Off-Label Promotion and Product Liability Considerations

The FDA has suffered a few litigation setbacks relating to off-label promotion oversight. In these cases, the government's attempt to take enforcement action against dissemination of off-label information was blocked as violating the U.S. Constitution's First Amendment guarantee of the right to freedom of speech.

To briefly recap the litigation history, Amarin Corp. successfully defended its ability to disseminate, proactively, information that its FDA-approved Vascepa® (icosapent ethyl) capsules could provide certain potential cardiovascular benefits not in the approved label. The U.S. district court in New York found that Amarin could distribute off-label information, so long as it was “truthful and not misleading,” without fear of FDA enforcement. Because Amarin's actions involved accurate and substantiated information about off-label uses, the court said the FDA should leave Amarin alone. Rather than continue the litigation after Amarin won a preliminary injunction in August 2015 against FDA enforcement, the government decided to settle with the company.

The Amarin settlement did not resolve a number of issues, however. For example, without clear guidance from the FDA, it remains unclear what is meant by the phrase, “truthful and not misleading,” and who ultimately makes that decision. Furthermore, it is not clear what type of (and how much) scientific substantiation will be required to support an off-label claim. In addition, while the Amarin settlement focused on off-label information to the medical community, it is not clear whether the FDA might take a more protective, paternalistic approach toward off-label promotion directed to consumers.

Notwithstanding the uncertainty surrounding FDA enforcement in the off-label promotional area, the agency is not sitting idly. Specifically, the FDA's Office of Prescription Drug Promotion (OPDP) sent Untitled Letters to two prescription drug manufacturers for direct-to-consumer television advertisements that it alleged made “false or misleading misrepresentations” about the products' safety and risks. See http://bit.ly/2j90NRr; http://bit.ly/2j8VC3I. The third letter, a Warning Letter, went to a company for a website that also misrepresented the product's safety and did not provide the drug's full indication. See http://bit.ly/2iA4y1b.

What the Letters Contained

All three letters focused on the presentation of risk information. While we will not discuss each letter in detail, as they are fact-specific, we will identify OPDP's major objections and note our observations.

In one television advertisement, the company provided risk information but, in OPDP's opinion:

Those compelling and attention-grabbing visuals and SUPERs, all of which are unrelated to the risk message, in addition to the frequent scene changes and the other competing modalities such as the musical interjections, compete for the consumers' attention. As a result, it is difficult for consumers to adequately process and comprehend the risk information. The overall effect undermines the communication of the important risk information and thereby misleadingly minimizes the risk associated with the use of [the product]. The presentation in the video is especially problematic from a public health perspective given the serious risks associated with the drug.

Concerning another television advertisement, issued the same day as the one OPDP complained of above, the agency used similar and, at times, verbatim language to express concern:

In the Warning Letter, issued the day after the Untitled Letters, OPDP said that the company's webpage promoted the product's benefits but failed to communicate “any” (emphasized by the agency) risk information. In addition, OPDP found that there were superiority claims made about the product's safety, without supporting data and, in fact, the Prescribing Information included a Black Box Warning, a highlighted warning statement, and identified other safety issues.

Separate from FDA's enforcement letters, the Pharmaceutical Research and Manufacturers of America (PhRMA) and the Biotechnology Innovation Organization (BIO), two of the leading pharmaceutical trade associations, issued a document, “Principles on Responsible Sharing of Truthful and Non-Misleading Information about Medicines with Health Care Professionals and Payers,” discussing off-label information. The document discusses how companies may disseminate “truthful and not misleading” information, even if the uses are not FDA-approved. The FDA has not endorsed these Principles, but there are many in industry who think this “truthful and not misleading” standard might become the new norm.

Recommendations to Minimize Risk

Many companies have become emboldened by the litigation, the FDA's hesitancy to take recent enforcement action in the off-label space, and the PhRMA's Bio Principles. However, caution is advised.

The FDA's enforcement letters are posted on its website. Injured parties and counsel can use these letters as examples of noncompliance with the law and, perhaps, causation. The FDA states that a company engaged in off-label or misleading information will be fodder for a judge and jury. And even if the agency does not decide to issue an enforcement letter, if someone is injured by a pharmaceutical product and a link can be made to an off-label use, promoted by the company, the negotiation discussions will likely turn to settlement, rather than a see-you-in-court response.

Companies cannot become complacent and have a false sense of security. The FDA's near-term enforcement inaction concerning off-label promotion will not protect them from exposure, particularly for direct-to-consumer advertising of off-label uses. Companies should utilize internal Promotional Review Committees to evaluate whether materials comply with FDA requirements, company procedures, and the “truthful, not misleading” standard (although this standard is not the law of the land). These committees, comprised of regulatory, medical, and legal personnel, can evaluate claims to maximize regulatory compliance and minimize liability risks.

Furthermore, companies must stay current on scientific developments, and train employees accordingly, to ensure that any off-label information disseminated remains truthful and not misleading.

***** Alan G. Minsk, a member of this newsletter's Board of Editors, is a partner and practice leader of Arnall, Golden, Gregory LLP's Food and Drug Practice. He focuses his practice on advising pharmaceutical, biologic, medical device, cosmetic and food companies, on all legal and regulatory matters relating to the FDA and DEA.