Recently, the U.S. Food and Drug Administration (FDA) issued a statement and proposed rule clarifying the types of evidence that the FDA considers when determining the "intended use" of a product. Intended use is important because it determines whether, and how, a product is regulated by the agency.
There are several ways in which product manufacturers can run afoul of the FDA (and other agencies like the Federal Trade Commission (FTC), and the Department of Justice (DOJ)), when promoting and advertising products beyond their approval or clearance. Examples include:
1) Dietary supplement manufacturers who make drug claims—for example, "Vitamin C cures COVID-19."
2) Cosmetics manufacturers who attempt to sell product as a cosmeceutical (e.g., a product that claiming both a cosmetic and a pharmaceutical benefit).
3) Drug manufacturers who promote off-label in a way that is false or misleadingâ€”for example, "our drug, which is approved to increase ocular moisture, also is good for treating age related macular degeneration (AMD)," when there is no evidence that the drug may be effective as a treatment for AMD.
Advertising and promotional claims that go beyond an approved or cleared intended use can result in a product being misbranded. Misbranded products subject to FDA-issued Warning Letters will require corrective action by the product manufacturer.
Further, should promotional claims result in a Warning Letter, in addition to being required to take corrective action, competitors will often attempt to use the Warning Letter to gain marketplace advantage. Finally, off-label promotion may result in a company, or officers thereof, being criminally prosecuted. Therefore, product manufacturers should carefully consider the proposed rule's explanation of the types of evidence the agency will use to determine intended use.
The Proposed Rule
The proposed rule follows on the heels of earlier attempts, transpiring over several years, to arrive at a final rule. Why has this become a multi-year process? In part, the answer is because intended use and evidence of intended use, at times, is not clear-cut; and in part because product manufacturers have commercial free speech rights under the First Amendment. The proposed rule lists evidence the FDA will consider in determining intended use, as well as evidence the FDA will not employ by itself when the agency makes a determination of intended use.
Express Claims and Representations
These include "labeling claims and representations," as well as "advertising matter, and oral or written statements by persons responsible for the labeling, or their representatives." An example of an express claim includes "to be administered twice daily for the treatment of Gram-positive bacterial infections."
The proposed rule defines an implied claim as any "claim or statement made by or on behalf of a firm that implicitly represents a product for a particular use." Suggestive names can give rise to implied claims. For example, the proposed rule exemplifies the name Shroomz (presumably implying that Shroomz produces the same effects as psilocybin, a component of magic mushrooms, that is converted in the body to psilocin which has psychoactive properties).
Statements of use, such as "[f]or best results use approximately 30-45 minutes prior to engaging in sexual intercourse," are also cited as potentially conveying implied claims. That directions or partial directions for use may convey intended use exemplifies the lack of clarity that can arise when the agency determines intended use under an implied claim. If the above statement of use is on a breath freshener, what does that imply about intended use? What if the above statement is found on a dietary supplement containing co-enzyme Q10? What about on a dietary supplement labeled for helping to maintain a healthy reproductive system or cardiovascular system?
Product Characteristics and Design
Here, the proposed rule, as an example, cites to products containing 2,4-dinitrophenol (DNP). DNP was used in the early part of the last century for weight loss. DNP was effective because it inhibited adenosine triphosphate (ATP) production in mitochondria. While DNP was effective for weight loss, it unfortunately also led to more than 60 deaths because of associated toxicities including hyperthermia, tachycardia, diaphoresis, and tachypnoea. Thus, the proposed rule cites to inclusion in a product of any substance as a product characteristic where the substance has "known physiological effects" and is "unapproved for any medical use."
The proposed rule also cites to product designs or features. An example in this evidence class includes "a stent that is specifically sized for a use that is different from the purported use" and "a device that includes software with a diagnostic function when the purported use does not include diagnosis." Taking the last example, in a scenario where a manufacturer included a diagnostic function in the software, but kept the function locked and intended the lock to remain until the manufacturer could obtain 510(K) clearance for the diagnostic function software, is this evidence of an intended use?
Circumstances of the Sale or Distribution
This includes to whom and for whom the products are offered. Examples include, for a drug, a firm's "repeated proactive detailing and delivery of large amounts of product samples to a health care provider whose patient population does not fall within the product's approved population."
The proposed rule also includes safe harbors that, standing alone, are not determinative of intended use. For example, the proposed rule states that "a firm will not be regarded as selling an unapproved product based solely on that firm's knowledge that the product is being prescribed or used by health care providers for such use." Specifically, the proposed rule exemplifies a scenario where:
A pharmaceutical firm tracks sales and distribution metrics. The firm notes that one of its products, approved for use only in adults, is being ordered by and distributed to many medical practices that treat exclusively pediatric populations. The firm does not give any direction to its sales or marketing staff to disseminate samples or information about this product to these pediatric practices.
Also, the proposed rule recites that "knowledge in combination with conduct that falls within a safe harbor would not be determinative of intended use." For example:
A pharmaceutical firm tracks sales and distribution metrics. The firm notes that one of its products, approved for the treatment of adult patients with acute lymphoblastic leukemia (ALL), is being ordered by and distributed to many medical practices that treat exclusively pediatric oncology populations. The firm also notes that the National Comprehensive Cancer Network clinical practice guidelines (CPG) for the treatment of ALL in pediatric patients recommends the firm's drug product as a treatment option. The pharmaceutical firm distributes copies of the CPG at medical conferences, following all recommendations made in the revised draft guidance, "Distributing Scientific and Medical Publications on Unapproved New Uses—Recommended Practices". The firm does not give any direction to its sales or marketing staff to disseminate samples or information about this product to practices that treat pediatric cancer patients exclusively.
Other examples that, standing alone, are not determinative of intended use include:
During an internal meeting, a firm's CEO displays a slide of internal sales projections for its approved product. The slide reflects potential sales for an unapproved use that is widely recognized as the standard of care; and
Following a clinical trial, the sponsoring firm prepares a plain-language summary of the aggregated clinical trial results and provides the summary solely to clinical trial participants to acknowledge their contributions to scientific and medical advancement (not to inform prescribing and use decisions). The summary provides a factual, balanced, and complete presentation of the trial results, including relevant safety information and any limitations of the study. The summary does not make any conclusions about the safety or effectiveness of the unapproved product or the unapproved use, and it includes a conspicuous and prominent statement that the product or use has not been approved, cleared, or licensed by FDA; and
The firm's official social media account "follows" the social media account for a 501(c)(3) non-profit that supports patients with a rare disease for which there is no FDA-approved treatment. The firm is in the process of investigating one of its FDA-approved products for use in the rare disease that the non-profit account supports. The non-profit account disseminates messages about charity events, scientific conferences, support groups, and rare disease research and drug development. The firm account does not make any comments or otherwise endorse any specific posts on the non-profit account. (Emphasis added.)
The agency's determination of intended use, and what constitutes evidence of intended use, does not always follow bright-line rules. And companies in certain circumstances enjoy First Amendment commercial free speech protections. Marketing regulated products while navigating these legal waters can be tricky, and companies are encouraged to involve counsel early and regularly.