CHAPTER § 1.07 FDA's Requirements for Prescription Drug Advertising and Promotion

• Jurisdiction: United States

§ 1.07 FDA's Requirements for Prescription Drug Advertising and Promotion

[1] Introduction

Promotional materials are key to the success of marketing and selling a prescription drug. The promotion of a drug informs consumers of new and existing drugs, educates health care providers on how to use the drug, and differentiates the drug from competitor products. Additionally, promotional materials are among the most prominent ways in which pharmaceutical manufacturers communicate messages about products, goals, and company principles to their customers. The importance of promotional materials in the medical community, as well as their obvious visibility, make them among the most regulated forms of communication in the United States.⁵²²

Before 1962, the Federal Trade Commission ("FTC") regulated promotional activities for prescription drugs.⁵²³ When Congress enacted the 1962 amendments to the FDCA, it gave FDA authorization to regulate, among other things, the promotion of prescription drugs sold within interstate commerce.⁵²⁴

The term "promotion," however, is not defined by the FDCA or FDA regulations. Therefore, "promotional material" encompasses a broad category of written, printed, or graphic materials that includes drug "labeling" and "advertising."⁵²⁵ FDA regards all promotional material issued by a pharmaceutical company as either "labeling" or "advertising," allowing FDA's jurisdiction over promotional material to include virtually all product-specific materials issued by a company or its agent.⁵²⁶

[2] Definitions: Approved Product Labeling vs. Promotional Labeling and Advertising

As a starting point, understanding the distinction between "approved product labeling" for prescription drugs and prescription drug "promotional labeling" and "advertising" is critical to ensuring that promotional materials meet FDA regulatory requirements.

The term "label" is defined as a "display of written, printed, or graphic matter upon the immediate container of [the drug]."⁵²⁷ The term "labeling" is defined as "all labels and other written, printed, or graphic matter: (1) upon any article or any of its containers or wrappers, or (2) accompanying such article."⁵²⁸ The FDCA, as interpreted by the courts, defines "accompanies" broadly to include material textually explaining or supplementing a drug even though shipped separately from the drug.⁵²⁹ A drug label, therefore, could be a pamphlet distributed to consumers yet shipped completely separately from the drug itself.⁵³⁰ FDA regulations further define labeling as:

Brochures, booklets, mailing pieces, detailing pieces, file cards, bulletins, calendars, price lists, catalogs, house organs, letters, motion picture films, film strips, lantern slides, sound recordings, exhibits, literature, and reprints and similar pieces of printed, audio, or visual matter descriptive of a drug and references published (for example, the "Physicians' Desk Reference") for use by medical practitioners, pharmacists, or nurses, containing drug information supplied by the manufacturer, packer, or distributor of the drug and which are disseminated by or on behalf of its manufacturer, packer, or distributor. . . .⁵³¹

The above definitions encompass all materials that constitute "labeling." In practice, two distinct types of labeling emerge from those broad definitions: approved product labeling and promotional labeling.⁵³² It is important to understand the difference between the two, as regulation and enforcement of each is quite different.

[a] Approved Product Labeling

Approved product labeling refers to labeling that is approved by FDA as part of the premarket approval process for a prescription drug.⁵³³ This labeling is often described as the package insert or prescribing information ("PI").⁵³⁴ FDA-approved product labeling is the foundation upon which all promotional information about a drug is based. In other words, generally, promotional labeling and advertising may not contain information or claims not asserted in the FDA-approved product labeling.⁵³⁵ Notably, FDA has put forth guidance clarifying that promotional communications consistent with the FDA-required labeling ("CFL Guidance") are permitted as well.⁵³⁶ The CFL Guidance is discussed in more detail below.

[b] Promotional Labeling and Advertising

Promotional labeling includes all other materials fitting into the definition of "labeling" other than FDA-approved product labeling.⁵³⁷ The FDA regulation governing prescription drug advertisements also specifies categories of materials considered labeling under the Act⁵³⁸ and is commonly understood as a description of materials considered promotional labeling by FDA.⁵³⁹ Promotional labeling, although technically "labeling," is commonly regulated by FDA under the regulations that pertain to advertising activities.⁵⁴⁰

The term "advertising," like the term "promotion," is not defined by the FDCA. FDA regulations, however, provide some insight into the Agency's understanding and definition of the term, referring to "advertisements" in the following provision; "Advertisements subject to [FDA regulation] include advertisements in published journals, magazines, other periodicals, and newspapers, and advertisements broadcast through media such as radio, television, and telephone communication systems."⁵⁴¹ "Advertising," therefore, is seemingly not distinguished from "labeling" (especially "promotional labeling") based on content or subject matter, but rather, based on the mode of dissemination of the information.⁵⁴²

[c] Consistent with the Label Communications

FDA requires that all promotional communications include only information about the drug that is within the drug's FDA-approved label ("on-label") or consistent with the FDA-approved label ("CFL").

The approved labeling, also referred to as the package insert or the prescribing information, should be viewed as the roadmap for all promotional communications. FDA put forth guidance clarifying the communications it considers consistent with the FDA-required labeling ("CFL Guidance").⁵⁴³ The guidance describes how FDA intends to treat promotional communications that are not contained in FDA-required labeling but are nevertheless consistent with FDA-required labeling. Per the CFL Guidance, information that is consistent with the FDA-required labeling is limited to information about the approved uses of a product. Notably, such consistent information will not be considered evidence of a new intended use or failure to provide adequate directions for use.

The guidance is significant for two main reasons: (1) it confirms that not all manufacturer communications involving information outside the four corners of FDA-required labeling are considered "off-label"; and (2) it confirms that CFL communications need only be supported by "scientifically appropriate and statistically sound" evidence, a lower substantiation standard than previously required by the Agency.

The FDA created a three-factor test to determine whether communications for drug products are CFL. The three factors to be considered are as follows:

(1) How the information in the communication compares to the information in FDA-required labeling. With respect to this factor, FDA will consider information to be consistent with FDA-required labeling if: (A) representations or suggestions in the communication relate to the same indication as the one reflected in the product's FDA-required labeling; (B) the patient population represented or suggested in the communication is not outside the approved patient population reflected in FDA-required labeling; (C) the representations/suggestions in the communication do not conflict with the use limitations or directions for handling, preparing, and/or using the product reflected in FDA-required labeling; and (D) the representations/suggestions about the product do not conflict with the recommended dosage or use regimen, route of administration, or strength(s) (if applicable) set forth in FDA-required labeling.
(2) Whether the representations/suggestions in the communication increase the potential for harm to health relative to the information reflected in the FDA-required labeling.
(3) Whether the directions for use in FDA-required labeling enable the product to be safely and effectively used under the conditions represented/suggested in the communication.

The CFL Guidance includes several categories of communications that could be considered CFL. These include certain communications about comparisons, adverse reactions, onset of action, long-term safety or efficacy, patient subgroups, product effects, convenience, and mechanism of action. The guidance provides explanations and examples for communications about comparisons, product effects, and convenience. Specifically, the guidance lists the following types of potentially CFL communications:

(1) Comparisons—Information based on a comparison of the safety or efficacy of a medical product for its approved or cleared indication to another medical product's same approved or cleared indication.
(2) Adverse Reactions—Information that provides additional context about the adverse reactions associated with the approved or cleared uses of the product.
(3) Onset of Action—Information about the onset of action of the product for its approved or cleared indication and dosing or use regimen.
(4) Long-Term Safety/Efficacy Data—Information about the long-term safety and/or efficacy of products that are approved/cleared for chronic use.
(5) Specific Patient Subgroups—Information about the effects or use of a product in specific patient subgroups that are included in its approved/cleared patient population.
(6) Product Effects—Information concerning the effects of a product that may come directly from the patient (e.g., compliance/adherence, disease-related symptoms at interim timepoint, patient perceptions).
(7) Convenience—Information about a firm's drug that conveys that its administration time is more convenient than

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