The U.S. Food and Drug Administration (FDA) issued a notice in the Federal Register last week requesting public comment on a proposed framework for software applications disseminated by or on behalf of drug sponsors for use with one or more of their prescription drug products. The proposal follows Commissioner Scott Gottlieb’s promise to establish a new approach to FDA’s regulation of digital health tools, but addresses only a subset of such tools.

Scope of the Proposal Under the proposed policy, FDA would regulate prescription-drug-use-related software “output” as drug labeling, rather than as a digital health medical device. The proposal has two important limitations in its scope. First, it distinguishes between prescription drug-use-related software and the output of such software, and focuses on the latter. Prescription drug-use-related software output includes screen displays, audio messages and other materials communicated to the end user (i.e., a patient, caregiver or healthcare professional) of the software.  Second, the proposal applies only to software applications disseminated by or on behalf of drug sponsors for use with their prescription drug products, and does not apply to software applications that may be used with prescription drug products, but marketed separately. FDA considers software output disseminated by or on behalf of a drug sponsor for use with one or more of the sponsor’s prescription drug products as “labeling” under Section 201(m) of the Federal Food, Drug, and Cosmetic Act because FDA regards such output as “accompanying” the drug product.

Categories of Prescription-Drug-Use-Related Software Output The proposal sets forth two categories of software output: “required labeling” and “promotional labeling.” For some software output that is deemed “promotional,” FDA recommends that sponsors obtain advisory comment from FDA’s Office of Prescription Drug Promotion (OPDP) or Advertising and Promotional Labeling Branch (APLB) prior to dissemination. These distinctions would have important regulatory consequences:

1.Output to be regulated as FDA-required labeling would require review and approval as part of a new drug application (NDA), an abbreviated new drug application (ANDA) or a biologics license application (BLA). FDA expects that output would be included in FDA-required labeling in two situations:

  • Substantial evidence exists that demonstrates “an effect on a clinically meaningful outcome” as a result of the use of the software; or
  • The software provides “a function or information that is essential to one or more intended uses of a drug-led, drug-device combination product” and the software is either a device constituent part or an element of a device constituent part

2.Output to be regulated as promotional labeling would require the sponsor to submit the screenshots and other appropriate representations of the proposed output to FDA at the time of initial dissemination along with Form FDA 2253 in the same way that other promotional materials are submitted to FDA. According to FDA, if the output is consistent with FDA-required labeling and does not lead to an increase in potential for harm to health for the user, prior advisory comment is not needed. The proposal provides several examples of software applications that may include output that fits into this category, such as apps with reminder and tracking functionality that generally fall within the policy of enforcement discretion articulated in the guidance document, Mobile Medical Applications, when not distributed by or on behalf of a drug sponsor for use with a prescription drug. Apps already cleared or approved by the Center of Devices and Radiological Health (CDRH) as medical devices that are not part of approved prescription drug-device combination products would also fall within this category.

3.Certain output to be regulated as promotional labeling would be subject to the above dissemination requirements in addition to FDA’s recommendation that the sponsor seek advisory review in advance of the submission. FDA explained that certain prescription-drug-use software output may increase the potential for harm to health, such as output that provides recommendations to patients to make decisions about the drug or disease that would normally be undertaken in consultation with a healthcare provider. If such output is part of a software application that is not already an approved or cleared medical device, FDA recommends that the sponsor avail itself of FDA’s voluntary advisory comment process prior to disseminating the software.

The examples provided include applications that use treatment guidelines to guide patients on how to adjust their medication dose, and applications that provide recommendations to patients on when to seek advice from a healthcare provider based on the patients’ symptoms. These applications seem to fall within CDRH’s proposed policy for Patient Decision Support Software, under which certain low-risk software tools intended for patients or caregivers who are not healthcare professionals would not be actively regulated as devices, when not distributed by or on behalf of a drug sponsor for use with a prescription drug.

Implications of the Proposal

The proposal seeks to “provide drug sponsors the flexibility to innovate and to disseminate prescription drug-use related software without prior FDA approval.” Because the software that produces the output remains subject to regulation as a device component of a combination product, however, the practical effect of excluding output from prior FDA approval is unclear. For example, the notice explains that some applications that are currently considered software as a medical device may be regulated under the proposed framework as both medical device software and output. Prescription drug-use-related software that contains functions that meet the device definition also may be regulated as a device constituent part of a combination product, and information about the software output may be required to be included in FDA-required labeling. If the same software also includes output that is not essential to an indication for the combination product, the output would be considered promotional labeling and would be subject to the promotional labeling dissemination requirements as well.  The proposal poses 10 questions and establishes a docket for comment, which will remain open until January 22, 2019.