The United States Food and Drug Administration (FDA) released a new draft guidance that provides information for medical product manufacturers, packers, and distributors, on how FDA evaluates firms’ medical product communications – including promotional materials – that present information not contained in the FDA-required labeling for the product, but that is consistent with such required labeling.
Various medical product firms have told the FDA that they would like to communicate data and information about the approved/cleared uses of their products, including information not contained in their products’ FDA-required labeling. As a result, the FDA issued this draft guidance for all drugs and devices, including those that are licensed as biological products, and animal drugs.
Because a communication that is consistent with a product’s FDA-required labeling could nonetheless misbrand the product and subject a firm to enforcement action if the representations or suggestions made in the communication are false or misleading, this guidance also provides general recommendations for conveying information that is consistent with the FDA-required labeling in a truthful and non-misleading way, as well as examples to illustrate these concepts. Interestingly, missing from the guidance document is any mention of off-label communications.
If a firm’s communication is consistent with the FDA-required labeling, that communication alone is not viewed by FDA as providing evidence of a new intended use. Further, FDA does not view a communication that is consistent with the FDA-required labeling as failing to comply with the Federal Food, Drug, and Cosmetic Act’s (FD&C Act) requirement that a medical product’s labeling bear adequate directions for use, based solely on the fact that it presents data and information that are not reflected in the product’s FDA-required labeling.
Examples of Information that Could Be Consistent with FDA-Required Labeling
The following examples are listed as some of the examples the FDA provides of information that could be consistent with the FDA-required labeling.
- Information based on a comparison of the safety or efficacy of a medical product for its approved/cleared indication to another medical product approved/cleared for the same indication (e.g., a firm’s communication provides information from a head-to-head study indicating that its drug that is approved to treat high blood pressure in adults has superior efficacy to another drug that is also approved to treat high blood pressure in adults);
- Information that provides additional context about the adverse reactions associated with the approved/cleared uses of the product reflected in the product’s FDA-required labeling (e.g., the FDA-required labeling for a product identifies nausea as a potential adverse reaction and further indicates the product can be taken with or without food. A firm’s communication about the product provides information about how taking a product with food might reduce nausea);
- Information about the long-term safety and/or efficacy of products that are approved/cleared for chronic use (e.g., a firm provides post-marketing information for its product, which was approved/cleared for chronic use based on 24-week study data, regarding persistent safety and/or efficacy over 18 months);
- Information concerning the effects of a product that comes directly from the patient (i.e., patient-reported outcomes) when the product is used for its FDA-approved/cleared indication in its approved/cleared patient population (e.g., a firm’s communication provides information concerning patient compliance/adherence, or a firm’s communication provides information about patients’ perceptions of the product’s effect on their basic activities of daily living); and
- Information that provides additional context about the mechanism of action described in the FDA-required labeling (e.g., the FDA-required labeling for a drug product indicates it exerts its effects by binding to a certain receptor, and a firm’s communication provides additional information about the product’s selectivity for that receptor).
Examples that Are Not Consistent with FDA-Required Labeling
The FDA also included some general types of information that they do not consider to be consistent with FDA-required labeling, some of which are below.
- Information about the use of a product to treat or diagnose a different disease or condition than the product is approved/cleared to treat or diagnose (e.g., a product is approved/cleared to treat cardiovascular disease, and a firm’s communication provides information about using the product to treat diabetes);
- Information about the use of a product to treat a different stage, severity, or manifestation of a disease than the product is approved/cleared to treat (e.g., a product is approved/cleared only to treat severe asthma, and a firm’s communication provides information about using the product to treat patients with mild asthma);
- Information about using a product through a different route of administration or in a different tissue type than the product is approved/cleared for (e.g., a product is approved only for intramuscular injection, and a firm’s communication indicates the product can be injected intravenously); and
- Information about the use of a product in a different dosage form than what is set forth in the FDA-required labeling (e.g., the product’s approved dosage form is a capsule, and a firm’s communication provides information about use of the product as an oral solution).
FDA Consideration Recommendations
The way a firm presents information that is consistent with the FDA-required labeling (including the express and implied claims made and the overall impression created by the communication as a whole) affects how the information is understood. The following are some high-level recommendations for firms to consider when developing their presentations of information that is consistent with the FDA-required labeling to help ensure the presentations do not mislead the applicable audience(s):
- Any study results or other data and information that are relied upon to support a firm’s communication should be accurately represented in the communications. Moreover, material aspects of study design and methodology for any studies relied on should be clearly and prominently disclosed in firms’ communications to allow audiences to accurately interpret the information (e.g., type of study, study objectives, product dosage/use regimens, controls used, patient population studied), and material limitations related to the study design, methodology, and results should also be disclosed in a clear and prominent manner.
- The communication should accurately characterize and contextualize the relevant information about the product, including by disclosing unfavorable or inconsistent findings. For example, if a firm presents efficacy results from a post-marketing study of its product that evaluated the effect of the product on two different endpoints, such as overall survival and progression-free survival, and the product failed to demonstrate an effect on one of these two endpoints, the firm should disclose this in the communication, rather than selectively presenting only the positive efficacy results.
- For communications that present data or information that is not in the FDA-required labeling, but where the FDA-required labeling contains other data or information related to what is being represented/suggested in the communication, the communication should also include the data or information from the FDA-required labeling to provide the audience with appropriate context. For example, if a communication provides post-marketing information about the types and rates of occurrence of adverse events that have been observed in practice, the communication should also include information from the FDA-required labeling about the types and rates of occurrence of adverse reactions observed in clinical trials to provide context.
The guidance document also provides several examples for applicable audiences to review, and to determine if their situation is similar. The examples also provide a bit of extra insight into FDA’s thought process and goal with the guidance document. In general, guidance documents do not establish legally enforceable responsibilities. Instead, they describe the Agency’s current thinking on a topic and should be looked at only as recommendations, unless there are specific regulatory or statutory requirements cited.