healthcare stakeholders, and the public (including patients and caregivers) to collaborate on the development of the parameters and processes to be used in the Pre-Cert program.

Similar to Europe’s CE marking system, the Pre-Cert Program is intended to examine the company developing the technology, not the product itself. This approach will have the FDA confirm up front that the developer has a “culture of quality and organizational excellence” before considering any of the developer’s products.

With its Software Pre-Cert working model, the FDA turns its review and approval process on its head by focusing on the developer first, not the product – Source


In announcing the Pre-Cert Program on the FDA blog, Dr. Scott Gottlieb, M.D. declared:

“The goal of our new approach is for FDA to, after reviewing systems for software design, validation, and maintenance, determine whether the company meets the necessary quality standards and pre-certify the company. Pre-certified companies could submit less information to us than is currently required before marketing a new digital health tool. In some cases, pre-certified companies could not submit a premarket submission at all. In those cases, the pre-certified company could launch a new product and immediately begin post-market data collection. Pre-certified digital health companies could take advantage of this approach for certain lower-risk devices by demonstrating that the underlying software and internal processes are sufficiently reliable. The post-market data could help FDA assure that the new product remains safe and effective, as well as supports new uses.”


Collaboration is key

The FDA is currently collaborating with a group of industry leaders and healthcare stakeholders to develop a new regulatory framework that starts with developer pre-certification.

As part of this collaboration, the FDA is visiting the nine participating digital health companies to learn about their development and testing processes. What they learn will be used to develop a rubric to determine, measure, and document a developer’s “culture of quality and organizational excellence.” Ultimately, the rubric will be used to pre-certify developers who meet the qualifications.

The FDA will host a series of quarterly meetings for the public and other stakeholders to offer their input to the development of the Pre-cert Program. Already, the FDA hosted a public workshop in January 2018 and a user session in May 2018. Additional public workshops and user sessions will be scheduled as work on the new regulatory framework progresses. The FDA invites all stakeholders, including patients and caregivers, to get involved with the Pre-Cert Pilot program.


A Transformed Regulatory Framework

At the May 2018 user session, the FDA shared a more complete picture of the proposed regulatory framework, which is made up of four components.

The FDA’s new regulatory framework for digital health takes shape – Source


Pre-certification of developers is the first step in a four-phase program. A level of pre-certification will be assigned, based on an assessment of quality processes and organizational excellence demonstrated by the developer.

A determination of whether a product review is needed follows. For developers who receive pre-certification, the type of product review required will be determined, based on a risk assessment of the product and the developer’s level of pre-certification.

A streamlined review process is next. This premarket review is aimed at assuring safety and effectiveness. It will take into account the developer’s pre-certification status and product history.

Monitoring real-world performance rounds out the key components of the framework. Three types of real-world performance data (RWPD) will be monitored: health data (RWHD), user experience data (UXD), and product performance data (PPD). Together and individually, these data types will be used at both the organizational and product levels. These data will help determine if a developer receives, maintains, or changes pre-certification level. Regarding the product, these data will be used to monitor the ongoing safety and effectiveness of the product and to determine the validity of product claims.


The Path Ahead

In a relatively short period of time, the FDA has taken on the challenge of transforming its regulatory process to meet the needs of the emerging digital health industry.

While upholding its core mission to ensure public safety, the FDA has partnered with industry and stakeholders to transform the regulatory landscape, promising to make it more agile and in sync with digital development cycles.

Moving quickly, the FDA is committed to launching Pre-Cert 1.0 by 2019 – Source


Looking ahead, the FDA plans to launch Pre-Cert 1.0 by the beginning of 2019. Once launched, it will test and refine the Pre-Cert Program for the following year. This is an ambitious timetable.

For the program to succeed, both industry and regulators will need to adopt new ways of operating. The regulators appear to be moving at an unprecedented pace. Will industry be able to keep up that same pace over the next couple of years? Only time will tell.

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