Key learning points:
- The recent FDA draft guidance, Regulatory considerations for software related to the use of prescription drugsproposes a regulatory framework for software distributed by a drug sponsor that supplements or relates to a prescription drug.
- Prescription drug use software (PDURS) may be regulated as part of a drug’s labeling, as a device, or as part of a combination product, depending on the drug and the functionality of the software.
- The draft guidance’s discussion of “FDA required labeling” and “promotional labeling” leaves sponsors with questions about how some materials might be regulated for PDURS and other contexts.
After decades of silence on the subject, the Food and Drug Administration (FDA) provided an expanded definition of “promotional labeling” in its recently issued draft guidance on regulatory considerations for software related to the use of prescription drugs. This latest overture from the FDA could be a sign that potential promotional labeling regulations are on the horizon.
PDURS Federal Register Notice 2018 (request for comments)
The FDA proposed a framework for regulating PDURS in a notice and request for comment five years ago. The FDA defined PDURS for the purposes of the notice as “software distributed by or on behalf of a drug sponsor that accompanies one or more of the sponsor’s prescription drugs, including biologic drug products.” Because the software would have to be distributed by or on behalf of the drug sponsor to qualify as PDURS, the framework would not apply to third-party developers of software for use with prescription drugs. The output of PDURS would be the material presented to an end user of the software. End users include patients, caregivers, and healthcare professionals. The FDA called this output the regulated component – not the software itself.
The FDA reasoned at the time that since the end-user output is associated with a specific drug, PDURS should be regulated as labeling. The agency also discussed that PDURS could also be subject to device regulation and that some uses of PDURS in combination with a drug would constitute a combination product. In addition, third-party software that can be used across multiple drug products would not meet the definition of PDURS, but if a drug sponsor licenses or otherwise adopts such software, it would fall under PDURS.
September 2023 PDURS draft guidance – Labeling definitions and considerations
In accordance with the 2018 Notice and the FDA’s Policy for the Regulation of Device Software Functions, the FDA explained in the PDURS draft guidance that it “intends to focus its regulatory oversight of devices only on those software functions that are devices and of which functionality could pose a risk to patient safety if the device did not function as intended.” (In a related note, the FDA posted a list of frequently asked questions about digital health on its web page a few days after releasing the PDURS draft guidance.) Regardless of whether the software itself is regulated as a device, the draft guidance focuses on the application of the drug labeling authorities on the end-user output of PDURS.
The FDA’s recent draft guidelines add a more concrete definition for PDURS and provide general commentary on prescription drug labeling, raising a number of questions that extend beyond the scope of the PDURS guidelines. The FDA updated the PDURS definition to include “software that (1) is distributed by or on behalf of a drug sponsor and (2) produces end-user output that supplements, explains, or is otherwise textually related to a or more of the sponsor’s drugs.” The FDA has not changed the definition of “end-user output” or its intention to regulate such output, such as prescription drug labeling.
However, the draft guidance elaborates on “prescription drug labeling” by stating that the FDA “generally recognizes two broad categories of prescription drug labeling: (1) FDA-required labeling and (2) promotional labeling. ” The FDA defines “required labeling” in the draft guidance as labeling that is submitted with a new drug application (NDA), an abbreviated new drug application (ANDA), a biologic drug licensing application (BLA), or in addition on one of these requests. Prescribing information (PI) and labeling required under 21 CFR § 201.56 are included in the “FDA Required Labeling” category. Any labeling that does not fall under “FDA-required labeling” is considered “promotional labeling” under the guidelines.
This expansive interpretation could subject virtually every communication a sponsor makes about its drug to the FDA’s promotional labeling requirements. As the draft guidance explains, a sponsor of a drug must ensure that a drug’s promotional labeling is truthful and not misleading, contains balanced information about the drug’s efficacy and risks, and discloses material facts about the drug , including facts about the consequences that may arise from it. of the use of the drug as proposed in a promotional piece.
The draft guidance outlines some of the factors that FDA will consider in determining whether PDURS results are considered FDA-required or promotional labeling. These factors include (1) whether the software provides a function essential to the safe and effective use of the product, (2) whether evidence is provided to support a clinical benefit when the software is used, and (3) whether the software relies on data transferred directly from the device that is part of a combination product.
The FDA also discusses the interactivity between PDURS and the prescribing information of a drug or combination product. A product’s PI may include discussion of PDURS output, and in some circumstances the PI may require discussion and explanation of PDURS and how to interpret end-user output. The agency provides two appendices with examples that provide context for some of the factors the agency considers when making decisions regarding labeling disclosure, labeling category, and other regulatory considerations introduced in the draft guidance.
FDA requirement versus promotional labeling
Although the distinction between “FDA requirement” and “promotional” labeling appears for the first time in this draft guidance, the dichotomy leaves many open questions that are not addressed in the draft guidance. For example, would a drug or sponsor logo alone turn what is traditionally considered “FDA-required” labeling into “promotional” labeling? Would non-promotional, scientific information be considered “promotional” under the draft guidance since it is not “FDA required”? Although FDA regulations require manufacturers to include both product and manufacturer names in multiple contexts, this draft guidance states that when an output includes a product name, that output would be considered “promotional labeling.” Could other “required” language become “promotional,” and in what contexts? Could product names and other required information fit under either category and how would the FDA distinguish between them? The agency should address these and other questions, including the applicability of the labeling categories beyond this draft guidance, when finalizing the PDURS guidance.
Notably missing from the draft guidance is a basic definition of “promotion,” and both the FDA and Congress have historically avoided defining “advertising” or “promotional labeling.” The FDA is taking a bold step by defining “promotional labeling” in this draft guidance, rather than promulgating a regulation. Could the FDA’s attempt to define “promotional labeling” in this context foreshadow future regulatory developments that would further define “promotional labeling” and other aspects of drug and device advertising and promotion?
The FDA has opened a docket for public comments, which are due by December 18, 2023. Foley Hoag is available to answer any questions about the draft guidelines and provide assistance in preparing comments.