FDA Finalizes Its SIUU Guidance: An Analysis of the Key Changes From the 2023 Draft Guidance

At the start of the new year, the U.S. Food and Drug Administration (FDA) finalized its October 2023 guidance (the Final SIUU Guidance) on scientific information on unapproved use(s) of approved/cleared medical product communications (SIUU communications).¹ The Final SIUU Guidance outlines FDA’s policy on firm-initiated communications of scientific information of unapproved use(s) of approved medical products to health care providers and provides the contours of the agency’s enforcement discretion policy with respect to these communications. For instance, the enforcement discretion policy does not apply to communications regarding investigational compounds unapproved for any use nor does it apply to off-label communications with patients or lay persons. The Final SIUU Guidance also reiterates FDA’s view that the described enforcement discretion policy is consistent with advancing substantial governmental interests such as preserving the incentives for premarket review. The essence of the October 2023 draft guidance remains, including the concept of scientifically sound source publications, what firms should include as a part of SIUU communications, and FDA’s specific recommendations for sharing clinical practice guidelines (CPGs). Still, there are several changes in the Final SIUU Guidance worth highlighting.

Clarification of Source Publication Standards. The Final SIUU Guidance adds greater detail about scientific soundness of source publications for human and animal drugs and medical devices, dropping the term “clinically relevant” with preference for scientifically sound. FDA notes that scientific soundness follows generally accepted scientific principles for design and methodology. For human and animal drugs, concurrently controlled superiority trials are considered the “most rigorous design” and therefore the most likely to be considered scientifically sound, though other studies can also qualify as long as they are adequately designed and conducted — which the agency equates to data sources being reliable and relevant, protocols and statistical analysis plans having been finalized prior to conducting the analyses, and careful monitoring and maintenance of data integrity. FDA provides several examples of the types of studies that it may consider scientifically sound, including early-phase randomized trials, single-arm or externally controlled trials, and non-interventional (observational) studies.² For devices, scientifically sound studies include well-controlled investigations, partially controlled studies, studies and objective trials without matched controls, well-documented case histories conducted by qualified experts, and reports of significant human experience with marketed devices.³ Notably, FDA removed the specific statement that said real-world data and real-word evidence could be scientifically sound and clinically relevant, and instead included a footnote pointing readers to FDA’s more general thinking on the use of real-world data to generate real-world evidence.

FDA also encourages firms to take into account existing scientific knowledge to determine whether a source publication is appropriate to include in SIUU communications and recommends that firms ensure that the source publication aligns with the publication prespecified hypothesis. Additionally, likely in response to stakeholder comments, the Final SIUU Guidance did not preserve language from the draft guidance dissuading companies from relying on scientific data generated in the “early stages” of product development.

Enforcement Policy Clarifications. Perhaps in anticipation of ongoing criticism of the agency’s historical approach to enforcement against off-label promotion, and clearly mindful of the First Amendment framework, the Final SIUU Guidance includes additional context on the policy underpinnings of the enforcement discretion policy described in the guidance. This includes a “reassurance to firms” whose communications conform to the Final SIUU Guidance approach that such communications alone will not be used to establish a new intended use by FDA.⁴ Rather, the focus of FDA’s enforcement effort on manufacturer-initiated or -sponsored educational or scientific communications continues to be whether they are truthful and non-misleading. Consistent with other scientific exchange policies, FDA also notes that communications conforming to the guidance do not need to be submitted to the agency upon first use.⁵ Helpfully, FDA references the preamble statements in the 2021 revisions to the intended use rule and this Final SIUU Guidance to demonstrate how manufacturers can engage in truthful, non-misleading scientific exchange activities without risk of establishing a new intended use:

Accordingly, a firm would not be regarded as intending an unapproved use for its approved or cleared medical product based solely on the combination of (1) the firm’s knowledge that such medical product is being prescribed or used by HCPs for an unapproved use and (2) the firm’s sharing of SIUU communication(s) about that unapproved use consistent with the recommendations in this guidance.

FDA acknowledges that a failure of a communication to conform to the guardrails outlined in the Final SIUU Guidance does not automatically establish that such a communication may be used as evidence of intended use. That said, FDA notes that the Final SIUU Guidance policy does not affect “a firm’s existing obligations under [FDA regulations] to update FDA-required labeling to accurately reflect what is known about the safety profile of the drug.”⁶

Abandonment of “Persuasive Marketing Techniques” in Favor of Examples. The draft guidance took issue with the use of “persuasive marketing techniques,” noting that combining such techniques with otherwise truthful scientific or educational communications would be inconsistent with the enforcement policy set forth by FDA. The parameters of the term “persuasive marketing” were not well-defined and were a focus of industry feedback in the draft guidance. The Final SIUU Guidance has jettisoned the term completely, instead relying on examples of the kinds of communications FDA would view as “correct” and “incorrect” under the new SIUU approach.

“Correct” communications under the new SIUU approach include:

• Truthful and Non-Misleading Firm-Generated Presentations. In the Final SIUU Guidance, FDA clarifies that firm-generated presentations can include scientific information from any source publications (published reprints and published clinical reference resources, including CPGs, reference texts, and materials from digital clinical practice resources). Firms should limit their presentations to the scientific information in the sources, provide the source publication(s) with the firm-generated presentation, and should include appropriate disclosures, such as “This presentation was developed by FIRM X.”⁷ Further, FDA recommends that firm-generated presentations include all material information related to the presentation. For example, if a presentation includes study results, it should also include all material aspects and limitations of the study design, methodology, and all results necessary to interpret the presented information.⁸

On the other hand, firm-generated presentations which are “incorrect” under the new SIUU approach include:

• General and Inconsistent Representations. Firm-generated presentations should not imply that the study or underlying data represent a more general experience with the medical product than it actually does. FDA also warns against presentations which make representations about the medical product’s safety and effectiveness inconsistent with the source publication. Similarly, presentation information should not be presented out of context.⁹
• Unsupported Representations or Conclusions. Firm-generated presentations should not include representations or conclusions that are unsupported by the source publication, this includes “excerpts, quotes, paraphrases, conclusions,” and statistical analyses that indicate clinical significance. Statements which are expressly attributed to the source publication must include follow-up statements that identify contributors to the source publication.¹⁰
• Distorted Presentational Elements. Firm-generated presentations should not use elements like graphs, tables, textual features, or other design elements that distract attention from unfavorable information to only emphasize positive information.¹¹
• Communications That Influence Decisions Based on Elements Other Than the Communication’s Substance. FDA notes that techniques which use, “celebrity endorsements, emotional appeals unrelated to the scientific content, gifts, promotional tag lines, jingles, and premium offers”¹² do not fall in the scope of SIUU communications. FDA cites to research which shows that these types of communication are effective at influencing the attitudes and behaviors of health care professionals unrelated to the quality of information presented.
• Calls To Value That Prejudge Benefits. According to FDA, a “call to value” is a communication technique that includes both a call to action and a value proposition that explains to the reader how the action will translate for them. Calls to value that prejudge the benefit(s) of a medical product for individual patients will not fall within the enforcement policy outlined in the Final SIUU Guidance. Per FDA, “Call FIRM X now for more information on [Medical product X] — it’s the best option for your difficult-to-treat patients!” and “Click here to start improving your patients’ lives today.”¹³ are impermissible “calls to value” in SIUU communications because they prejudge the value to the reader. On the other hand, “Click here to access the full article for free!” or “Read now to learn more about this new data on Medical product X,”¹⁴ which do not prejudge the medical product, would not cause a firm-generated presentation to fall outside the enforcement policy in the Final SIUU Guidance.

Clarification of Presentational Considerations. In the Final SIUU Guidance, FDA revised the discussion of presentational considerations to only state that SIUU communications should be separate from promotional communications for approved uses. By contrast, the draft guidance would have required SIUU communications to be separate and distinct from promotional communications. FDA notes that an appropriate separation minimizes the risk of health care provider conclusions that the firm’s medical product has been demonstrated to be safe and effective for all presented uses, including the unapproved use(s). To further illustrate this point, FDA added examples related to sharing SIUU information online and with health care providers at in-person visits:

• Online Information. If SIUU communications are shared online to health care providers through websites, FDA recommends that SIUU communications be on a separate webpage from the web page that hosts promotional information about approved use(s). Additionally, FDA encourages firms “not [to] include direct links from web pages that host promotional communications about approved uses to web pages that host SIUU communications.”¹⁵
• In-Person Visits. Firm representatives who deliver SIUU communications to health care providers during in-person visits should clearly separate SIUU communications from promotional communications about approved use(s) of the firm’s medical product.¹⁶ SIUU communication should be presented through, “clear and prominent presentation of the disclosures.”¹⁷

The Final SIUU Guidance reflects FDA’s latest thinking on its planned enforcement policy for certain off-label scientific and educational communications. FDA’s intended use regulations have generated controversy over the years, and it is possible that a new administration could reevaluate the regulatory underpinnings of the restrictions on manufacturer communications articulated in the Final SIUU Guidance. That said, the Final SIUU Guidance confirms a more permissive approach to scientific exchange communications than has historically been articulated by the agency in the past, and it does present new, measured opportunities for proactive communication of truthful, non-misleading off-label information.

If manufacturers have questions about how the Final SIUU Guidance applies to their own specific circumstances, please do not hesitate to connect with any of the authors or your usual Arnold & Porter contact.

© Arnold & Porter Kaye Scholer LLP 2025 All Rights Reserved. This Advisory is intended to be a general summary of the law and does not constitute legal advice. You should consult with counsel to determine applicable legal requirements in a specific fact situation.