(In)Box Full of Letters: OPDP Published Untitled Letter Regarding Emails to Healthcare Professionals

Key Takeaways

• OPDP continues to scrutinize promotional messaging to healthcare professionals (“HCPs”), despite recent enforcement focusing on direct-to-consumer (“DTC”) advertising.
• OPDP’s recent Untitled Letter highlights key promotional compliance risks, including implied off-label use, incomplete risk disclosures, and inadequate presentation of indication and safety information that may create a misleading net impression.
• Life sciences companies should re-evaluate email campaigns to HCPs, Important Safety Information, and promotional review processes to ensure approved indications, fair balance requirements, and risk disclosures are communicated clearly and prominently.

Wilco’s 1995 song “Box Full of Letters” came to mind when we reviewed a recent Untitled Letter from the Food and Drug Administration’s Office of Prescription Drug Promotion (“OPDP”) regarding emails to HCPs. We have written extensively about OPDP’s 2026 enforcement letters, which have largely targeted DTC promotional materials. However, this recent letter reminds us that OPDP’s scrutiny extends well beyond DTC advertising.

Highlights From the Untitled Letter

The Untitled Letter addresses promotional emails sent to HCPs regarding pediatric and adult uses of a gastrointestinal prescription drug product. OPDP identified several violations.

• OPDP determined that the emails implied an unapproved use, specifically, that “because of overlapping symptoms of [disease], [product] can be used to treat [other conditions] … when this is not the case.” By suggesting utility beyond the approved indication based on symptom overlap, the materials conveyed an expanded scope of use beyond the approved labeling.
• The emails did not provide the full indication in the body text. OPDP noted that while the full indication was provided in the Important Safety Information (“ISI”) section at the bottom of the email, it was “presented in small plain font, after intervening text and graphics and/or colors. Therefore, this is not sufficient to mitigate the misleading impression.” OPDP has consistently emphasized that qualifying language buried or deemphasized in formatting does not cure a misleading front-end message.
• OPDP found that the emails omitted certain risk information from the ISI, rendering the safety disclosures incomplete.
• FDA challenged the sequencing of risk information, noting that risks “do not appear in a sequence that discloses risk information in order of severity” and, as a result, minimized certain risks. Specifically, the emails presented adverse reaction information from the prescribing information before a risk contained in the Precautions section, “thereby framing the subsequent risk information as less serious.”

AGG Observations

• Recent OPDP focus has been on DTC promotion, but this Untitled Letter targets emails to HCPs. This is notable because, generally, both HCP communications and email communications have received comparatively less attention in recent enforcement actions. Companies should not assume that HCP-directed pieces face a lower level of regulatory scrutiny.
• In our participation in companies’ Medical, Legal, and Regulatory (“MLR”) or Promotional Review Committee (“PRC”) processes, we frequently hear, particularly for short pieces, that “the full indication is in the ISI below,” and that a shortened indication in the main text is ameliorated by the full indication below. Not necessarily. OPDP is reminding industry that if the text font and prominence are such that the ISI information is minimized in comparison to the promotional content, the overall messaging can be problematic and potentially misleading. Net impression governs, and a technically complete but functionally unperceived disclosure does not satisfy fair balance requirements.
• In our experience with MLRs and PRCs, once an ISI is prepared, companies are often reluctant to revisit and revise it unless the label itself has been revised. The ISI becomes gospel. While we understand the desire for consistency, cost savings, and efficiency, we caution against never re-reviewing the ISI periodically. An ISI might have been written years ago by someone no longer at the company. It is important to review an ISI periodically to ensure it is current, thorough, and presented in a manner that discloses important risk information appropriately.
• We also see claims in PRCs and MLRs that highlight conditions sharing symptoms with the indicated disease or contributing factors of the disease, implying treatment of those conditions or associated symptoms. These types of claims can be misleading and imply uses beyond the approved indication. OPDP emphasizes here that the approved indication must be clear and that promotional materials must track the full specificity of the approved indication.

This Untitled Letter is a reminder that OPDP’s enforcement reach extends beyond DTC advertising and into HCP-directed communications, including email. The agency continues to apply its net impression framework, evaluating not only individual statements, but the overall takeaway of the communication. Similar to the letters piling up in Wilco’s box, OPDP’s enforcement correspondence shows no signs of slowing down.

For guidance on these issues, please contact a member of AGG’s Food & Drug team.