How prescription drugs are used is a critical part of obtaining their benefits safely, so the law requires thorough disclosure of any consequences of using the drug. Promotional materials should accurately communicate the drug's indications and benefits, and communicate the most important risks in a manner reasonably comparable to the presentation of benefits.

For most prescription drugs, promotional materials do not need to be submitted to FDA before use. Rather, they are submitted at the time of their initial use. FDA's review of promotional materials therefore generally occurs after the materials have already appeared in public, and any action FDA takes will also occur after the materials have been seen publicly.

Untitled letters are used for less severe violations of the Federal Food, Drug, and Cosmetic Act and regulations. Violations that might receive an untitled letter include overstating the effectiveness of the advertised product, suggesting a broader range of conditions than those for which the drug was approved, or misleading through inadequate context or lack of balancing information.

Warning letters address more severe violations, including those creating serious safety or health risks, and those involving egregious or repetitive conduct, which, if not promptly and adequately corrected, could lead to further enforcement action. Complete omission of any safety information from the body of a promotional piece is a common basis for a warning letter.

The most common violation we see is omitting or minimizing risk information, an obvious concern since communicating risks to the public is so important. Healthcare providers must weigh the risks and the benefits of drugs in deciding whether to prescribe them. And consumers need to understand the benefits and risks of drugs so they can have informed discussions with their healthcare providers. The American public, whether healthcare provider or consumer, is entitled to a balanced picture of the drug when it is promoted.

Other violative promotion includes claims that a drug is better or more effective than is stated in the approved product labeling (especially for products with relatively low efficacy), safer than demonstrated (fewer side effects, lower severity or incidence), or better or safer than other products, without substantial supporting evidence. Generally, FDA requires two adequate and well-controlled head-to-head studies.

We also see violative promotional materials that contain incomplete communication of the indication, misleading presentation of data or risk-benefit information (e.g., selective presentation of only favorable data, suggesting clinical significance where there is none, or cramming all the risk information onto the bottom of the page in very small type). Another common violation in promotional material: broadening an indication or suggesting unapproved uses. Television broadcast ads present distractions in the audio or visual portions of the ad that divert attention from the risk information.

DDMAC posts untitled letters and warning letters on the FDA/CDER Web site. This provides information to all regulated parties regarding our enforcement activities and rationale. And, we hope, it helps teach regulated parties to avoid violations cited in the letters. Reviewing our untitled letters and warning letters reveals the types of violations that we see on a regular basis.

Companies must submit the promotional material to FDA (along with form FDA-2253) at time of first use as required by the regulations. Promotional materials include sales aids, Web sites, brochures, exhibit booth panels, reprint carriers, posters, booklets, mailing pieces, bulletins, catalogs, letters, videos, and slides, as well as advertisements in published journals, magazines, periodicals, or newspapers, and advertisements broadcast on radio, television, or telephone. Failure to submit is another common violation, and it can often exacerbate other violations in the promotional material by allowing them to continue for a longer period of time.

We also provide guidance that is posted on the FDA/CDER Web site, and additional information is available on the DDMAC Web site.

Lesley R. Frank, PhD, is senior advisor regulatory counsel within the Division of Drug Marketing, Advertising, and Communications (DDMAC) in the Center for Drug Evaluation and Research (CDER) at FDA. She can be reached at frankl@cderfda.gov