On April 2, 2009, the U.S. Food and Drug Administration (FDA) publicly released fourteen “untitled” letters to major pharmaceutical firms challenging the use of “sponsored links” and alleging that the links make product claims but fail to provide required risk information. This is the latest example of the FDA addressing the regulatory standards for pharmaceutical Internet advertising in an ad hoc manner. For the last decade, the FDA has addressed important legal and policy issues surrounding the use of the Internet for pharmaceutical advertising in this way. Indeed, the FDA has affirmatively declined to articulate clear standards for online advertising, relying instead on its “print-based” media standards.
The development of interactive online media outlets offers pharmaceutical manufacturers new opportunities for professional and direct-to-consumer (DTC) advertising and promotion. Because the FDA has not provided guidelines for applying existing “print-based” rules to electronic media, online advertising poses challenges and risks for companies eager to embrace these new alternatives. In the absence of specific guidance from the FDA, pharmaceutical manufacturers must look carefully at FDA’s enforcement activity and at recent statements by agency personnel to effectively assess risks.
This Update reviews FDA’s enforcement activity aimed at online advertising and identifies those Internet applications that await FDA guidance.
Past FDA Statements and Actions on Internet Advertising and Promotion
FDA addresses online promotion on a case-by-case basis One early indication of FDA’s approach is a 2001 response to a Citizen Petition submitted by the Washington Legal Foundation (WLF).1 WLF’s petition requested that the FDA formally adopt a rule or policy that: (1) “information presented or available on a company’s Internet Web site, including hyperlinks to other third party sites, does not constitute ‘labeling,’” as defined by the Food, Drug, and Cosmetic Act (FDCA); and (2) “such information may, but does not necessarily, constitute advertising.”
The FDA did not agree with WLF, but rather took the position that “information about FDAregulated products that is disseminated over the Internet by, or on behalf of, a regulated company can meet the definition of labeling in section 201(m) of the Food Drug and Cosmetic Act.” The FDA also stated its position that “some product-specific promotion presented on non-company Web sites…would be viewed as advertising.” In sum, the FDA declined to offer Internet-specific standards for regulating online promotional material. Instead, the FDA concluded that it would proceed on a “case-by-case” basis in determining what online information would be subject to the labeling and advertising disclosure requirements.
The Distinction Between Advertising and Labeling
The FDCA defines “labeling” as any written, printed, or graphic matter on the immediate drug container, i.e., the label.2 Labeling also includes any information “accompanying” the drug.3 This provision has been interpreted broadly by the courts and the FDA to mean any material that is part of the “integrated distribution program” for a drug.4 Thus, “labeling” need not be limited to materials physically attached to the drug package, but extends to all materials that supplement or explain the drug product, including brochures, mailing pieces, catalogs, sound recordings, exhibits, reprints, and other printed, audio, or visual materials describing a drug.5
By contrast, the FDCA does not define “advertising.” FDA regulations list examples, including advertisements in journals, magazine, newspapers, and other periodicals, and broadcast media (e.g., radio, television, telephone).6 The FDA generally regards any material, other than labeling, as advertising if it promotes a drug product and is sponsored by or on behalf of a manufacturer. This distinction between advertising and labeling is critical because the categories trigger different regulatory standards. For example, advertising must include a “brief summary” of the drug’s side effects, contraindications, and effectiveness contained in the approved package insert (PI), while labeling must include adequate directions for use, i.e., the approved PI.
This general approach was recently restated by Nancy Ostrove, senior advisor to the Division of Drug Marketing, Advertising, and Communications (DDMAC), at a public meeting of the agency’s Risk Communication Advisory Committee in May 2008.7 According to Ms. Ostrove, DDMAC’s position is that manufacturers may choose whether to treat promotional material on the Internet as either labeling or advertising and should apply the applicable rules consistently. To our knowledge, most companies treat product Web pages as promotional labeling.
On April 2 the DDMAC made public 14 untitled letters to companies for violations related to sponsored links on search engines.8 The sponsored links result from searches for the brand names of either drug products or disease conditions on search engines such as Google and Yahoo. In virtually identical letters to each company, the DDMAC cited violations of the FDCA and labeling and advertising regulations for omission of risk information,9 inadequate communication of the indication,10 and failure to use required established names.11
The DDMAC asserted that the sponsored links misbrand the drugs because they include the name of the drug plus a claim and, therefore, must disclose risk and other information about the drug. The agency explained that providing the link to the product's Web site, where consumers could get more information about the drug’s risks and benefits, "does not mitigate the misleading omission of risk information." The letters also assert that the sponsored links failed to adequately communicate the drugs’ indication, or broadened the indication, by failing to disclose limitations to the indication for the drug, such as the appropriate patient population, disease stage, or use as a combination therapy. Finally, the sponsored links presented the brand names of the drugs and thus failed to use the required established names.
The DDMAC compared the sponsored links with reminder ads, which only include the drug name but do not include indications or other representations or suggestions about the drug12 and that are exempt from the requirement to present risk information. Several of the drugs addressed in the DDMAC letters carry boxed warnings on their approved labels and cannot be promoted through reminder ads under 21 C.F.R. sections 201.100(f) and 202.1(e)(2)(i). The letters leave companies limited options for online searches. Because adding the Important Safety Information (ISI) is likely impractical given current character limitations, search links for unbranded disease awareness pages may be the only alternative.
The Shire YouTube Warning Letter
In September 2008 the DDMAC sent a warning letter to Shire Development, Inc. (Shire) regarding its online marketing of Adderall XR, an ADHD treatment. FDA alleged that Adderall XR’s Web page and a video celebrity testimonial posted on YouTube on behalf of the company misbranded the drug in violation of FDCA sections 502(a) and (n) by overstating the drug’s efficacy, broadening its indication, and omitting important risk information. Additionally, FDA objected that the video testimonial had not been submitted to FDA as required by 21 C.F.R. 314.81(b)(3)(i).
This letter represents the first time that FDA has addressed material posted on YouTube in a warning letter. Though this distinction was noted in the pharmaceutical trade press,13 FDA did not emphasize that fact. The agency sent four other warning letters on the same day, all of which concerned false and misleading promotion of ADHD medication in traditional media. Only the Shire letter referred to YouTube, so it seems that the FDA focused on the drug class, rather than on the media used.
Search Engine Optimization and Metatags
Search engine optimization (SEO) is a marketing technique used to increase the likelihood that search engine users will be directed to a particular Web site. In its most common form, SEO involves the use of “keywords” metatags. Metatags are specific types of data in the HTML code used to create a Web site. Viewers of a Web page do not see the metatags, which store information about the page. Many search engines use the contents of the “keywords” metatag to index and rank Web pages in search results.
For some time, the FDA has alluded to metatags in its enforcement aimed at manufacturers’ Web sites.14 For example, the FDA reviewed Web sites of manufacturers of allegedly unapproved new drugs and alleged that Web site therapeutic claims indicate that the products are intended for the treatment of disease, and therefore drugs. The FDA also concluded that the products were not generally recognized as safe and effective for the described conditions, and thus new drugs. Additionally, the drugs were illegally marketed because they were not approved and were misbranded because the labeling did not give adequate directions for use.
Megatags supported two such allegations. First, 15 cyber letters sent in November 2005 included a paragraph describing the Federal Trade Commission’s laws governing unfair or deceptive advertising practices.15 This concluded with the sentence: “Be aware that product claims can be communicated to consumers in a variety of ways, including product name, web site name, product testimonials, endorsements, or use of metatags.” (emphasis added) Second, the FDA alleged that the therapeutic claims were “supplemented by the use of metatags [used] to bring consumers to your web site.” Numerous warning letters from 2008 follow this pattern.16 Examples of metatags noted by the FDA in these letters include basic terms such as “cancer,” “joint pain,” “alternative cancer treatment,” and “pancreatic cancer.” Thus, the FDA has been concerned that metatags may inappropriately drive Internet users to product Web sites and, additionally, broaden the indication of the drugs at issue.
Online Banner Ads for Black Box Products
In August 2008 the DDMAC sent an untitled letter objecting to eight online banner ads by Novartis Pharmaceuticals Corp. promoting Diovan, a “black box” product.17 The DDMAC warned that the banner ads presented efficacy claims but failed to communicate required risk information, thereby misbranding the drug.18 The DDMAC noted that the banner ads included links to the PI and Patient Product Information (PPI), but concluded that the presence of these links “does not mitigate the misleading omission of risk information from the banners.”
“One click” rule
The recent untitled letters call into question the “one click” rule, which many in industry believed that the FDA had embraced.19 In response to FDA’s request for comments on Consumer Directed Promotion in 2003, the FTC discussed the distinction between reminder ads/help-seeking ads and other ad formats, suggesting that the brief summary should be satisfied if the advertisement contains a link that leads directly to the main product Web page that includes the major statement of risks. The FDA held a public hearing on the same topic, but did not directly address the “one click” rule, and no draft guidance followed.
Online banner ads or pop-up ads will often be reminder ads or help-seeking ads. As such, they need not include a brief summary consistent with the current treatment of similar ads in other media. Other ads in these formats, according to the FDA, will need to disclose the brief summary information to the same extent as ads in other media. Industry has followed the FTC’s suggestion that this requirement can be satisfied by sending consumers who click on the banner ad or pop-up ad to the first Web page on the company Web site that discusses the benefits of the drug; that is, a Web page that will have the major statement of risks and an appropriate link to more complete risk information. Based on FDA’s statements in the just-released untitled letters, however, manufacturers may no longer be able to rely on the “one click” rule, and online banner ads will be treated just as “print-based” materials.20 This policy, if applied to other Internet advertising, could substantially affect Web site design and use.
Policy Issues for FDA Consideration
The Prescription Project Citizen Petition: A Call for Guidance
On December 3, 2008, the Prescription Project, a non-profit consumer healthcare advocacy organization, submitted a Citizen Petition21 to the FDA, requesting that the FDA:
- Send a letter to all “major” prescription drug and restricted medical device manufacturersstating that Internet advertising and promotion is subject to the same requirements as advertising in traditional media; and
- Issue a Draft Guidance on Consumer-Directed Broadcast Advertising of Prescription Drugs and Restricted Devices on the Internet, which would: (1) clarify that online promotions meet the definition of “broadcast advertisements” in 21 C.F.R. §§202.1(e)(1) and (l)(1); and (2) describe the requirements for online advertisements under section 502 of the FDCA.
The Prescription Project argued that the statutory and regulatory framework for broadcast advertising is sufficiently broad to govern promotional material delivered online.22 The Citizen Petition also highlighted the recent use of YouTube video ads by three medical device and drug manufacturers.23 Finally, the Prescription Project argued that manufacturers evade statutory and regulatory requirements by the use of third parties, such as marketing firms, in the placement of video content on YouTube and other interactive media. The FDA has yet to respond to this Citizen Petition.
How Will the FDA Address Advertising in New Online Applications?
Other than the warning and untitled letters discussed above, there has been little enforcement activity specifically aimed at advertising through new media. Recent comments by Kristin Davis, Deputy Director of DDMAC, at the September 2008 Food and Drug Law Institute (FDLI) Advertising and Promotion Conference do, however, indicate some areas of concern:24
- Interactive promotions such as contests in which patient users submit videos: Davis cautioned that companies would be wise to review all submissions before posting them, because the videos might be treated as testimonials, which need to be supported by substantial evidence and include risk information
- Blogs organized, supported or maintained by the manufacturer: Davis recommended monitoring or reviewing patient-generated comments before they are publicly posted on the Web site, because they also could be attributed to the manufacturer
- Promotional material posted on YouTube and other third-party sites: Davis stated that companies are responsible for company-generated material, even if it is posted on thirdparty Web sites outside the manufacturers’ control
- Wikipedia, which permits companies to contribute to, or edit, entries describing their products: Davis concluded that posting information on Wikipedia would likely be considered promotion.
As new online media evolve at an explosive pace, FDA’s inability to clarify how existing regulations apply to online advertising becomes increasingly problematic for stakeholders, including pharmaceutical companies, media companies, and consumers. Pharmaceutical companies using sites featuring user-generated content (YouTube, Wikipedia, blogs), social networking sites (Facebook, LinkedIn, MySpace), and professional networking sites (Sermo, Socrato) must carefully weigh a number of risks. Additionally, manufacturers may also be hesitant to engage with such interactive sites and applications for fear of discovering adverse events.25
To date, the FDA has applied a “paper” mentality to the Internet. This approach does not fully take into consideration how individuals interact with new technology or whether paper requirements are practical or helpful in the online arena. For all stakeholders including patients, HCPs, industry and concerned citizens, there should be a public discussion of what the new FDA standards should be and whether the old “paper” rules still fit in this dramatically changing environment.