Medical Science Liaisons (MSLs) play a central role in facilitating the exchange of scientific and clinical information with healthcare professionals (HCPs). Within a continuously evolving regulatory landscape, it is essential that MSL engagement, related to unapproved uses of approved or cleared medical products, aligns with the appropriate FDA framework governing communications.
Two key FDA guidance documents shape expectations: (1) the January 2025 Final Guidance on Communications from Firms to Health Care Providers Regarding Scientific Information on Unapproved Uses (SIUU) and (2) the 2011 Draft Guidance on Responding to Unsolicited Requests for Off-Label Information. Which guidance applies and the regulatory expectations that follow depend on how the interaction is initiated and how the scientific information is delivered.
The 2025 SIUU guidance covers proactive, firm-initiated scientific communications, including the distribution of published source materials or firm-generated summaries derived from those materials. The 2011 Unsolicited Requests guidance covers reactive, HCP-initiated inquiries, where the firm provides scientific information only after receiving a bona fide, unsolicited question.
These two pathways differ in their initiation, evidence requirements, and mechanisms of communication. Below are five critical distinctions MSLs must understand to engage compliantly and credibly.
Proactive SIUU vs. Reactive Unsolicited Requests
Scientific engagement by MSLs falls into two distinct regulatory pathways depending on who initiates the interaction and what type of information is being shared. These pathways—SIUU and Unsolicited Scientific Requests—serve different purposes but work together to support responsible, evidence‑based scientific exchange.
- 1. Proactive vs. Reactive Engagement
Who initiates the conversation determines the cascade of regulatory guidelines that follow.
When the company initiates communication—for example, an MSL proactively shares a peer‑reviewed reprint or a firm‑generated summary on an unapproved use—SIUU guidance applies.
In contrast, unsolicited scientific exchange applies when an HCP asks first. For example, a clinician approaches an MSL at a congress booth and asks an off‑label question.
This key, preliminary difference drives all other regulatory expectations thereafter
- Published vs. Flexible Evidence Requirements
How the conversation is initiated determines the evidence an MSL can rely on.
Under SIUU, evidence must come from published scientific sources (i.e., peer‑reviewed articles, clinical practice guidelines, reference texts, or digital clinical resources). This ensures proactive communication is fully anchored in established, peer‑reviewed evidence.
While SIUU prohibits the use of unpublished data or data on file, the unsolicited request pathway allows more tailored, scientific depth for reactive requests. Responses may incorporate a broader range of data if needed to directly answer the question, including case‑by‑case use of unpublished data handled through medical information processes.
- Proactive Distribution vs. Controlled, Tailored Responses
The expected format of communication also varies. In both cases, the tone must remain scientific and balanced.
SIUU communications may include proactive distribution of reprints, clinical guidelines, or firm-generated summaries that clearly separate scientific content from promotional materials.
Bespoke answers tailored to HCP inquiry are only permitted by unsolicited exchanges, which involve controlled, individualized responses (i.e., medical information letter, email follow‑up, or private discussion) strictly addressing the specific question asked.
Understanding these boundaries helps MSLs maintain scientific credibility while reducing the risk of inadvertently crossing into noncompliant communication.
- Public vs. Nonpublic Settings
How the conversation begins also affects how and where it must proceed.
SIUU materials can be proactively provided in appropriate HCP-focused settings, such as at a congress booth or during scheduled scientific engagements.
When an unsolicited request is made in a public forum (e.g., social media or during a public Q&A), MSLs must acknowledge the question briefly and redirect the individual to a private channel before responding in full to prevent detailed off-label information from being publicly disseminated.
- Enforcement Protections and Documentation Standards
Though each pathway offers regulatory clarity, FDA expectations for documentation differ to protect both the integrity of scientific exchange and the organization’s compliance posture.
Under circumstances where SIUU guidelines are adhered to, the FDA states it does not intend to treat the communication alone as evidence of a new intended use, given the information is truthful, balanced, and sourced appropriately.
For unsolicited requests, the FDA emphasizes the importance of documentation to verify the truly unsolicited nature of the request and adherence to non-promotional, scientifically grounded communication standards.
What This Means for MSL Practice
In today’s environment, MSLs must navigate two contrasting but complementary types of scientific exchange:
- SIUU = Proactive, published‑evidence‑based, firm-initiated communication
- Unsolicited Requests = Reactive, HCP-driven, tailored scientific responses
Together, these pathways protect organizational integrity and dictate how meaningful scientific support can (and should) be provided. It is essential for MSLs to remain knowledgeable of these evolving guidelines to maintain a compliant, transparent, and intentional approach to unapproved use communications.
References:
FDA SIUU guidance page • Federal Register notice for SIUU (Jan 7, 2025) • King & Spalding summary of SIUU changes • FDA Unsolicited Requests (draft, Dec 2011) – FDA page / PDF
About the authors:
Susan Giacalone, MSN, BCMAS, BC-MSL, SVP Medical Deployment, EVERSANA
Beth Giblin, Pharm.D., Head, Field Medical Affairs for PRECIGEN, contracted exclusively by EVERSANA
Amber Svardal, MSN, RN, OCN, Director, Medical Excellence & Sr. MSL for PRECIGEN- contracted exclusively by EVERSANA
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