How DTx Companies Can Best Work With the FDA When Bringing Groundbreaking Digital Therapeutics to Market

The digital therapeutics (DTx) industry aims to introduce new and innovative approaches to healthcare delivery through technology. Because of its novelty, many companies in this space are unfamiliar with the steps necessary to bring a new digital intervention to market – a process that can take several years. Thus, being intentional with the way they interact with the FDA can save DTx companies time and make their journeys less arduous.

Regulatory pathways for DTx interventions

Pharmaceuticals follow a very distinct path to commercialization through several phases of clinical trials. Digital therapeutics and medical devices, however, can follow a multitude of regulatory pathways depending on their uniqueness, the risks they pose to patients, complexity, and other factors.

Interventions that are low- to moderate-risk and are substantially equivalent to an existing legally marketed device require a 510(k) premarket notification, whereas higher-risk interventions or those using more novel approaches require more extensive evidence of safety and efficacy through a De Novo request to classify the device and establish special controls. Obtaining clinical validation through the De Novo classifications therefore takes longer than through the 510(k) premarket notification.

The challenge

As a new family of treatments, digital therapeutics have different evidence requirements for gaining FDA approval than do medical devices. While digital therapeutics using a cognitive-behavioral approach have been able to use Pear Therapeutics’ previously cleared products (RESET, RESET-O, Somryst) as predicates in 510k submissions, most other digital therapeutics today do not have existing predicates on the market and necessitate a De Novo classification.

Regardless of which regulatory pathway a new technology must follow, the FDA’s requirements for clinical evaluation can differ greatly from one intervention to the next. It is important to remember that the FDA is operating under the constraints of the law. As a sponsor, you’re likely not fully versed in the legal and regulatory requirements, so engaging with the FDA regularly throughout clinical development for feedback is crucial to understanding what’s needed to progress your research.

Planning for FDA interactions

There are several different types of meetings DTx manufacturers can request with the FDA depending on the nature of the conversation. During early study planning, informational meetings present opportunities to receive initial feedback on general development plans and regulatory strategy.

To address specific topics within a development plan, such as study design, data collection, and regulatory pathways, more formal pre-submission (pre-sub) meetings are required. For example, a DTx company may have specific endpoints in mind it thinks are ideal for meeting study objectives, but the FDA may actually want to see something different. It is better to understand the agency’s expectations early on. Thus, one or two pre-submission meetings prior to conducting pivotal studies are strongly recommended: one to get input on endpoints and design at a high level, and again later once the study is fully fleshed out to discuss more fine-grained details, including the statistical approach, an area where the agency has been quite vocal.

Once DTx manufacturers have made it through study planning, they should meet with the FDA at pivotal times throughout the development of a digital therapeutic to discuss study results and future research plans. It can be valuable to initiate these conversations at the end of Phase 1 and 2 trials, before applying for a 510(k) or De Novo classification. Doing so ensures that FDA’s thinking has not changed during the time that the study was conducted, and de-risks the submission. For example, I have seen several instances where FDA agreed with a sponsor on the appropriate pathway for a product in a presubmission, then had new thinking later as a result of devices that had been since cleared, or guidances that had been since published.

It can be several months before such meetings occur, as writing a submission can take several weeks (2-3 months on average) and then more for the FDA to properly review a submission and set a date. During these conversations, the FDA may also provide feedback that necessitates DTx manufacturers making changes to their clinical development plans.

While it is rare for the agency to deny a meeting request, it is not so uncommon for the resulting meeting to yield frustrating results for sponsors (i.e. a series of “FDA cannot comment” responses), particularly if they have not provided enough information for FDA to comment substantively. It is incredibly important for applicants to account for these possibilities when planning study timelines and give themselves sufficient time to incorporate any suggested updates to minimize delays.

Common misconceptions about working with the FDA

Sponsors often assume they should only approach the FDA with their final thoughts or when they think their clinical development plan is complete and ready to launch. This is a misconception as the FDA can provide invaluable input when DTx manufacturers are still figuring things out.

Meeting with the FDA does not mean a DTx manufacturer is committed to doing whatever it proposes; rather, a meeting is a way for sponsors to learn how the FDA would react if they did everything according to their plan. The purpose of the presubmission meeting, therefore, is to identify holes in the sponsor’s strategy so that it can be improved and chances of success in 510(k) or DeNovo can be increased. With this in mind, it can actually be detrimental for sponsors to meet with the agency too late after having spent a lot of time and resources on a path that it turns out, based on FDA feedback, does not work well for the development of their digital therapeutic.

While the FDA ultimately has a say in bringing a DTx product to market, it is not the agency’s job to lead decisions regarding a manufacturer’s research. The FDA can inform you of the implications of choosing one path over another and help you determine whether your approach will lead to clearance.

But the agency nonetheless expects sponsors to propose solid plans for clinical development. Therefore, it is critical for DTx companies to be highly intentional in the way they phrase questions and request feedback in their submissions and during live meetings with the FDA. Sponsors never should outright ask the agency to tell them what to do; instead, they should explain their plan and then ask if the agency agrees with the proposed course of action.

Navigating the regulatory landscape for digital therapeutics can be a complex and lengthy process, but understanding the FDA’s requirements and engaging with them strategically can significantly streamline this journey. It is crucial for sponsors to view the FDA as a collaborative partner rather than just a hurdle. Regular and well-planned interactions with the FDA at appropriate stages can provide invaluable guidance, prevent costly missteps, and ensure that development plans align with regulatory expectations.

Ultimately, the goal is to bring innovative digital therapeutics to market efficiently and safely. By being intentional and strategic in FDA interactions, sponsors can turn regulatory challenges into opportunities for growth and success.