Revision 2 of the FDA Guidance for Industry “Communications From Firms to Health Care Providers Regarding Scientific Information on Unapproved Uses of Approved/Cleared Medical Products: Questions and Answers” was published on January 6, 2025 and it finalizes the previous draft version. This is a procedural guidance that applies to medical products regulated by CDER, CBER, CDRH, CVM, or OC. As the guidance states on page 8, health care providers (HCPs) “generally prescribe and use approved/cleared medical products for unapproved uses when they judge that the unapproved use is appropriate for their particular patient – whose characteristics and needs may differ from the characteristics of the population(s) reflected in the approved use(s).” This scenario is most common for patients with diseases for which there is no treatment or when the health care provider has exhausted all medical products with approved uses for the disease. HCPs are likely to be interested in communications regarding scientific information on unapproved use(s) of approved/cleared medical product (hereafter referred to as SIUU communications), whether supportive or providing information on harm that could result from use of the product so that they can make the best decision for their patient(s). This new guidance outlines the type of SIUU communications that a firm can share with HCPs so the best decisions related to patient care can be made while not compromising the process for obtaining an approved indication.
This guidance outlines how to ensure that an equal balance of the newest information is available to HCPs while also communicating that the use/treatment is not an approved indication that has been investigated formally and/or evaluated by the FDA. Some primary takeaways from the guidance:
- “A key tenet underlying this enforcement approach is that, to promote the public health, any individual firm-initiated communication of scientific information about unapproved use(s) of that firm’s approved/cleared medical product(s) should be truthful and non-misleading and should provide and appropriately present all information necessary for HCPs to understand and evaluate the strengths and weaknesses, validity, and clinical utility of the scientific information on unapproved use(s) in that specific communication.”
- The guidance provides recommendations on how SIUU communications can be initiated and the types of source publications that are considered acceptable, including published scientific or medical peer-reviewed journal articles, published clinical reference resources, or firm-generated presentations.
- The guidance also describes how to present information and include all of the sources of the information, including when SIUU communications should be removed.
Some key information is provided in Section V, Question and Answers. This section discusses that source publications may be appropriate only if they have studies and analyses that are scientifically sound; specific examples are provided for human and animal drug study criteria and device studies. A key message is also to make sure that current studies are provided and, if an older study is being relied upon, that the results have not been contradicted by a new study. Any SIUU communications should be presented in a way that is unbiased and does not interfere with HCP understanding and evaluation of the scientific information, including its limitations. If the publication does not include the details of the study design, this information should be provided. If the SIUU is a firm-generated presentation, the firm must be very careful to cite the source(s) for the information (and the source(s) should be provided) and be truthful and non-misleading. The materials should not encourage the unapproved use of the medical product and the firm must provide disclosures (in addition to the other items mentioned under Q5). This concern for firm-generated presentations is because such materials have a greater chance for bias as there is no third-party review.
The FDA also recommends that there is a statement regarding the unapproved use(s) of a medical product and limitations, restrictions, cautions, warnings, or precautions that are present in the FDA-required labeling about the unapproved use(s). The currently approved labeling should be included, and any serious, life-threatening, or fatal risks that are detailed in the approved labeling or known by the firm and that are relevant to the unapproved use(s) should be specifically stated. The exception to this requirement is when a Clinical Practice Guidelines (CPG) is published (which is a general communication that references a range of medicinal products and the discussion does not primarily focus on one or more of a firm’s medical products); in such situations, a more general statement regarding safety and effectiveness for unapproved use(s) can be included rather than reference labeling for specific products (wording examples are provided in the guidance).
There should also be a disclaimer regarding any relationships between the firm and the author(s) of the publication(s). Any disclosures should be clear and presented prominently in each of the media types; that is, if there are both audio and visual components, disclosures must be presented in each.
SIUU communications should not provide/include any promotional materials as this could lead to a misunderstanding that the SIUU communication is related to an approved indication. Additionally, SIUU information should only be presented in platforms that allow all of the necessary disclaimers and disclosures to be included; therefore, if a platform has character limitations that would not allow for representation of all of the information mentioned in this guidance, it would not be an appropriate platform for dissemination of the SIUU.
Regardless of whether the SIUU communication is a publication, CPG, firm-provided presentation, or any other type of documentation, the communication should be provided in an unabridged format and, wherever possible, should include the entire text. If the entire text is not provided, the firm must ensure that all necessary information is provided to allow HCPs to make conclusions regarding the care of their particular patient(s) based on the potential risks involved.
Though it isn’t often that Industry is encouraged to communicate regarding unapproved uses of a medical product, this guidance provides a fair balance of expectations when it could contribute to patient treatment. If you need assistance reviewing your SIUU communications to ensure compliance with this guidance, please contact Lachman Consultant Services, Inc. at LCS@LachmanConsultants.com and we can guide you through the process.