Background

Since 2009, FDA has been operationalizing the “scientific exchange” safe harbor by way of 1) its 2014 “Revised Draft Guidance for Industry: Distributing Scientific and Medical Publications on Unapproved New Uses-Recommended Practices” often referred to as “Good Reprint Practices,” which permitted companies to disseminate certain publications about unapproved uses, and 2) the 2011 “Draft Guidance for Industry: Responding to Unsolicited Requests for Off-Label Information about Prescription Drugs and Medical Devices,” which described how firms may respond to unsolicited requests for off-label information.

This most recent SIUU guidance, which is an update to the 2014 draft guidance referenced above, expands this informal safe harbor to include proactive dissemination of certain off-label information. Communications that fall within the bounds of the guidance will not be considered evidence of a new intended use. Key differences from the 2014 guidance include:

• More medical products: in addition to human drugs, biologics, and devices, the new guidance also covers animal drugs;

• More materials: in addition to scientific/medical journal articles, scientific/medical reference texts, Clinical Practice Guidelines (CPGs), the new guidance also covers materials from independent clinical practice resources. Importantly, the new guidance also includes firm-generated presentations of scientific information from an accompanying published reprint within the scope of the safe harbor; and

• New evidentiary standard: SIUU information must be “scientifically sound and clinically relevant” (SSCR).

“Firm-generated presentations”

The SIUU guidance broadens the scope of the current safe harbor to include not only dissemination of reprints and CPGs, but also firm-generated presentations of scientific information from an accompanying reprint. FDA’s inclusion of firm-generated presentations of SIUU within the “reprint safe harbor” seems to reflect the agency’s endorsement of certain industry activities, such as post-congress Medical Affairs presentations and the availability of SIUU materials on company-sponsored websites. However, the guidance still leaves open questions regarding presentations based on studies that have not been published in a reprint or endorsed by a CPG – as always, the devil is in the details.

FDA’s core recommendations regarding sources of SIUU information remain the same, in that publications and other references should be published in reputable, peer-reviewed, and independent journals/publishers. Consistent with these general recommendations, FDA recommends that firm-generated presentations should:

• include the reprint and recommended disclosures;

• abide by recommended presentational considerations (for example, avoiding persuasive marketing techniques, remaining separate and distinct from promotional considerations to avoid conflating approved and unapproved uses, and using plain language); and

• avoid implying that the underlying study, analysis, or data represents more than it actually does and/or presenting information out of context.

FDA also suggests that firms be mindful that the media and platforms used to share SIUU communications may prompt unique presentational challenges and considerations (e.g., character-space limitations). Platforms that may limit a firm’s ability to include disclosures should be used to direct HCPs to an SIUU communication, rather than host the communication itself.

“Scientifically sound” and “clinically relevant”

FDA’s guidance introduces a new standard for assessing presentations of off-label information: the source publications underlying SIUU communications should describe studies or analyses which are both scientifically sound and provide clinically relevant information. To meet this standard, scientifically sound studies or analyses should, at minimum, meet generally accepted design or other methodological standards. Statistical robustness, for example, is generally necessary but not sufficient. To qualify as clinically relevant, the studies or analyses should provide information that is pertinent to HCPs engaged in making clinical practice decisions for the care of an individual patient. FDA further notes that “preliminary scientific data” or data from early stage studies will not be considered as clinically relevant information. It remains unclear what the agency considers to be preliminary or early stage studies, except that non-clinical data or analyses alone will not be considered clinically relevant.

For human and animal drugs, the guidance expresses a preference for randomized, double-blind, concurrently-controlled superiority trials. However, other types of well-designed and well-conducted studies may also qualify, including open-label studies, single-arm studies, and epidemiological studies. The inclusion of “analysis” or meta-analyses as source publications also potentially broadens the scope of materials that can serve as source of SIUU communications.

In the device context, the guidance adopts the definition of valid scientific evidence (21 CFR 860.7) to 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 a marketed device as “most likely to be scientifically sound and clinically relevant.”  

The guidance also allows that real world data/real world evidence (RWD/RWE) on medical products may be scientifically sound and clinically relevant depending on the nature of that data.

Key Takeaways:

• Although it states that to does not cover existing policy regarding unsolicited requests, the SIUU guidance appears to significantly narrow the applicability of FDA’s “Draft Guidance for Industry: Responding to Unsolicited Requests for Off-Label Information about Prescription Drugs and Medical Devices”. Because the SIUU guidance appears to endorse certain proactive SIUU communications, the need for reactive communications on off-label uses is limited to responding to questions that arise in a promotional context.

• FDA does not address all forms of publications – implying that those are not covered as “source publications.”

• “Scientifically sound” and “clinically relevant” are defined broadly, which may present challenges predicting the Agency’s interpretation of both.

• The full scope of “persuasive marketing techniques” is unclear and could raise significant issues around use of videos, events with meals, use of social media, and the like. 

Next steps

FDA has arguably broadened the safe harbor, but also introduces new challenges for stakeholders in evaluating the specific language that is appropriate for engaging with HCPs regarding off-label uses.

FDA is accepting comments on the draft guidance through December 26, 2023, under docket number FDA-2008-D-0053. If you have questions on the proposed guidance, labeling requirements more generally, or wish to submit a comment, please contact the authors of this alert or the Hogan Lovells attorney with whom you generally work.