Basics

The FDA’s ability to engage in speaker- and content-based restrictions is limited by the First Amendment, which protects free speech, including commercial speech. While the FDA regulates medical product marketing to safeguard public safety by ensuring accurate communication about the safety and efficacy of these products and verifying the absence of false or misleading information in marketing messages, it must also carefully balance this regulatory authority with constitutional protections. As discussed next, courts have generally held that the FDA cannot impose blanket prohibitions on truthful, nonmisleading information about lawful uses of medical products. This limitation necessitates that depending on the communication, the FDA’s restrictions be narrowly tailored to serve a substantial government interest, such as protecting public health, without unduly infringing on free speech rights.

Overview of the Medical Product Communications That Are Consistent With the FDA Required Labeling—Questions and Answers (CFL) Guidance

While there have been previous FDA related guidance documents and discussions thereof, this matter begins with the 2018 FDA guidance on medical product communications that are consistent with FDA-required labeling, commonly called the FDA’s CFL guidance, which resulted from the FDA’s losses from the Sorrell v. IMS Health Supreme Court case, the Amarin and Caronia cases, multiple citizens petitions, and more. The guidance speaks to the Court’s concerns about speaker-based and content-based restrictions. The guidance further provides a framework for evaluating whether communications about approved products, which contain information not in the FDA-required labeling, are consistent with that labeling.

Generally speaking, the FDA uses three factors to determine whether the representations or suggestions in a product communication are consistent with the product’s FDA-required labeling.

1. How the information in the product communication compares to the information about those conditions of use in the FDA-required labeling.
   Considerations include:
   1. Indication – Are the representations/suggestions about a different indication than as approved by the FDA?
   2. Patient Population – Is the represented/suggested patient population different from the one in the FDA-approved labeling?
   3. Limitations and Directions for Handling/Use – Do the representations/suggestions in the communication conflict with the use limitations or directions for handling, preparing, and/or using the product reflected in the FDA-required labeling?
   4. Dosing or Use Regimen/Administration – Do the representations/suggestions about the product conflict with the recommended dosage or use regimen, route of administration, or strength(s) (if applicable) set forth in the FDA-required labeling?
2. Do the representations/suggestions about use of the product in the product communication increase the potential for harm to health relative to the information reflected in the FDA-required labeling?
3. Do the directions for use in the FDA-required labeling enable the product to be safely and effectively used under the conditions represented/suggested in the product communication?

Each factor identified above has multiple considerations. However, the guidance outlines key factors and recommendations to ensure that such communications are truthful, nonmisleading, and provide adequate directions for safe and effective use. There are key takeaways:

1. Companies are still wrestling with understanding this guidance, and it is not uniformly implemented across the field. Much of this reticence to engage in CFL communications can be attributed to the chilling effect of high penalties imposed not just by the FDA, but also the Centers for Medicare & Medicaid Services (CMS), US Department of Health and Human Services, Office of Inspector General (OIG), and the United States Department of Justice (DOJ). Noncompliance has already resulted in multiple billions in penalties in the past. Nevertheless, companies are taking active steps to create a compliance program around this guidance, but execution has been limited at best.
2. This guidance has not been extensively cited by lawyers to justify promotional compliance concerns. This is expected to change since this goes to the heart of the issue: the FDA knows that doctors can talk to each other. However, it specifically prevents pharma companies from speaking to doctors about certain off-label concerns. This raises concerns of speaker- and content-based restrictions, two critical negative aspects in the court’s eyes.
3. In the end, this is just a guidance and is by definition not legally binding upon the FDA and industry. Lawyers have begun to challenge administrative agencies such as the FDA by asserting that such behavior has the chilling effect of regulations without appropriate oversight and hearings. So expect more from the Supreme Court as early as the present term.

It is also important to recognize that despite concerns about the FDA’s alleged jurisdiction over truthful and nonmisleading communications, companies do not have carte blanche over communications. In the recent US v. Facteau appellate decision, the 1^st Circuit reviewed the record and determined that the medical device company corporate executives had taken significant steps to promote the product only for an off-label use as opposed to the “intended use” stated in its section 510(k) submission. This was based on internal corporate documents, regulatory history, sales rep training and experience, and surgeon training. The court determined, after a 30-day jury trial, that the jury reasonably found two former executives of a medical device manufacturer guilty of multiple misdemeanor violations of the Federal Food, Drug, and Cosmetic Act (“FDCA”) for commercially distributing an adulterated and misbranded medical device.

Overview of the Drug and Device Manufacturer Communications With Payers, Formulary Committees, and Similar Entities (FDAMA 114 Guidance)

The FDA’s “Drug and Device Manufacturer Communications With Payors, Formulary Committees, and Similar Entities” guidance was also proposed in June 2018 and expires on September 1, 2024. It addresses the communication of healthcare economic information (HCEI) by pharmaceutical and medical device manufacturers to payers. This guidance provides clarity on how manufacturers can share HCEI regarding both approved and unapproved products, as well as unapproved uses of approved products. The primary objective is to ensure that communications are truthful, nonmisleading, and based on competent and reliable scientific evidence (CARSE).

This guidance again raises First Amendment concerns. In 1999, in the Greater New Orleans Broadcasting Assn., Inc. v. United States, the court held that they were unable to constitutionally distinguish between providing the identical information, with identical disclaimers and limitations, to one “sophisticated” audience while prohibiting that information’s distribution to another “sophisticated” audience. This is consistent with the idea that the same doctor can hear the same information as a member of the formulary, but not be able to hear it as a sophisticated prescriber taking care of an individual patient. This raises questions of content-based restrictions.

Overview of the Pre-approval Information Exchange (PIE) Act

The prescription drug and medical device Pre-Approval Information Exchange Act, also known as the PIE Act, was passed as part of Congress’s December 2022 omnibus spending bill and was enacted to bridge a significant communication gap between drug developers and healthcare payers. Before the PIE Act, there were strict limitations on what information could be shared about investigational drugs before they received FDA approval. This delayed when the information could be shared which subsequently caused payers to take time determining whether new products will be covered and/or on formulary. The PIE Act addresses these inefficiencies in healthcare planning and patient access to new treatments.

The PIE Act allows for the exchange of critical information about investigational drugs with payers and formulary committees, enabling them to prepare for the introduction of new therapies. This pre-approval communication includes data on the clinical trial phases, economic implications, and anticipated approval timelines.

Overview of the Communications From Firms to Healthcare Providers Regarding Scientific Information on Unapproved Uses of Approved/Cleared Medical Products (SIUU) Guidance

In 2023, the FDA put forth the recent guidance titled Communications From Firms to Health Care Providers Regarding Scientific Information on Unapproved Uses of Approved/Cleared Medical Products. Commonly called the SIUU guidance, this is a continuation of the FDA’s 2009 and 2014 guidances and 2016 public hearing. This guidance was analyzed in an article published by the DIA Global Forum in January of 2024. It focuses on the communication of scientific information about unapproved uses of approved medical products. It’s designed to ensure that healthcare providers have access to the latest scientific data to make informed decisions, even if the information pertains to uses not included in the FDA-approved labeling.

The SIUU guidance permits the dissemination of scientifically rigorous information that can help healthcare providers understand potential benefits and risks of unapproved uses, thereby enhancing patient care and safety.

Unlike the CFL guidance which is intended for a broader regulatory audience, the SIUU guidance addresses communications between “Firms to Health Care Providers.” It also limits the conversations to “unapproved use(s) of approved/cleared medical products.” This could be relevant “to inform clinical practice decisions for the care of an individual patient.” However, Firms (aka the pharmaceutical or medical device companies) should generally be careful because companies should not engage in the unauthorized practice of medicine. Such conversations about unapproved uses of approved/cleared medical products to guide clinical practice decisions, if inappropriately done, may fall outside the scope of the FDA’s jurisdiction and also exceed the scope of medical affairs and the 2011 FDA guidance on Responding to Unsolicited Requests for Off-Label Information.

Implications for Medical Affairs and HEOR Programs

What do these guidances mean for medical affairs and Health Economics and Outcomes Research (HEOR) programs? For medical affairs teams, it means developing robust strategies for communicating scientific data in a compliant manner. It’s crucial to ensure that all shared information is accurate, comprehensive, and nonmisleading. For HEOR programs, the focus should be on ensuring that research methodologies are robust and findings are communicated clearly.

On the other hand, in light of the various court decisions discussed above, these guidances raise significant questions on the FDA’s ability to regulate off-label speech based on speaker- or content-based restrictions.

Conclusion: Importance of Legal Guidance

Navigating these complex regulations is necessarily daunting and can exceed typical regulatory considerations since they must be contextualized based on not only guidance documents, but also on laws and court opinions to ensure public safety and accurate information about novel medical products. The table below describes some of the key differences between the primary list of guidance documents discussed above and the PIE Act.