Drug of Choice
Drug Name Size
Presentation of Information
What are the general requirements for prescription drug advertisements directed toward consumers?
The same statute and regulations apply regardless of the audience targeted by a prescription drug advertisement. The Federal Food, Drug, and Cosmetic Act (the FD&C Act) requires that all drug advertisements contain (among other things) information in brief summary relating to side effects, contraindications, and effectiveness. Because of this statutory wording, this requirement has become known as the brief summary. Typically, print advertisements include a reprinting of the risk-related sections of the product's FDA-approved labeling (also called full prescribing information or the package insert). Sponsors, however, can write this risk information in language appropriate for the targeted audience; FDA encourages this approach. In order to present useful information to consumers, FDA has recommended that certain information be provided in the brief summary while other information may be omitted. Guidance for Industry: Brief Summary and Adequate Directions for Use: Disclosing Risk Information in Consumer-Directed Print Advertisements and Promotional Labeling for Human Prescription Drugs (PDF)
In addition to the specific disclosure requirements, advertisements cannot be false or misleading or omit material facts. They also must present a fair balance between effectiveness and risk information. FDA has consistently required that appropriate communication of effectiveness information includes any significant limitations to product use.
How do prescription drug broadcast advertisements differ from print advertisements?
Current regulations specify two requirements that all prescription drug broadcast advertisements must meet. First, broadcast advertisements must include the product's most important risk-related information in the audio or audio and visual parts of the advertisement. This is sometimes called the major statement. Second, broadcast advertisements must contain either a brief summary of the advertised product's risk information, or alternatively, make adequate provision for disseminating the product's approved labeling in connection with the ad. Thus, the regulations for broadcast advertisements recognize broadcast's inherent limitations by providing an alternative mechanism for meeting the FD&C Act's information disclosure requirement.
What needs to be included as part of the major statement requirement?
The major statement must include all of the most important risk information related to the product. Because risks vary from product to product, the amount of information disclosed for any particular product to meet this requirement will vary as well.
Does FDA intend to do anything about the brief summary information? I've heard a lot of concerns about its value for consumers.
FDA has also heard concerns about the lack of value of the current approaches to present the required information from some individuals and groups. It has heard from others that consumers should get full disclosure of risk information. The agency encourages product sponsors to provide consumers with non-promotional, consumer-friendly information consistent with product labeling, along with the information required by the FD&C Act and the regulations. As mentioned above, in the case of print advertisements, FDA encourages sponsors to write their product brief summaries in consumer-friendly language and to follow other guidance, as available.
May the phrase "drug of choice" be used in advertising or promotional labeling?
The phrase "drug of choice," or any similar phrase or presentation, used in an advertisement or promotional labeling would make a superiority claim and, therefore, the advertisement or promotional labeling would require evidence to support that claim.
Does the established or proprietary name in the advertisement or brief summary have to be any particular size?
No, but the regulations specify size in sections 201.10(g)(2) and 202.1(b)(2) which state:
"The established name shall be in printed letters that are at least half as large as the letters comprising the proprietary name or designation with which it is joined, and the established name shall have a prominence commensurate with the prominence with which such proprietary name or designation appears, taking into account all pertinent factors, including typography, layout, contrast and other printing features."
Does "half as large" refer to point size or actual type size?
OPDP has interpreted "half as large" to be actual size, not point size, of upper and lower case letters in the proprietary and established drug names.
May an advertisement or labeling piece include the phrase "FDA-approved"?
Yes, if the manufacturer or sponsor has received a letter stating that the product has been approved. Effective on the date of implementation, the Food and Drug Administration Modernization Act of 1997 eliminated Section 301(l) of the Federal Food, Drug, and Cosmetic Act that prohibited "The using . . . of any representation or suggestion that approval of an application with respect to such drug or device is in effect . . . ."
How long may the word "new" be used in promotional labeling and advertisements for a newly approved product, indication, or dosage form?
OPDP generally considers that "New" is an accurate description of the marketing phase for six months from the time a product is initially marketed. This should be distinguished from the time the product is cleared by FDA for marketing.
Have there been any updates or improvements to the core launch review process?
OPDP has evaluated trends in core launch submissions over the past several years. We have also evaluated our internal business processes considering trends in prescription drug promotion submissions. In order to provide timely feedback to firms, ensure submissions are complete and reviewable, and maximize use of FDA’s resources, OPDP has added a 5-business day core launch screening period to the launch review process and provided additional clarification on what OPDP considers to be core launch materials for purposes of its review.
What is the 5-day business day core launch screening period that will occur prior to the beginning of a core launch review?
Upon receipt of a submission requesting comments on proposed core launch materials, OPDP review and project management staff will conduct a 5-business day administrative content review to determine if the submission is complete, annotated to clearly identify the source of support for each claim, and consistent with core launch parameters. Day 1 of the 5-business day core launch screening period will begin on the first business day on which the core launch submission is received by OPDP.
What information will OPDP communicate as a result of the 5-business day core launch screening period?
OPDP will notify the firm by the end of the 5-business day core launch screening period if the core launch needs an amendment, additional reference materials, or the materials are non-core launch or non-launch. Amendments and reference documents will be assigned a new 5-business day core launch screening period once received by OPDP. If there are no reasons why core launch will not commence and the core launch submission is complete and acceptable for review, OPDP will NOT contact the firm, and our review of the core launch submission will begin on the 6th business day after the core launch submission was received.
What factors will OPDP consider when assessing if materials qualify as “core” launch?
What OPDP considers to be core launch materials can be found in the guidance titled, “Providing Regulatory Submissions in Electronic and Non-Electronic Format—Promotional Labeling and Advertising Materials for Human Prescription Drugs” (OPDP Electronic Submission Guidance – Section IV.C.1).
In addition, to be within the bounds of what OPDP intends to review under the processes we describe for “core launch advisories”, those submitted materials should:
- Be limited to claims and presentations based solely on the information contained in the PI, information from the pivotal/registration trials, or publications directly related to those trials.
- Be a true representation of the core introductory messaging for the product (i.e., not a mock-up piece that includes all potential claims a firm is considering for its promotional campaign).
What does an annotated core launch piece look like?
Section VI.F.3 of the OPDP Electronic Submission Guidance describes how to annotate promotional materials. Sections VI.G.2 and VI.H of the OPDP Electronic Submission Guidance describe annotating product labeling and references, respectively. We have also included a link to an annotated mock promotional piece as an example.
If a firm’s piece presents information not contained in the PI but that may be consistent with the PI, will FDA consider the core launch advisory submission to be complete if it does not include a CFL analysis?
Yes. A core launch advisory submission will be considered complete even if it does not include analyses of the three factors described in the guidance titled, “Medical Product Communications That Are Consistent With the FDA-Required Labeling — Questions and Answers Guidance for Industry” (CFL Guidance). However, if a sponsor chooses to submit its analysis in order to support the sponsor’s assessment that the claims and/or presentations are consistent with the FDA-approved labeling, FDA will consider it.
A CFL analysis can be provided within the annotated version of the promotional piece. A mock promotional piece annotated to include a CFL analysis is linked here as an example.
If a claim or presentation is supported directly by the PI, please reference or annotate to the PI.
How do consults influence core launch advisory response times from OPDP?
Firms are reminded that if a launch advisory submission is designated as “core,” the 45-calendar day response goal does not include consultation time outside of OPDP. Materials submitted with claims and presentations not derived completely and directly from the FDA-required labeling for the product may require consultation with other experts within the FDA, which will result in a longer turnaround time for comments from OPDP. Therefore, firms should build longer overall response times into their launch implementation plans if they ask for advisory comments on core launch materials that include such claims and presentations.
How does OPDP prioritize the review of non-core launch materials?
Submission of Non-core launch materials for advisory comments is addressed Section IV.C of the OPDP Electronic Submission Guidance. While we understand that all materials are a priority for sponsors, OPDP considers non-core launch materials to be a lower priority than core launch materials. OPDP recommends that firms apply our comments on the core launch materials to non-core launch materials.
DISEASE STATE INFORMATION
Q: Would a launch promotional submission with disease state information based on references that are not the PI or registration trials/publications be considered core?
A: A launch submission that includes targeted claims or presentations of disease state information that imply a benefit or safety claim for the promoted drug should be supported by information derived from the PI, information from the pivotal/registration trials, or publications directly related to those trials to be considered core. General information about a disease state accompanied by annotations to publications such as widely-recognized disease guidelines or scientific or medical reference texts may be included in a core launch submission.
REVIEW OUTSIDE THE SCOPE OF OPDP
Q: Are CBER’s Advertising and Promotional Labeling Branch (APLB) and CDRH following the 5-business day core launch screening period as well?
A: The 5-business day core launch screening period was developed for submissions requesting comments from OPDP on proposed core launch materials. If you have questions or need information about launches for APLB or CDRH products, please contact them directly.
INITIATION OF THE 5-BUSINESS DAY CORE LAUNCH SCREENING PERIOD
Q: How does FDA determine the receipt date that initiates the 5-business day core launch screening?
A: Please refer to the guidance for industry titled Providing Regulatory Submissions in Electronic Format – Receipt Dates for more information on how FDA determines the date of receipt for regulatory submissions.
Does it matter where a package insert is placed on a labeling piece, such as on a calendar or a brochure with a pouch?
The package insert is required to accompany the labeling piece.
Are package inserts required in all labeling pieces for products that are the same except for different strengths or dosages?
Yes. Even though products may be very similar, package inserts may be different for different dosage forms or different delivery systems for the same drug. The regulations require a package insert for each dosage form and delivery system for which claims appear in the promotional labeling piece. Some drug products, however, have multi-dosage form package inserts. In those cases, the same package insert could be attached to each piece, even if the dosage forms or delivery systems were different.
Does a package insert in another language also have to be submitted in English?
Yes. Package inserts have to be submitted in English and not only in the foreign language.
Where do the regulations state the requirement for submitting prescription drug advertisements and labeling?
Under 21 C.F.R. 314.81(b)(3)(i):
Section 314.81 Postmarketing reports.
(b) Reporting requirements. The applicant shall submit to the Food and Drug Administration at the specified times two copies of the following reports:
(3) Other reporting--(i) Advertisements and promotional labeling. The applicant shall submit specimens of mailing pieces and any other labeling or advertising devised for promotion of the drug product . . . .
(See Selected Provisions of the Regulations for the entire paragraph.)
When do promotional materials need to be submitted to OPDP?
Pursuant to 314.81(b)(3)(i), submissions must be made " . . . at the time of initial dissemination of the labeling and at the time of initial publication of the advertisement for a prescription drug product."
Do all promotional materials for prescription drugs have to be submitted to OPDP?
The regulations for submitting materials apply to holders of NDAs, ANDAs, and antibiotic applications. Manufacturers of pre-1938 products and products that have been declared "not new drugs" are not required to submit specimens. All products have labels and prescribing information, however, and products without approved labeling have permitted labeling. Permitted labeling indicates FDA agrees with the label or labeling and permits its use. A manufacturer of a product with "permitted" labeling is responsible for assuring that advertisements and promotional labeling pieces are consistent with the product labeling.
What form should applicants use to submit materials to FDA?
Form FDA 2253 Transmittal of Advertisements and Promotional Labeling for Drugs for Human Use.
How can I obtain a Form FDA-2253?
To whom should I send the materials?
Please see draft guidance entitled Providing Regulatory Submissions in Electronic and Non-Electronic Format - Promotional Labeling and Advertising Materials for Human Prescription Drugs for information on how to submit. FDA began accepting eCTD submissions using the new M1 specifications June of 2015.
Who is responsible for submitting a Form FDA-2253 if the manufacturer and distributor are different companies?
Either company may submit the specimens, however, the applicant is ultimately responsible for compliance with 21 CFR 314.81(b)(3).
Can the layout or the way information is presented affect whether an advertisement or labeling piece is in compliance with the regulations?
Yes, 21 CFR 202.1(e)(7)(viii) states that an advertisement may be false, lacking in fair balance, or otherwise misleading if it:
"Fails to present information relating to side effects and contraindications with a prominence and readability reasonably comparable with the presentation of information relating to effectiveness of the drug, taking into account all implementing factors such as typography, layout, contrast, headlines, paragraphing, white space, and any other techniques apt to achieve emphasis."
For example, the presentation below of the word benefits and the word disadvantages would not be considered comparable. Although the words are the same point size, the color and contrast with the background make the word benefits much more noticeable than the word disadvantages.
What is the turn-around time for press-releases requested by sponsors?
Generally, there is a 2 working day turn-around for the review of draft press releases when requested by sponsors. This 2 working day turn-around timeframe typically applies to press releases that only reference the prescribing information (PI). For press releases that include references outside the PI and/or require consultation, we will notify the sponsor and treat that press release as a regular launch or non-launch advisory submission.
Does FDA "approve" advertisements and promotional labeling before use by the company?
No, pre-approval of promotional materials is not required except in rare instances. For example, FDA may require pre-approval of promotional materials as part of a compliance action. However, OPDP provides opinions on proposed advertisements and labeling pieces before use upon request by an applicant. Note that accelerated approval products are under a "presubmission" requirement. The accelerated approval regulations require that applicants submit to FDA copies of all promotional materials prior to the intended date of dissemination or publication.
What is a reminder advertisement?
Under 202.1(e)(2)(i), reminder advertisements are identified as an exemption to the advertisement regulations, including the provisions under 202.1(e) to provide a brief summary. Reminder advertisements " . . . call attention to the name of the drug product but do not include indications or dosage recommendations for use of the drug product. . . . and, optionally, information . . . containing no representation or suggestion relating to the advertised drug product." Reminder advertisements cannot make a representation about the product or suggest a use for the product.
What is reminder labeling?
Under 201.100(f), reminder labeling is " . . . labeling which calls attention to the name of the drug product but does not include indications or dosage recommendations for use. . . . and, optionally, information . . . containing no representation or suggestion relating to the drug product." Reminder labeling is exempted from the provisions under 201.100(d) to provide the full prescribing information.
Does FDA limit the amount of money that can be spent on reminder advertisements or reminder labeling pieces or regulate the types of objects (such as pens, cups, calendars, etc.) that can be used as reminder advertisements or reminder labeling pieces?
FDA regulations do not limit how much money companies may spend on reminder advertisements and labeling pieces, nor do the regulations limit the types of objects that can be used. The regulations, however, limit the type of information that can be presented in reminder advertisements and labeling pieces, written information, and in graphics, design, or some other visual representation.
Are the advertising and labeling procedures for orphan drugs and regular NDA products the same?