As previewed by Commissioner Gottlieb several months ago (see our earlier post here), FDA published a notice in the Federal Register on November 20, 2018, to propose a new framework for “prescription drug-use-related software.” The Agency defines this digital health category widely as software disseminated by a prescription drug sponsor for use with the sponsor’s prescription drug(s). Last spring, the Commissioner stated that FDA would be seeking input “on how to support the development of digital health tools that are included as part of approved drugs.”  The goal in establishing the framework, Gottlieb stated, would be “to develop an efficient pathway for the review and approval of digital health tools as part of drug review, so that these tools reach their full potential to help us treat illness and disease, and encourage synergies between software and therapeutics that meet FDA’s gold standard for safety and effectiveness.”

This policy development is significant, not only because it is one of CDER’s first policy statements on digital health associated with pharmaceuticals (see a few of our earlier posts about pharma-related digital health here), but also because it implicates a broad range of information that could be made available by prescription drug sponsors through software used with their products. We encourage prescription drug sponsors with any interest in providing digital health solutions, including through collaborations, to review the Federal Register notice and consider submitting comments to FDA.

Here are a few key takeaways from FDA’s notice:

• Under the proposed framework, software with the same drug-related functionalities will be subject to different regulatory approaches by FDA, depending on the developer of the software. FDA will apply the proposed framework to prescription drug-user-related software developed by or on behalf of pharmaceutical manufacturers, and a different approach to drug-related software developed “independently” by third-party software developers and other entities that are not prescription drug sponsors.

• It is unclear from the notice how the proposed framework, including the evidentiary standards described in the Federal Register notice, will align with other FDA initiatives such as the use of real-world evidence for drug development and the pre-certification program (see our earlier post here).

• An important question for prescription drug sponsors in particular is whether the proposed framework will encourage continued digital health innovation, including through collaborations, or whether FDA’s proposal will create challenges that may discourage advances in this area.

Overview of the Proposed Framework

In the proposed framework, FDA notes that digital health software functions should be assessed under FDA’s “device” authorities, in addition to “drug” and “biologic” authorities in some cases (for background, see this FDLI article). In the proposed framework for prescription drug-use-related software, FDA focuses almost exclusively on the “output” of prescription drug-use-related software, which is the material presented to an end user of the software—such as a patient, caregiver, or healthcare professional. The Agency explains that FDA will consider the output of prescription drug-use-related software to be drug labeling because it “accompanies” a specific drug. Information about this software output may either be included in FDA-required labeling or constitute promotional labeling. This determination turns on the manner in which the output is used with the prescription drug, and the notice sets forth several examples to illustrate the proposed framework.

If considered promotional labeling, a prescription drug-use-related software output would be subject to the same regulations as other promotional materials disseminated by or on behalf of the drug sponsor, requiring submission to FDA’s Office of Prescription Drug Promotion (OPDP) or Advertising and Promotional Labeling Branch (APLB), as appropriate. In the case of software outputs that make certain recommendations, FDA recommends that drug sponsors seek pre-dissemination review by FDA through the voluntary advisory comment process for promotional materials. FDA also generally notes that it is the responsibility of the drug sponsor to ensure the reliability of the software it disseminates.

FDA states that the proposed framework applies only to software disseminated by or on behalf of a drug sponsor, and does not apply to software disseminated by third-party developers who “independently” develop or disseminate software for use with prescription drugs. Given the breadth of digital health collaborations in the marketplace, FDA can expect comments seeking clarity on how the Agency defines “independently” under this proposed framework. FDA expects to issue draft guidance based on public comments to the proposed framework.

Commenting on the Proposed Framework

Companies who are marketing or developing digital health products will want to carefully review the proposed framework and consider the implications for their product portfolios. Companies should consider submitting comments to FDA, which could include supporting particular aspects of the proposed framework, noting concerns about ambiguity or implementation, or suggesting changes in the Agency’s approach. The Agency has established a docket for public comments, which will remain open until January 22, 2019.