Key Takeaways:
- FDA’s recent draft guidance, Regulatory Considerations for Prescription Drug Use Related Software, proposes a regulatory framework for software disseminated by a drug sponsor that supplements or relates to a prescription drug product.
- Prescription Drug Use Related Software (PDURS) may be regulated as a component of a drug’s labeling, as a device, or as a component of a combination product depending on the drug and on the software’s functionality.
- The draft guidance’s discussion on “FDA-required labeling” and “promotional labeling” leaves sponsors with questions regarding how some materials might be regulated for PDURS and other contexts.
After remaining silent on the topic for decades, the Food and Drug Administration (FDA) provided an expansive definition of “promotional labeling” in its recently issued draft guidance document on Regulatory Considerations for Prescription Drug Use Related Software. This latest overture from the FDA could be a sign that potential regulations governing promotional labeling may be on the horizon.
2018 PDURS Federal Register Notice (Request for Comments)
FDA proposed a framework for the regulation of PDURS in a notice and request for comment five years ago. FDA defined PDURS, for purposes of the notice, as “software disseminated by or on behalf of a drug sponsor that accompanies one or more of the sponsor’s prescription drugs, including biological drug products.” Because the software would have to be disseminated 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. FDA cited this output as the regulated component – not the software itself.
FDA reasoned at the time that since the end user output accompanies a specific drug, PDURS should be regulated as labeling. The agency also discussed that PDURS could be subject to device regulation as well and that some uses of PDURS in combination with a drug would constitute a combination product. Furthermore, while third-party software that can be used for multiple drugs would not meet the definition of PDURS, if a drug sponsor licenses or otherwise adopts such software, then it would fall under PDURS.
September 2023 PDURS Draft Guidance – Labeling Definitions and Considerations
Consistent with the 2018 notice and FDA’s policies for the regulation of device software functions, FDA explained in the PDURS draft guidance that it “intends to focus its device regulatory oversight on only those software functions that are devices and whose functionality could pose a risk to a patient’s safety if the device were not to function as intended.” (On a related note, FDA posted a list of frequently asked questions about digital health on its webpage 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 drug labeling authorities to the end-user output of PDURS.
FDA’s recent draft guidance adds a more concrete definition for PDURS and provides general commentary on prescription drug labeling, which raises a few questions that reach beyond the scope of the PDURS guidance. FDA updated the PDURS definition to consist of “software that (1) is disseminated by or on behalf of a drug sponsor and (2) produces an end-user output that supplements, explains, or is otherwise textually related to one or more of the sponsor’s drug products.” FDA did not change the definition for “end user output” or its intention to regulate such output as prescription drug labeling.
The draft guidance, however, elaborates on “prescription drug labeling” by mentioning that FDA “generally recognizes two broad categories of prescription drug labeling: (1) FDA-required labeling and (2) promotional labeling.” FDA defines “required labeling” in the draft guidance as labeling submitted along with a new drug application (NDA), abbreviated new drug application (ANDA), biologics license application (BLA), or as a supplement to any of those applications. Prescribing information (PI), and labeling required under 21 CFR § 201.56 is included under the “FDA-required labeling” category. Any labeling that does not fall under “FDA-required labeling” is considered “promotional labeling” according to the guidance.
This expansive interpretation could subject virtually any communication a sponsor makes about its drug to FDA’s promotional labeling requirements. As the draft guidance explains, a drug sponsor must ensure that a drug’s promotional labeling is truthful and non-misleading, conveys balanced information about the drug’s efficacy and its risks, and discloses material facts about the drug, including facts about the consequences that can result from use of the drug as suggested in a promotional piece.
The draft guidance document outlines some factors FDA will consider when ascertaining whether outputs from PDURS are considered FDA-required or promotional labeling. These factors include (1) whether the software provides a function that is 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 directly transferred from the device constituent part of a combination product.
FDA also discusses the interactivity between PDURS and a drug or drug-device combination product’s prescribing information. A product’s PI may contain discussion regarding PDURS outputs, and in some circumstances the PI may require discussion and explanation of PDURS and how to interpret the end user output. The agency provides two appendices of examples that provide context for some of the factors the agency considers when making determinations regarding labeling disclosures, labeling category, and other regulatory considerations the draft guidance introduces.
FDA-Required v. Promotional Labeling
While the differentiation between “FDA-required" and "promotional” labeling appears for the first time in this draft guidance document, the dichotomy leaves many open questions that the draft guidance does not address. For instance – would a drug or sponsor logo alone transform what would traditionally be 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”? Even though FDA’s regulations require manufacturers to list both product and manufacturer names in multiple contexts, this draft guidance states that when an output mentions 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 both categories and how would 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 baseline definition of “promotion,” and both FDA and Congress have historically avoided defining “advertising” or “promotional labeling.” The FDA takes a bold step by defining “promotional labeling” in this draft guidance document in lieu of promulgating a regulation. Could FDA’s effort to define “promotional labeling” in this context forecast future regulatory developments that would further define “promotional labeling” and other aspects of drug and device advertising and promotion?
FDA has opened a docket for public comments, which are due by December 18, 2023. Foley Hoag is available to address any questions about the draft guidance and provide assistance with comment preparation.
