The US Food and Drug Administration (FDA) issued a request for comment on Monday that sets forth a proposal for a new framework on the regulation of software applications for use with one or more prescription drug products.
The agency’s newly adopted digital health approaches “are still in their early stages,” FDA Commissioner Scott Gottlieb said
Monday in remarks at the Reagan Udall Foundation annual public meeting. “A lot of these technologies haven’t advanced as quickly when it comes to the delivery of medicines because the regulatory pathway has—at times—seemed uncertain. Our aim is to provide that certitude.”
Gottlieb called for “taking the same forward learning approach” as FDA’s relatively new risk-based regulatory approach on software as a medical device (SaMD) or applying “some of the same approaches to apps that are coupled to drugs.” He argued “we’ll never fully realize the potential for digital tools to improve health until we adopt” an SaMD-based framework for integrating drug-associated apps and software into drug development.
The newly proposed framework coincides with an agency-wide paradigm shift
to support digital health. The work—fueled by recent legislative actions seeking to modernize the care delivery system through greater adoption of emerging technologies for targeted therapies—are largely aimed at making the rapidly growing body of real world data (RWD) more robust to ultimately increase the use of real world evidence (RWE) that can support decision-making on FDA-regulated medical products.
FDA’s role in developing, adopting and advancing digital health technologies, such as wearables and sensors, spans across the care continuum and total product lifecycle. “These efforts highlight a critical opportunity we have—to advance healthcare, and promote advances in how we develop new medical products and how patients access them,” Gottlieb argued. “And that opportunity is the growing convergence between digital and traditional healthcare,” he said.
Similar to the SaMD framework FDA’s Center for Devices and Radiological Health (CDRH)
developed about four years ago in collaboration with the International Medical Device Regulators Forum (IMDRF), the new approach for drug-associated apps will seek to provide flexibility and the necessary safety measures, while being adaptable to the iterative nature of the software. CDRH is using the IMDRF SaMD framework to create a new regulatory pathway for software, known as the Pre-Certification (Pre-Cert) program. The aim is to remove regulatory barriers and premarket challenges to fast-track products developed by the program participants.
The design of CDRH’s program has attracted the attention of many in the tech space, though it has also raised
questions among some, such as Congressional leaders partly over allowing participants to bypass certain premarket requirements.
A new docket
in the Federal Register
was established Monday for stakeholders to provide feedback on FDA’s newly proposed framework for regulating apps intended for use with prescription drugs. The approach, however, would only apply to drug sponsors who chose to disseminate software for use with one or more of their own prescription drugs, Gottlieb clarified.
“We’re committed to considering and weighing all comments as we develop draft guidance based on this approach,” including “the examples we’ve used to illustrate when software output is considered promotional labeling; when it may be referenced in required labeling as part of a New Drug Application or Biologics License Applications submission; and when it’s an essential component of a drug-led, drug-device combination product,” Gottlieb said.
Under the proposal, the output of certain software, which includes material presented to an end user, such as a patient, caregiver or health care professional, generally “would be regulated as drug labeling.”
Gottlieb’s remarks highlight several other similarities with the envisioned Pre-Cert, which is reportedly on track to be open
for business by the end of next year. These similarities include a shift toward subjecting lower-risk apps to post-market surveillance and monitoring, as opposed to reviews of premarket drug applications, and the notion that “one size doesn’t fit all.”
Apps for medication adherence, which are expected to proliferate due to an aging population, would be covered by the newly proposed framework. Other examples include apps for patient-specific dosing and symptom trackers. An app could also fall within the scope of the framework even if its functionality does not fall within the definition of a medical device, as would be the case with software that is considered prescription drug use-related software.
The agency expects that “the output of most apps used with prescription drugs wouldn’t need to come to the FDA for premarket review,” according to Gottlieb. “Since we propose to treat most apps as promotional labeling, it means that only that the final display or communication the software delivers to end users would be sent to the FDA at the time of dissemination,” he added.
Under the new framework, there are two situations in which information about prescription drug use related to software would be subject to premarket review. These involve a substantial amount of evidence of an impact on a clinically meaningful outcome and when an app serves a critical role in achieving at least one of the intended uses of a drug-led combination product.
All new regulatory approaches on digital health will ultimately be harmonized across the entire agency, according to Gottlieb.