Some claim that DTC advertising leads to increased use of products that are not always appropriate or medically necessary for patients. However, a recent study from the Food and Drug Administration (FDA) looking at the power of background visuals to distract viewers from the often-ominous risk info read in the “major statement” section of TV drug ads found no evidence that consumer understanding of risk info is affected by the “emotional (affective) tone of images.”
Nevertheless, to address the mounting concerns from consumer groups, anti-industry organizations, and Congress, FDA recently released a Draft Guidance for Industry, entitled “Direct-to-Consumer Television Advertisements – FDAAA DTC Television Ad Pre-Dissemination Review Program.”
Comments on the Draft Guidance are due May 14, 2012, Docket No. FDA–2012–D–0022.
The guidance is intended to assist sponsors of human prescription drugs, including biological drug products approved under section 351 of the Public Health Service Act, by describing how FDA plans to implement the requirement for the pre-dissemination review of DTC television advertisements (TV ads) according to section 503B of the Federal Food, Drug, and Cosmetic Act (the FD&C Act). The guidance describes the types of TV ads that FDA intends to be subject to this provision, explains how FDA will notify sponsors that an ad is subject to the requirement of review under section 503B, and describes the general and Center-specific procedures sponsors should follow to submit their TV ads to FDA for pre-dissemination review in compliance with section 503B of the FD&C Act.
Former FDA Attorney Arnold Fried noted that the new guidance “seems to mandate submission of virtually all DTC TV advertising in virtually all contexts.” While some ads may escape mandatory “because they are simply follow-on's of already pre-reviewed ads and nothing about the drug's safety or effectiveness has changed in the meantime,” Friede said that ads not subject to mandatory prereview will be the exception rather than the rule.”
In addition, Fried noted that, “Given the substantial volume of reviews under the new mandatory program, coupled with the absence of any money available to FDA from the voluntary, user fee funded program,” there are significant concerns about FDA’s “ability to undertake the new mandatory review program and meet the 45 day review time table.” He also raised concerns that this guidance might raise regarding commercial speech under the First Amendment.
The proposed “guidance” demonstrates the importance of the Prescription Drug User Fee Act (PDUFA) V negotiations, which must be reauthorized by Congress this fall, said John Kamp, Executive Director of the Coalition for Healthcare Communication. Kamp noted that FDA’s guidance is merely implementing provisions from 2007 PDUFA IV reauthorization. However, as Fried pointed out, “Congress failed to authorize FDA to collect user fees under the voluntary program and that program effectively died. See FDA Federal Register Notice, DTC User Fee Program Will Not Be Implemented (January 16, 2008).
“On the face of it, FDA is not being punitive, just being very careful to follow its legislative mandate,” Kamp added. He recognized, however, that “the devil will be in the enforcement details.” Kamp noted that the “guidance creates an FDA “shot clock” that doesn't allow you to take a shot at broadcast marketing for an additional 45 days. And, unfortunately, there is no "overtime" tacked on at the end of the patent period to recoup the lost sales opportunity.”
Background of FDA and DTC
On September 27, 2007, the President signed into law the Food and Drug Administration Amendments Act of 2007 (FDAAA) (Public Law No. 110-85). FDAAA gives FDA the authority to “. . . require the submission of any television advertisement for a drug . . . not later than 45 days before dissemination of the television advertisement” (section 901(d)(2), codified at 21 U.S.C. 353b).
In conducting a review of a TV ad under this section, FDA may make recommendations with respect to information included in the label of the drug on:
- changes that are necessary to protect the consumer good and well-being, or that are consistent with prescribing information for the product under review; and
- statements for inclusion in the advertisement to address the specific efficacy of the drug as it relates to specific population groups, including elderly populations, children, and racial and ethnic minorities, if appropriate and if such information exists. 21 U.S.C. 353b(b)(1) and (2).
FDA intends to require sponsors to submit TV ads for pre-dissemination review in the following categories:
- Category 1: The initial TV ad for any prescription drug or the initial TV ad for a new or expanded approved indication for any prescription drug
- Category 2: All TV ads for prescription drugs subject to a Risk Evaluation and Mitigation Strategy (REMS) with elements to assure safe use (see section 505-1(f) of the FD&C Act)
- Category 3: All TV ads for Schedule II controlled substances
- Category 4: The first TV ad for a prescription drug following a safety labeling update that affects the Boxed Warning, Contraindications, or Warnings & Precautions section of its labeling
- Category 5: The first TV ad for a prescription drug following the receipt by the sponsor of an enforcement letter (i.e. a Warning or untitled letter) for that product that either cites a TV ad or causes a TV ad to be discontinued because the TV ad contained violations similar to the ones cited in the enforcement letter
- Category 6: Any TV ad that is otherwise identified by FDA as subject to the predissemination review provision
These categories reflect a risk-based approach that will enable FDA to leverage its limited resources to best protect the public health by ensuring that certain high risk and high impact TV ads accurately and effectively communicate key information about advertised products, including their major risks and indications. Specifically, these categories allow FDA to review and provide comments on TV ads for prescription drugs with particularly serious risks, and to review and provide comments on TV ads at times when feedback on the risk and indication communication in the ad is particularly critical, including when a product is first advertised on TV and after a product has received a significant safety labeling update or a new or expanded indication.
Category # 1: FDA intends to review and comment on the first TV ad for a prescription drug or the first TV ad for a new or expanded indication for an already-approved product. This will allow FDA to provide feedback on the major statement (i.e., the presentation of risk information in a broadcast ad), which sponsors can apply to both the initial ad and future ads. FDA can also identify any issues with the presentation of the product’s indication and, where applicable, the product’s specific efficacy in population subgroups, and provide feedback relevant to both current and future ads.
Categories # 2 and # 3: FDA intends to review all TV ads for certain prescription drugs with particularly serious risks relative to benefits — specifically, products with REMS with elements to assure safe use and products that are Schedule II controlled substances. FDA believes it is critically important that the risks associated with such products be appropriately communicated in all promotion, and intends to review all TV ads for such products to help ensure that this occurs.
Category # 4: FDA intends to review and comment on the first TV ad for a prescription drug following a significant safety labeling update to the product’s FDA-approved prescribing information (PI). This will allow FDA to provide feedback on the “major statement” for that product to help ensure that new risk concepts are communicated appropriately in the submitted ad and in future ads for the product.
FDA understands that certain safety labeling supplements can be submitted as “Changes Being Effected” supplements (CBE supplements), and that sponsors may begin distribution of the product using the modified labeling contained in the supplement upon receipt of the CBE supplement by FDA. If a sponsor chooses to disseminate a TV ad while such a CBE supplement is pending review and approval by FDA, FDA encourages the sponsor to submit the TV ad under the voluntary advisory review process to the appropriate group (OPDP or APLB).
Once FDA has approved the CBE supplement (resulting in a significant safety update to the product’s FDA-approved labeling), FDA intends to require the sponsor to submit its next TV ad for the product to FDA for pre-dissemination review, even if the same or a substantially similar TV ad was submitted voluntarily prior to the FDA approval of the CBE supplement, to ensure that the ad remains consistent with the labeling as approved.
Category # 5: FDA intends to review and comment on the first TV ad for a prescription drug after a sponsor receives an enforcement letter from FDA for its promotion of that product that either cited a TV ad or caused a TV ad to be discontinued because the TV ad contained violations similar to the ones cited in the enforcement letter. In either of these cases, FDA intends to review the next TV ad for the product before it is publicly aired to ensure that the ad is not false or misleading and that the ad does not contain violations that are the same or similar to those cited in the enforcement letter.
Category # 6: In addition, FDA may notify a sponsor that a TV ad for a product is subject to the pre-dissemination review provision in the FD&C Act if such pre-dissemination review is deemed necessary from a public health perspective. This would be done on a case-by-case basis after considering the risks associated with particular products. In such a case, a sponsor will be notified in writing of our decision to apply this provision to its product and of the length of time that the pre-dissemination review requirement will be in effect for its product.
Generally, sponsors have the option of submitting any proposed prescription drug television ad to FDA for advisory review before publicly disseminating the ad (see 21 CFR 202.1(j)(4)). In this way, sponsors can benefit from FDA’s input on whether or not ads are accurate, balanced, and nonmisleading before they disseminate the ads. This voluntary submission process also gives sponsors an opportunity to address any problems before the TV ads are shown to the public, improving the quality of the ads.
This voluntary submission process is still available to sponsors. However, if a sponsor has been notified that a TV ad for one of its products is subject to the pre-dissemination review provisions in section 503B of the FD&C Act, it will be required to submit this TV ad for pre-dissemination review.
FDA understands that sponsors subject to the 503B pre-dissemination review provision may revise their TV ads after receiving comments from the Agency, but before disseminating the ads. FDA does not expect a sponsor to resubmit its draft TV ad for pre-dissemination review if the revisions made to the ad are in response to the Agency’s comments and do not introduce new claims, concepts, or creative themes into the TV ad. If a sponsor does wish to request additional comments on such a TV ad, it should do so under the voluntary advisory submission process.
However, if a sponsor revises a draft TV ad following pre-dissemination review under section 503B to add new claims, concepts, or creative themes into the TV ad, the sponsor will be required to resubmit the TV ad to the Agency for pre-dissemination review following the procedures outlined in this guidance.
FDA intends to notify drug sponsors of the requirement to submit their TV ads for pre-dissemination review in several different ways. For drugs approved in the future and for approved drugs for which an expanded indication is approved in the future (Category 1), for approved drugs that fall under Categories 4 and 5 as described in this guidance, and for any other drugs for which FDA determines pre-dissemination review of TV ads is required (Category 6), FDA intends to notify sponsors in the letter approving the application or supplement, in the approval of the labeling update, in the enforcement letter, or in other correspondence.
For drugs already approved prior to the issuance of this guidance that fall under Categories 1, 2, and 3, FDA intends to publish a notice in the Federal Register notifying sponsors that their products will be subject to pre-dissemination review in accordance with section 503B of the FD&C Act. However, if a sponsor is developing a TV ad for a product that falls into one of the categories described above and has not yet received written notification, FDA recommended that the sponsor submit the TV ad for pre-dissemination review as described in this guidance.
Sponsors must include in all pre-dissemination review packages for a TV ad:
1. A cover letter that:
- Provides the following subject line: Pre-Dissemination Review Package for a Proposed TV Ad for [Proprietary Name/Established Name (dosage form) (for drugs), or Trade name/Proper name (for biologics)] Subject to 503B of the FD&C Act
- Includes the NDA or STN number
- Provides the name of the proposed TV ad
- Lists the contents of the pre-dissemination review package and the number of copies provided of each item contained in the pre-dissemination review package
- Provides a sponsor contact’s name, title, address, phone, fax, and email
2. Annotated storyboard of the proposed TV ad to show which references support which claims
3. The most current FDA-approved prescribing information (PI) and, if applicable, the FDA-approved patient labeling or Medication Guide with annotations cross-referenced to the storyboard
A sponsor should also include appropriate documentation, if any of the following apply:
4. Annotated references to support product claims not contained in the PI, cross-referenced to the storyboard
5. Verification that a person identified in a TV ad as an actual patient or health care practitioner is an actual patient or health care practitioner and not a model or actor; and/or Verification that a spokesperson who is represented as a real patient is indeed an actual patient; and/or Verification that an official translation of a foreign language TV ad is accurate
6. Annotated references to support disease or epidemiology information, cross-referenced to the storyboard
7. A video of the TV ad in an acceptable format, if available. FDA cannot provide final comments on the acceptability of a TV ad without viewing a final recorded version in its entirety. FDA understands that some sponsors may wish to receive comments from the Agency before producing a final recorded version of the ad. In such situations, sponsors can submit a pre-dissemination review package without a final recorded version of the ad, but once the final recorded version is produced, it will need to be submitted to the Agency for pre-dissemination review.
FDA stated that materials unrelated to a proposed TV ad being submitted for pre-dissemination review should not be included in the pre-dissemination review package. For example, manufacturers should not include other draft promotional materials in the pre-dissemination review package. In addition, only one proposed TV ad should be submitted per pre-dissemination review package.
If FDA receives an incomplete package, FDA will:
- Inform the sponsor that the submission is incomplete
- Provide the reason(s) that the package is incomplete
- Request a submission package that contains the missing materials
Frequently Asked Questions
Under section 503B, FDA may require that a TV ad be submitted to FDA for review not later than 45 days before the sponsor intends to disseminate the ad (21 U.S.C. 353b(a); see also 21 U.S.C. 333(g)(3)(C)). The 45-day review clock for proposed DTC TV ads subject to the pre-dissemination review provision begins when CDER or CBER has received a complete pre-dissemination review package from a sponsor.
If FDA is not able to complete its review within the 45-day time frame, FDA will notify the sponsor. FDA’s notification will include an estimate of the date on which FDA expects to provide its comments. In such situations, the sponsor should determine whether it will wait for FDA’s comments before disseminating the TV ad or whether it will disseminate the TV ad without waiting for FDA’s comments. The sponsor should notify FDA of its decision.
Once the 45-day review time has elapsed, there is no specific legal consequence resulting from disseminating the proposed TV ad without waiting for FDA’s comments. However, once an ad is disseminated, the sponsor is at risk of enforcement action if the ad violates the FD&C Act and implementing FDA regulations.
If a sponsor decides to disseminate the proposed TV ad before receiving FDA’s comments, but after the 45-day clock has run, FDA will discontinue its 503B review. If the ad is disseminated, the sponsor is at risk of enforcement action if the ad violates the FD&C Act and implementing FDA regulations.
Under section 301(kk) of the FD&C Act (21 U.S.C. 331(kk)), dissemination of a television advertisement without complying with section 503B is a prohibited act. This prohibited activity can be enjoined (21 U.S.C. 332(a)) and be subject to criminal penalties (21 U.S.C. 333(a)). In addition, if FDA assesses civil monetary penalties to the sponsor because the TV ad is false or misleading (21 U.S.C. 333(g)). In determining the civil monetary penalty amount, FDA will take into account
- The fact that the sponsor failed to submit a TV ad for pre-dissemination review that was required to be submitted under section 503B (21 U.S.C. 333(g)(3)(B)),
- The fact that the sponsor, after submitting the ad, disseminated the ad before the end of the 45-day comment period (21 U.S.C. 333 (g)(3)(C)).
- The fact that the sponsor failed to submit the TV ad for pre-dissemination review or disseminated it after submission but before the 45-day comment period without waiting for comments from FDA if it decides to issue an untitled letter or Warning letter to the sponsor for the TV ad.
Under section 503B(e), FDA may require specific disclosure of a serious risk listed in the labeling of a drug, and may require the ad to include the date of the product’s approval for a period of up to 2 years after that approval, where the absence of either of these pieces of information would render the ad false or misleading. Failure to incorporate these specific required disclosures is a prohibited activity under section 301(kk) that can be enjoined (21 U.S.C. 332(a)) and be subject to criminal penalties (21 U.S.C. 333(a)).
As a result of its review, in addition to requiring disclosures as described above, FDA may also provide comments indicating other elements of the TV ad that it believes would result in the ad being false or misleading, or otherwise violating the FD&C Act or implementing regulations. If FDA assesses civil monetary penalties to the sponsor because it has disseminated a TV ad that is false or misleading (21 U.S.C. 333(g)), in determining the civil monetary penalty amount, FDA will take into account
- The fact that the sponsor disseminated the TV ad without incorporating the FDA’s comments (21 U.S.C. 333(g)(3)(D)).
- The fact that the sponsor disseminated the TV ad without incorporating the FDA’s comments if it decides to issue an untitled or Warning letter.
On the positive side, Fried noted that the Guidance creates “a substantiation dossier identifying the claims in the advertisement and the supporting evidence,” which is similar to the FTC regulations and has some “practical advantages because it allows the sponsor to lay out its case to FDA about why the proposed advertising meets all applicable requirements.” He asserted that this requirement will give “a company a good opportunity to lay out its arguments and analysis for why the risk information in the advertising complies with the major statement fair balance rules, and why, in the words of section 502(n) as amended by FDAAA, the major statement is presented in a clear, conspicuous, and neutral manner.”