FDA approved drugs and medical devices are often studied further by sponsors and other firms to generate additional scientific information around other potential benefits and uses of those products. Providing the results of this additional scientific activity to health care providers (“HCPs”) has led to enforcement from the U.S. Food and Drug Administration (“FDA), as those additional uses and benefits have not been evaluated by the FDA. If a firm communicates information about unapproved uses of an approved product, it could lead to a determination by FDA that the firm is promoting an unapproved intended use, which could lead to enforcement action for distributing a misbranded or adulterated product. In an effort to provide recommendations on how to avoid FDA enforcement activity when providing the results of this additional scientific activity, FDA recently issued final guidance on how to communicate scientific information on unapproved uses (“SIUU”) of approved or cleared medical products to HCPs while avoiding FDA enforcement action.
The final guidance, once formally implemented by the Office of Management and Budget, outlines FDA’s enforcement policy, ensuring that “firms” providing such communications do so in a manner that is truthful, non-misleading, and includes all necessary information for HCPs to make informed clinical decisions. “Firms” subject to this guidance are those “persons legally responsible for the labeling of medical products,” which broadly applies to all entities in the supply and distribution chain, including sponsors, manufactures, distributors of medical products and licensees of any such entities. As with most FDA guidance, the final guidance represents the current thinking of the agency with regard to its enforcement policy but does not establish any rights for any individual and is not binding on FDA or the public.
FDA states that the guidance is intended to provide reassurance to firms that so long as an SIUU communication is consistent with the recommendations provided in the FDA’s guidance, the FDA “does not intend to use the firm’s dissemination of such communication standing alone as evidence of the firm’s new intended use.”
Ultimately, the guidance seeks to balance two competing public health interests. First, the guidance explains that when a firm chooses to communicate information about unapproved uses of its approved/cleared medical product, such communication, along with other factors, could be evidence of its intended use and therefore relevant to establishing that the firm has distributed a medical product that fails to comply with applicable premarket requirements or is otherwise misbranded or adulterated. Second, in certain circumstances, HCPs may be interested in scientific information about unapproved uses of approved/cleared medical products to inform clinical practice decisions for the care and management of their individual patients.
The guidance contains a variety of recommendations for firms to avoid FDA enforcement actions through a series of Q&As and examples, including recommendations relating to the source publications relied upon, information to include in SIUU communications, and presentational considerations.
- Use of Source Publications in SIUU Communications: The guidance provides that when firms communicate scientific information about unapproved uses of approved or cleared medical products to HCPs, it is crucial that this information be truthful and presented in a manner that supports HCPs’ understanding and evaluation without misleading them about the product’s safety and effectiveness for unapproved uses. The guidance addresses the importance of choosing source publications that are not likely to lead to direct or indirect patient harm when relied upon by HCPs. In pursuit of this outcome, the FDA provides recommendations for the type of source publications to be included by firms in SIUU communications, such as those based on scientifically sound studies and published in peer-reviewed journals. FDA also recommends that texts and materials should be published and distributed independently as medical and educational content. The guidance also recommends that firms take into account existing scientific knowledge to determine whether a source publication is appropriate to include in an SIUU communication, both when initially preparing the communication and at the time of each dissemination of that communication. The FDA provides further guidance to firms considering the inclusion of reprints, clinical practice guidelines (CPGs), scientific or medical reference texts, and materials from digital clinical practice resources in SIUU communications.
- Information to include in SIUU communications: The guidance also outlines specific information that firms should include as part of SIUU communications, including, for example, a statement that the unapproved use(s) of the medical product has not been approved by FDA, a disclosure of the approved uses, and any limitations or warnings from the FDA-required labeling. Additionally, FDA includes several things SIUU communications should not include. For example, SIUU communications should not include any implication that a study, analysis, or underlying data or information represents larger or more-general experience with the medical product than it does. Further, SIUU communications should not present conclusions about the safety or effectiveness of the unapproved use without expressly attributing that statement to the source publication.
- Firm-Generated Presentations: The FDA also discusses presentational considerations that firms should take into account when preparing SIUU communications. FDA recommends that SIUU communications should be separate from promotional materials about approved uses, including making separate web pages to describe SIUU and approved uses, and ensuring emails and in-person conversations involving SIUU and promotion of approved uses are not intermingled. SIUU should also be shared through media that allow for the implementation of the FDA’s recommendations. Firm-generated presentations that use communication techniques to influence HCPs based on elements other than the communication’s scientific content, e.g., jingles, celebrity endorsements, or that pre-judge the benefits of the medical product for individual patients are outside the scope of this guidance, and using those techniques in presentations would not extend obtain the benefit of FDA’s enforcement policy outlined in this guidance.
The FDA does not expect firms to submit SIUU communications to the FDA before being shared with HCPs.
The FDA’s new guidance provides helpful examples of what qualifies and does not qualify as SIUU. This guidance underscores the importance of maintaining the integrity of the premarket review process while supporting informed clinical decision-making. Firms must adhere to the outlined recommendations, including the selection of scientifically sound source publications, the inclusion of mandatory disclosures, and the careful presentation of SIUU communications. It’s essential for firms to understand the implications of this guidance on their communication strategies and ensure compliance to foster trust and transparency in the dissemination of scientific information to HCPs.
Crowell Health Solutions will be monitoring further developments around this guidance and additional guidance in this area, and can assist with any questions about this guidance or the current guidance landscape.