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.  

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Photo of Linda Malek Linda Malek

Linda Malek is a partner in Crowell’s Health Care and Privacy & Cybersecurity Groups, where she advises a broad array of health care and life sciences clients on compliance with federal, state, and international law governing clinical research, data privacy, cybersecurity, and fraud

Linda Malek is a partner in Crowell’s Health Care and Privacy & Cybersecurity Groups, where she advises a broad array of health care and life sciences clients on compliance with federal, state, and international law governing clinical research, data privacy, cybersecurity, and fraud and abuse. Her clients include national hospitals systems and academic medical centers, genetic and biotechnology companies, pharmaceutical companies, medical device companies, financial institutions involved in healthcare services, research foundations and international scientific organizations.

In the healthcare context, Linda is particularly focused on regulatory compliance issues related to clinical research and clinical trials. She creates and implements comprehensive policies governing the conduct of research involving human subjects, and advises clients on human subject research compliance issues. Linda also counsels on legal issues related to conducting secondary research on existing data repositories and tissue banks, including on data privacy and informed consent issues related to the ability to conduct future research. She has experience advising clients on a wide variety of research areas, including biologics, pharmacogenomics, translational research, secondary research, tissue banking, and data repositories. Linda also advises clients in general health care matters related to fraud and abuse, including issues under the Stark laws and federal and state anti-kickback statutes. Her work includes structuring complex transactions in compliance with such laws, assisting in the creation of internal compliance programs, and advising on issues related to the False Claims Act.

Photo of Jason Johnson Jason Johnson

Jason Johnson is a partner in Crowell’s Health Care and Privacy & Cybersecurity Groups, where he draws on his experience as a former research scientist to advise clients on complex compliance, legal, regulatory, and transactional matters. He helps clients in the health care

Jason Johnson is a partner in Crowell’s Health Care and Privacy & Cybersecurity Groups, where he draws on his experience as a former research scientist to advise clients on complex compliance, legal, regulatory, and transactional matters. He helps clients in the health care and life sciences industries navigate data privacy and cybersecurity issues under U.S. and European law. He also offers strategic insights to assist clients with product development, marketing, clinical research, and other core business initiatives.

Jason is well-versed on even the most complicated regulatory challenges that his clients face. As a former research scientist in academic and pharmaceutical settings, as well as a clinical research monitor who trained physicians, Jason knows the rules firsthand. He employs this knowledge to assist clients with the full range of issues that arise in the research and development process, including drafting and negotiating research, clinical trial, licensing, and manufacturing agreements; intellectual property and technology transfer issues; collection, transfer and sharing of data, including patient registries and bio-repositories; and advising clients on mergers and acquisitions and related transactions. Jason’s clients in this area include academic medical centers, healthcare technology companies, emerging to late stage biotechnology companies, pharmaceutical and medical device companies, and other health care and research organizations.

Photo of Stephen Holland Stephen Holland

Stephen Holland is a senior counsel in Crowell & Moring’s Government Affairs Group, where he leverages his extensive experience advising members of Congress and their staff as a policy advisor and attorney active in health care legislation. Stephen has been responsible for crafting

Stephen Holland is a senior counsel in Crowell & Moring’s Government Affairs Group, where he leverages his extensive experience advising members of Congress and their staff as a policy advisor and attorney active in health care legislation. Stephen has been responsible for crafting dozens of provisions in law to improve food, drug, and medical device innovation and regulation at the Food and Drug Administration (FDA), health coverage and access, public health communication and coordination, prescription drug affordability, and emergency preparedness and response.

Prior to joining Crowell, Stephen served in senior policy roles in the U.S. House of Representatives for over 10 years. Most recently, Stephen spent five years on the Energy and Commerce Committee staff under the leadership of Ranking Member and former Chairman Frank Pallone of New Jersey.  On the Committee staff, he was responsible for legislative action related to numerous agencies and programs, including the FDA, the Biomedical Advanced Research and Development Authority (BARDA), and the 340B drug program. Notably, his work on the Committee included leading negotiations and drafting of the Food and Drug Omnibus Reform Act of 2022 (FDORA), a package of more than 50 policies to expand research, development, and innovation for drugs, medical devices, and personal care products. During the COVID-19 response, Stephen worked to secure billions of dollars for research, development, distribution, and promotion of vaccines, treatment, and diagnostic tests in the CARES Act, the Fiscal Year 2021 Omnibus, and the American Rescue Plan Act.

Photo of Michelle Chipetine Michelle Chipetine

Michelle Chipetine is a counsel in Crowell & Moring’s New York office and a member of the firm’s Intellectual Property and Health Care groups. Michelle’s practice focuses on patent litigation and representing health care entities and not-for-profit corporations on a wide range of…

Michelle Chipetine is a counsel in Crowell & Moring’s New York office and a member of the firm’s Intellectual Property and Health Care groups. Michelle’s practice focuses on patent litigation and representing health care entities and not-for-profit corporations on a wide range of transactional, corporate, and regulatory matters. Michelle also maintains an active pro bono practice.

Michelle graduated cum laude from Fordham University School of Law, where she was a legal writing and torts teaching assistant and actively involved with Fordham’s Neuroscience and Law Center. During law school, Michelle worked for Mount Sinai Innovation Partners, where she facilitated the transfer and commercialization of technologies developed by Mount Sinai researchers. Michelle also studied neuroscience at Vassar College, where she graduated cum laude.