In the last year, the U.S. Food and Drug Administration’s (FDA’s) Division of Drug Marketing,
Advertising, and Communications (DDMAC) has issued a number of Warning Letters and
notices of violation addressing the presentation of risk information in marketing materials.
These enforcement actions are consistent with DDMAC’s May 2009 publication of Guidance
for Industry: Presenting Risk Information in Prescription Drug and Medical Device
Promotion, in which the FDA articulated a “net impression” standard for risk information
and discussed the requirement that risk information not be relegated to the end of
DDMAC’s persistent enforcement is beginning to affect the standards for the presentation of risk
information by requiring that risk information be presented throughout a piece. These new
standards raise complex questions about how to meet the evolving standards. Companies should
evaluate their current practices, educate brand teams and promotional reviewers on the new
standards, and adjust promotional practices to meet the FDA’s revised standards.
This Update summarizes trends in recent DDMAC enforcement by specific category of promotional
materials and provides a snapshot of selected letters. As shown below, the recent letters have
- References to the availability of risk information are insufficient. Merely linking to a Web
page or including a statement to see risk information located elsewhere does not meet the
requirement that risks be included.
- Risk information must be presented at the same time or in the same place as
effectiveness claims. It cannot be relegated to the end of a presentation or advertisement.
- All relevant risk information must be presented. Merely presenting a Boxed Warning or
highlighting common adverse reactions is insufficient. Effectiveness claims that are
presented must have all risk information relevant to those claims alongside them.
- Risk information must be displayed with a “prominence and readability reasonably
comparable” to claims presented in a promotional piece.
- Risk information must be as clear to the recipient of the promotional material as efficacy
claims. Risk information directed at consumers cannot be presented in complex medical
Journal Advertisements and Brochures — Turning the Page may be Problematic
Relevant risk information must be prominently displayed on the first page of a piece and reasonably
comparable to the presentation of efficacy claims.
- On January 22, 2010, Novalar Pharmaceuticals Inc. received a Warning Letter for
OraVerse. “The patient brochure prominently presents efficacy claims in large bolded font
size and colorful text and graphics surrounded by a significant amount of white space. In
contrast, risk information is presented in small black font, and in single-spaced paragraph
format on the last fold of the brochure.” Additionally, the presentation of risk information
using complex medical terminology in this consumer-oriented brochure was unacceptable.
- On November 5, 2009, Shire Development Inc. received a Warning Letter for Fosrenol.
The letter indicated that merely providing a statement to see full Prescribing Information,
even when the brochure was written for patients who already had a prescription for the
drug, was insufficient. Having the Prescribing Information in a packet that accompanied
the brochure failed to cure the violation.
- On December 18, 2009, Cepahlon Inc. received an Untitled Letter for Treanda. “Extremely
limited” risk information presented on the back cover caused the drug to be misbranded.
- On May 14, 2009, DDMAC issued a Warning Letter to Dexcel Pharma Technologies Ltd.
for PerioChip. Including the Brief Summary on the second page of the advertisement was
insufficient to provide appropriate qualification for claims made on the first page.
- On January 22, 2009, Abbott Laboratories received an Untitled Letter for Depakote. A
flashcard with no risk information on the front side was insufficient. “The statement,
‘Please see … Important Safety Information including Boxed Warnings … on reverse side’
included in small type in the lower left-hand corner of the of the Flashcard [did] not
mitigate this misleading presentation.”
Internet Promotion — Is There A One-Click Rule?
Generally, DDMAC’s letters regarding Internet-based ads have indicated that merely having a link
to risk information is insufficient.
- Sponsored Links: In fourteen untitled letters issued on March 26, 2009, DDMAC
asserted that sponsored links may not rely on a link to the product’s Web site for
presentation of risk information.
- Banner Ads: On March 9, 2009, DDMAC issued an Untitled Letter to GlaxoSmithKline for
Treximet. “[T]he risk information automatically scrolls in a small slice of the banner. The
text in the risk section is small and is formatted in single-spaced block paragraphs, making it difficult to read, and the information scrolls at a predefined speed. This automatic
scrolling and the density of the risk information make the presentation almost impossible
to read and comprehend in the time allotted. Unlike the efficacy claims in the banners, the
risk information is presented without any signals or other attention-grabbing devices to
alert readers that this is important information about the drug.”
- Web sites: On January 7, 2010, DDMAC issued an untitled letter to Bracco Diagnostics,
Inc. for Isovue. The Web site presented general safety claims but failed to include
important risk information from the PI. Including instructions to download a full PI on the
lower left-hand corner of each webpage did not cure the deficiency.
Video Presentations — Risks Must be Presented In the Same Format as the Benefits
DDMAC has issued two Warning Letters dealing with video presentations: one for a webcast video
and one for a DVD video. These presentations misbranded the drugs because risk information was
not presented early in the video and was not presented in a form comparable to the other
information presented in the video.
- On July 14, 2009, Abbott Laboratories received a Warning Letter for a Kaletra video in
which Magic Johnson was interviewed for over 11 minutes. The failure to present anything
beyond cursory risk information during the interview portion of the video was insufficient
as was presenting risk information in a telescript at the end of the interview.
- On May 12, 2009, Johnson & Johnson received a Warning Letter for Ultram ER. The letter
indicated that a failure to present any risk information during the first six minutes of a
seven minute video was insufficient. Further, presenting risk information in a rapidly
scrolling telescript “lacks comparable prominence to the benefit claims contained in the
testimonial portion of the webcast” and failed to include certain contraindications.
Print Ads — the “Main Body” of an Ad Must Include Prominent Balance
DDMAC has issued three untitled letters indicating that the main body of a print ad must include
relevant risk information “with a prominence and readability reasonably comparable to the claims of
effectiveness in the ad.”
- On January 7, 2010, Eli Lilly and Company received an Untitled Letter for Cymbalta. Risk
information presented on the page adjacent to the main body of an advertisement was
insufficient, even with a statement in the main body to see the left page. The letter
highlighted that the risk information was placed in a single column on a page with
unrelated content which “appear[ed] unconnected to the main body of the Print Ad and
[was] not likely to draw readers’ attention.”
- On January 27, 2009, DDMAC issued an Untitled Letter to Indevus Pharmaceuticals Inc.
for Sanctura. “Throughout the Journal Ad, effectiveness claims are presented using large,
bolded, colorful text and graphics. In contrast, the risk information that is presented is
relegated to the bottom of the first page of the Journal Ad and is presented in a single block paragraph in small, black font following a statement of the indication for use, without
any signal to indicate to the reader that it is important risk information.”
- On December 16, 2008, Abbott Laboratories received an Untitled Letter for Humira. Risk
information “presented at the bottom of the page, in white text on a pink background in
extremely small font size, and in single-spaced paragraph format that makes the
information extremely difficult to read” was insufficient given the clarity of the efficacy
presentation, which “us[ed] a very large font size and purple type surrounded by a
significant amount of white space.”
Other Enforcement Actions
- Waiting Room Sign: On January 26, 2010, Meda Pharmaceuticals Inc. received an
Untitled Letter for Astelin. Risk information presented “at the bottom of the sign after the
indication for the drug in extremely small font size and in a single-spaced format that
[made] this information very difficult to read” was insufficient given claims “in large, colorful
font.” Inclusion of a bolded statement to “Please see accompanying full Prescribing
Information” did not cure the violation.
- Patient Profile Card: On November 6, 2009, Eisai Inc. received a Warning Letter for
Dacogen. Presenting risk information on the middle of the back cover of a 12-page card
was insufficient, especially given the risk information was “[i]n contrast to the large and
colorful effectiveness presentations contained in the first 11 pages.” A statement at the
bottom of each page to “Please see accompanying full prescribing information and
Important Safety Information” failed to cure the violation.
- Launch Display: On September 10, 2009, Allergan Inc. received an Untitled Letter for
Latisse. A small placard to the lower right of a visual timeline depicting the history of lash
enhancers was not sufficiently prominent, and its readability was not reasonably
comparable with the presentation of efficacy claims.