The FDA released final guidance Dec. 26 with the answers to 10 questions regarding the final rule the agency released in November concerning the major statement in a direct-to-consumer (DTC) TV or radio advertisement that states the name of the drug and its conditions of use.

The guidance addresses the content and effect of the final rule, including identifying which drugs and advertisements are covered by the rule. In addition, it explains when companies are expected to comply with the final rule and how they can do so. The rule covers manufacturers, packers and distributors of any human prescription drug that, in any state, is distributed or offered for sale and who advertise that drug, and to all persons who they cause to issue any advertisement with respect to their human prescription drug(s), including both individuals and corporate entities.

The guidance noted the standards established by the final rule apply to advertisements for human prescription drugs that:

• Are presented directly to consumers;
• Are in television or radio format; and
• State the name of the drug and its condition(s) of use.

In addition, the content of the major statement (e.g., the major side effects and contraindications) is not changed by this final rule.

As to how companies can know whether its major statement is presented in a clear, conspicuous and neutral manner, the guidance said the FDA established five standards:

• The major statement is presented in consumer-friendly language and terminology that is readily understandable (21 C.F.R. §202.1(e)(1)(ii)(A));
• The major statement’s audio information, in terms of the volume, articulation and pacing used, is at least as understandable as the audio information presented in the rest of the advertisement (21 C.F.R. §202.1(e)(1)(ii)(B));
• In advertisements in television format, the major statement is presented concurrently using both audio and text (dual modality). To achieve dual modality: either the text displays the verbatim key terms or phrases from the corresponding audio, or the text displays the verbatim complete transcript of the corresponding audio; and the text is displayed for a sufficient duration to allow it to be read easily. The duration is considered sufficient if the text display begins at the same time and ends at approximately the same time as the corresponding audio (21 C.F.R. §202.1(e)(1)(ii)(C));
• In advertisements in television format, for the text portion of the major statement, the size and style of font, the contrast with the background, and the placement on the screen allow the information to be read easily (21 C.F.R. §202.1(e)(1)(ii)(D)).
• During the presentation of the major statement, the advertisement does not include audio or visual elements, alone or in combination, that are likely to interfere with comprehension of the major statement (21 C.F.R. §202.1(e)(1)(ii)(E)).

To meet the first standard (21 C.F.R. §202.1(e)(1)(ii)(A)), companies “must use consumer-friendly language and terminology that is readily understandable, rather than medical or technical jargon or terms usually more familiar to health care providers,” the guidance said. In addition, companies “must also avoid language or terminology in the presentation of the major statement that is so vague as to be readily subject to different interpretations.” However, the final rule “does not require the use of language associated with a particular grade level of reading or similar criterion, as FDA recognizes that it may be necessary to include certain terms in the major statement (e.g., a reference to a disease like “tuberculosis”) that could result in a relatively high grade level rating.”

The standard also requires that the risk information is understandable to the ordinary consumer while providing companies with flexibility in designing their DTC TV/radio ads.

To comply with the second standard (21 C.F.R. §202.1(e)(1)(ii)(B)), companies should consider the volume, articulation, and pacing of the audio presentation of the major statement in the advertisement to ensure that the audio presentation of the major statement is as understandable as or more understandable than the audio presentation of other information in the advertisement.

To meet the third standard for dual modality (21 C.F.R. §202.1(e)(1)(ii)(C)), “either the text displays the verbatim key terms or phrases from the corresponding audio, or the text displays a verbatim complete transcript of the corresponding audio; and the text is displayed for a sufficient duration to allow it to be read easily,” the guidance said, adding “the duration is considered sufficient if the text display begins at the same time and ends at approximately the same time as the corresponding audio.” Companies have flexibility in determining how they choose to comply with the first prong of this standard. They can either use text to display key words or phrases, using the same words used in the corresponding audio presentation of the major statement (not synonyms), or they can display a complete transcript of the corresponding audio, using the same words used in the corresponding audio. “For example, if the audio states: ‘the most common side effects of DRUG X are dry mouth, headache, and heartburn,’ the firm could display the full transcript of that statement as shown. The firm could also display: ‘dry mouth, headache, heartburn.’”

In addition, a company also must ensure that the display of textual information in the major statement appears for a sufficient duration to allow it to be read easily. “The regulation provides that this requirement is met if the ad begins displaying the major statement text at the same time that the corresponding major statement audio information begins and stops displaying the text at approximately the same time that the corresponding audio information ends,” the guidance said. “Note that the pacing of the audio presentation of the major statement must enable the ad to satisfy Standard 2 (21 CFR 202.1(e)(1)(ii)(B)).”

The guidance noted the fourth standard (21 C.F.R. §202.1(e)(1)(ii)(D)) “applies to the presentation of the major statement and not to other textual information in the advertisement. To comply with this standard, firms are required to ensure that the presentation of the text of the major statement is easily readable,” the guidance said.

However, companies are not required to use particular font colors, sizes, placement or backgrounds but instead are required to ensure that these aspects of text in combination result in an easily readable presentation of the major statement. “More than one combination may allow for the textual information to be read easily,” the guidance said. “For example, increasing the amount of contrast between the font and the background may improve readability. And, even at a smaller size, some styles of font are more easily read compared to others.”

The guidance noted the fifth standard (21 C.F.R. §202.1(e)(1)(ii)(E)) “applies only to the portion of the advertisement during which the major statement is presented. To comply with this requirement, firms must ensure that their DTC TV/radio ads do not include audio or visual elements (music, sounds, text, images, etc.) during the presentation of the major statement that, alone or in combination, are likely to interfere with comprehension of the major statement,” the guidance said. “Not all audio or visual elements are likely to interfere with comprehension of the major statement. In fact, by requiring dual modality – the concurrent use of both text (a visual element) and audio to present the major statement in advertisements in TV format – the final rule acknowledges that multiple elements can actually be used to reinforce risk information. This standard does not categorically prohibit use of other creative elements during the major statement. It also does not prohibit narrower categories of elements (e.g., it does not bar all music, sound effects, drawings). The standard does not even categorically prohibit any subtypes of elements (e.g., it does not bar upbeat music or amusing drawings),” the guidance said, concluding that companies “should examine the facts and circumstances presented by a specific advertisement to ensure that the advertisement complies with this standard.”

The guidance also noted companies can voluntarily request comments from the FDA on proposed DTC TV/radio ads before dissemination. Reviewers in FDA’s Office of Prescription Drug Promotion (OPDP) within the Center for Drug Evaluation and Research (CDER) and reviewers in the Advertising and Promotional Labeling Branch (APLB) within the Center for Biologics Evaluation and Research (CBER) will evaluate the draft materials that companies submit for, among other things, compliance with the final rule and provide comments to companies for their consideration.