A Door Ajar: FDA's Final SIUU Guidance And Off-Label Communications

By Suzanne Levy Friedman

Drug and device manufacturers have long sought clearer rules for sharing scientific information about unapproved (off-label) uses of their products with health care providers (“HCPs”). In January 2025, FDA delivered — issuing, at long last, a finalized framework ("Communications From Firms to Health Care Providers Regarding Scientific Information on Unapproved Uses of Approved/Cleared Medical Products: Questions and Answers", known as the “SIUU guidance”) that many viewed as a meaningful liberalization.

Among other things, the final guidance for the first time explicitly allows sales and marketing personnel to share off-label scientific information during detailing visits, permits firms to post such content on their websites, and expands the types of evidence that qualify. But a closer look reveals that implementing the guidance’s safe harbor — compliantly and at scale — is quite demanding. Benefitting from this policy will require genuine attention to detail and a solid understanding of what it does, and does not, change.

The Crux of the Issue

Under the Federal Food, Drug, and Cosmetic Act (“FDCA”), manufacturers generally cannot promote their products for uses that FDA has not approved or cleared. Yet physicians are free to prescribe authorized products for any use they deem clinically appropriate — and often rely on off-label data in doing so, particularly where approved options are limited or nonexistent.

This creates a longstanding tension: HCPs need scientific information to make good clinical decisions, and manufacturers often possess the most comprehensive data on how their products perform across populations and settings. But allowing manufacturers to communicate freely about off-label uses risks blurring the line between scientific exchange and marketing, potentially exposing patients to treatments whose safety and efficacy remain unproven.

How We Got Here

FDA has been iterating on the SIUU framework for nearly three decades. Congress first addressed the issue in 1997 through the Food and Drug Administration Modernization Act (FDAMA), which created a safe harbor allowing manufacturers to share medical or scientific articles about unapproved uses without that act alone constituting evidence of intent to promote these uses. But those provisions sunset in 2006. A series of First Amendment challenges, beginning with Washington Legal Foundation v. Henney in 2000, further complicated FDA’s ability to restrict the dissemination of truthful off-label information.

In 2009, FDA issued its “Good Reprints” guidance, outlining conditions for distributing peer-reviewed reprints and reference publications about off-label uses. A 2014 revision broadened coverage to include clinical practice guidelines (CPGs) and individual sections of larger publications. Then, in October 2023, a new draft guidance made more significant changes:

1. Allowed manufacturers to share “firm-generated presentations” of scientific information from an accompanying reprint that satisfies the safe harbor;
2. Limited dissemination to source publications describing studies or analyses that are “scientifically sound” and provide “clinically relevant information";
3. Cautioned against “persuasive marketing techniques” — methods that influence prescribing based on factors other than scientific content. FDA stressed that the safe harbor is limited to non-promotional dissemination so as to preclude its use to circumvent the premarket review process.

The 2025 final SIUU guidance was published in the last days of the Biden administration, and remains in effect — making it the operative framework that manufacturers must work with today.

Practical Impact

The 2025 SIUU guidance has several important clarifications and implications that may help limit the regulatory burden on manufacturers and streamline compliance practices, if implemented carefully:

• A source publication can serve as the basis for SIUU if it is “scientifically sound”; and multiple evidence types may qualify for such designation.

“Clinically relevant” — previously criticized as subjective and unduly restrictive — has been removed from the standard defining eligible source publications. Additionally, certain early-stage clinical data and other study types may qualify as scientifically sound when properly designed and conducted. This opens the door to sharing information gathered across more stages of product development and in more contexts. But FDA still cautions that materials must “appropriately present all the information necessary for HCPs to understand and evaluate the strengths and weaknesses, validity, and clinical utility” of the information — so clinical relevance remains a practical guardrail even if no longer a formal gate.

• Firm-generated presentations may be based on all types of permitted source publications.

The narrower 2023 framework limited such presentations to being based on journal reprints.

• SIUU content may be shared on firm websites.

This explicit recognition resolves a longstanding regulatory uncertainty. FDA recommends that such content be located on a separate web page from, and not linked to, promotional content. Firms should, however, take care that content selection does not give a misleading impression of the product or unapproved use in question, as this would violate the underlying statute.

• SIUU content can now be shared by sales/marketing personnel.

The guidance acknowledges that one person or team might share both promotional and non-promotional content, if they are properly trained and are able to direct questions to those best qualified to respond. In effect, this means that sales representatives may share off-label information with customers or prospects during detailing visits — as long as there is meaningful separation from promotion of on-label uses.

• Firm-generated presentations that employ certain communication methods conflate the sharing of scientific information and the promotion of an unapproved use.

Celebrity endorsements, emotional appeals unrelated to scientific content, promotional taglines, jingles, gifts, premium offers, and certain “calls to value” (which pair a call to action with a value proposition, such as “Click here to XX”) are specified to exceed the safe harbor.

• Several restrictions pertinent to FDA’s 2011 policy on responding to unsolicited requests about off-label information are now inapplicable, given the broader scope of permissible proactive communications with HCPs.

Compliance processes should likely be updated to properly align with both current policies. Importantly, though, the 2011 draft guidance — and associated limitations — remain relevant for specific situations:

• Where off-label information is sought in promotional contexts;
• Where the information requested exceeds what could be a proper SIUU communication (e.g., questions about products with no FDA authorization); and
• Where the question/request comes from a patient or consumer.

Lessons about Application

The final SIUU guidance ends 16 years of industry reliance on draft guidance that could have been withdrawn or revised at any point. In that sense alone, it provides a measure of regulatory certainty. But certainty about what the rules say is not the same as certainty about how FDA will apply them. Recent enforcement activity offers early indicators worth examining.

No companies have been publicly cited for violating the 2025 guidance as such. That is unsurprising: FDA enforcement actions cite the underlying statute — misbranding via promotion of a new intended use — rather than non-compliance with an enforcement discretion policy. So the relevant enforcement signals are indirect, but they are real.

FDA's elevated enforcement activity in late 2025 and early 2026 concretizes the risk companies face upon sharing off-label information outside of the guidance’s safe harbor. On the drug side, recent citations involve false or misleading presentations of endpoints based on data unlikely to qualify as “scientifically sound.” On the device side, several Warning Letters allege promotion exceeding the scope of an existing clearance or 510(k)-exempt classification — content that falls outside the SIUU safe harbor regardless of scientific merit.

One September 2025 Warning Letter is particularly instructive. FDA cited a firm for promoting laser devices as treating conditions not addressed by standard medical care, highlighting a case study that attributed curing of a patient’s peripheral neuropathy to the company’s device. Though the letter does not reference the SIUU guidance directly, the implication tracks its language: FDA does not consider a singular case study without documented background to constitute “scientifically sound” evidence.

Where Do We Go from Here?

Companies wishing to benefit from the final SIUU policy should start with two steps: ensure its criteria are consistently reflected in their compliance infrastructure, and conduct a gap analysis of existing SIUU-like communications against the guidance’s specific requirements. Three areas deserve particular attention:

• The required disclosures must each be integrated "clearly and prominently" into the communication. That means careful attention to font, graphic design, and audio parameters (if applicable). While HCPs may be used to seeing disclaimers and evaluating the underlying clinical content on its own merits, the multitude and extent of caveats required per the policy may feel overwhelming to brand personnel accustomed to traditional marketing. Nevertheless, they are non-negotiable.
• Platform selection matters. A communication that otherwise satisfies the guidance but is delivered via a channel where all requisite disclosures cannot be accommodated (such as character-limited media) is not compliant SIUU.
• Companies — particularly those wishing to involve non-Medical Affairs personnel in in-person SIUU distribution — must develop adequate training programs for professionals engaged in these activities. They should be prepared to rationalize their interpretation of the “specialized training” called for by FDA; robust documentation of training content and attendees will be critical to that end.

The policy finalized in 2025 is still more restrictive than many manufacturers would like, and it is arduous to implement — but it is also the clearest framework the industry has ever had. For the first time, FDA appears to genuinely acknowledge manufacturers’ need — and intent — to share SIUU materials, and to be aiming to balance its public health mandate with feasible practices. Manufacturers who invest the effort upfront to understand the boundaries drawn can operationalize the policy to the benefit of their business and clinical knowledge. Those who treat the guidance as a green light, without that investment, should not expect the safe harbor to protect them.

About The Author:

Suzanne Levy Friedman is a partner in Honigman LLP’s Regulatory Department in the Washington, D.C. office, where she counsels companies within the Medtech and digital health industries on navigating the complexities of U.S. Food and Drug Administration (FDA) medical device regulation.

Suzanne's practice focuses on strategically guiding clients in a wide range of activities across the life cycle of their products, including preparing regulatory submissions for new device clearance and approval, advising on the lawful promotion of devices and non-device software products, and assisting with post-market compliance.