Released by FDA: 11/19/02.  Posted by FDA:  11/26/02

Sharon L. Camp, Ph.D.
President and CEO
Women's Capital Corporation
1990 M Street, NW
Suite 250
Washington, DC 20036

RE:     NDA 21-045
          Plan B (levonorgestrel) Tablets, 0.75 mg
          MACMIS ID # 11214

Dear Dr. Camp:

This letter concerns Women's Capital Corporation's (WCC) direct-to-consumer (DTC) broadcast and print advertisements (ads) for Plan B (levonorgestrel) Tablets for emergency contraception.  These ads were disseminated by radio broadcast (60 second "Jane's Lucky Day") airing on selected Seattle, Washington radio stations and by publication as a full-page print ad ("'Oops" and "Uh-oh"') appearing in the Seattle Weekly.  The Division of Drug Marketing; Advertising, and Communications (DDMAC) has reviewed these ads as part of its monitoring and surveillance program.

DDMAC has concluded that WCC's ads are false, lacking in fair balance, or otherwise misleading in violation of the Federal Food, Drug, and Cosmetic Act (Act) and applicable implementing regulations.  Specifically, the DTC radio and print ads overstate efficacy, fail to convey important limitations on use, and minimize important information about risks associated with the use of Plan B Tablets emergency contraception.  As a result, the ads raise significant public health and safety concerns.

Background

Plan B is an emergency contraceptive prescription drug product approved to prevent pregnancy after unprotected sex, such as intercourse without contraception or when a contraceptive fails. Plan B is approved "for emergency use, and should not be used in place of regular contraception since it is not as effective as regular contraceptives." (See Plan B approved patient labeling).  Similarly, a Bolded Warning in the Plan B approved physician labeling (PI) states: "Plan B is not recommended for routine use as a contraceptive...."  The Clinical Trials section of the PI also states that "[e]mergency contraceptives are not as effective as routine contraception."  Moreover, the PI stresses that, "[t]o obtain optimal efficacy," (the greatest likelihood of preventing an unintended pregnancy), "the first tablet should be taken as soon as possible within 72 hours of intercourse.  The second tablet must be taken 12 hours later." (emphasis added) (See the Indications & Usage and Dosage and Administration sections)

A patient considering use of Plan B emergency contraception should be informed not only of these limitations on efficacy, and the importance of using the product promptly, but also of the potential risks associated with use of the product.  A patient needs to be informed that she should not use Plan B if she has unexplained vaginal bleeding or if site is already pregnant, and that Plan B does not protect against HIV infection (AIDS) or other sexually transmitted diseases (STDs).  She must also be aware that severe abdominal pain can signal the possibility of a serious medical condition (i.e., tribal (ectopic) pregnancy) requiring immediate medical intervention.

False or Misleading Efficacy Presentations -- Overstatement of Efficacy

Prescription drug ads are false or misleading if they suggest that a prescription drug is more effective than has been demonstrated by substantial evidence or substantial clinical experience (21 CFR 202.1(e)(6)(i)).  The totality of claims and presentations in the radio and print ads misleadingly overstates the efficacy of Plan B.  The radio ad claims that "[I]t's Jane's lucky day, all right.  Because she still has 72 hours after unprotected sex to prevent pregnancy with Plan B emergency contraception.  Similarly, the print ad claims, "Find out how Plan B, taken within 72 hours of intercourse, can be your back-up plan in preventing pregnancy.  And find yourself uttering phrases like 'Phew!"'  These unqualified characterizations suggest that Plan B is guaranteed to prevent the risk of unintended pregnancy every time, and they also fail to convey that Plan B is for emergency use only because Plan B is not as effective as routine contraceptives.

Specifically, statements such as "she still has 72 hours after unprotected sex to prevent pregnancy" and "Taken within 72 hours of intercourse" misleadingly suggest that a woman could take Plan B as late as three days after unprotected intercourse with the same likelihood of reducing the risk of unintended pregnancy.  Thus, the ads fail to clearly communicate a crucial limitation to the effective use of Plan B, that it must be used as soon as possible.  By presenting the 72 hour limitation as a product benefit rather than a limitation to its use, the Plan B ads fail to adequately convey, and indeed undermines, this crucial efficacy-related prescribing information.

Furthermore, the radio and print ads are misleading because they do not clearly communicate the indication and limitation of use for Plan B as emergency contraception after unprotected sex.  The ads omit context and therefore minimize material facts in light of representations made about preventing unintended pregnancy by failing to explain that Plan B is for emergency use only because it is less effective than routine contraception methods.  Without this important contextual information, women may be misled into believing that, contrary to the approved labeling, Plan B can be used for routine contraception.

Minimization of Important Risk Information

The Act requires that all prescription drug advertisements include a true statement of information in brief summary relating to side effects, contraindications (including warnings, precautions, etc.), and effectiveness (21 U.S.C. 352(n)), commonly referred to as the "brief summary."  However, the regulations distinguish print ads from broadcast ads in fulfillment of the "brief summary" requirement (21 CFR 202.1(e)(1)).  Print ads must present a brief summary, which contains each specific side effect and contraindication from the product's approved labeling (PI).  Ads broadcast through media, such as television or radio, are required to contain a brief seminary or, alternatively, make "adequate provision" for the dissemination of the PI in connection with the broadcast presentation.  The regulations also require that broadcast ads include information relating to the major side effects and contraindications of the advertised drug in either the audio or audio and visual parts of the broadcast presentation, commonly referred to as the "major statement."  The content and presentation of the radio and print ads misleadingly minimize or omit important risk information:  Consequently, the ads misleadingly suggest that Plan B is safer than has been demonstrated by substantial evidence or substantial clinical experience (21 CFR 2011(c)(6)(i)).

Radio Ad

The radio ad directive "Call your doctor right away if you have severe abdominal pain" fails to provide sufficient context to explain that it is important that the woman contact her doctor immediately because severe abdominal pain may signal a serious medical condition, i.e., a tubal (ectopic) pregnancy, which can be life-threatening.  Furthermore; the radio ad fails to disclose the significant public health message included in the Precautions section of the PI that Plan B will not protect against HIV infection (the virus causing AIDS) or any other sexually transmitted disease.  Accordingly, this should be included as part of the "major statement."

The radio ad also fails to present the information relating to major side effects and contraindications (including warnings and precautions) with a prominence and comprehension reasonably comparable with the effectiveness claims in the ad (21 CFR 202.1(e)(7)(viii)).  The faster pacing of the announcer audio presenting the risk information (as is explicitly directed by the script; "faster") is read at a speed at which the risk information is not likely to be understood, much less comprehended, by the typical consumer.  Moreover, the description of the most serious risks associated with use of Plan B is not as audible or as well articulated as the effectiveness audio presentation.  Therefore, the ad is misleading because of this unbalanced presentation of effectiveness versus serious risk information.

Print Ad

The print ad lacks fair balance and is misleading because if fails to present information about the risks associated with the use of Plan B with a prominence and readability reasonably comparable to the presentation of information relating to the effectiveness of the drug, taking into account all implementing factors (21 CFR 202.1(e)(7)(viii)).

The only risk information included in the one-page print ad is presented on the bottom half of the newspaper page as an accompanying "brief summary" of risk information.  By contrast, effectiveness claims like "Phew! ACCIDENTS HAPPEN.  That's why there's Plan B." are presented in much larger type and highlighted in a box.  The presentation of risk information in very small type across three columns is not reasonably comparable, in either readability or prominence, to the ad's presentation of Plan B's effectiveness. Furthermore, the print ad conveys the effectiveness information in consumer-friendly language; but does not convey the risk information in comparably consumer-friendly language.  Therefore, the ad is misleading because of this unbalanced presentation of product benefits versus risk information.

Failure to Disclose Established Drug Name

The print and radio ads fail to disclose the established drug name (levonorgestrel) in the ad. Prescription drug ads are required to include the established drug name (21 USC 352 (n)).

Failure to Make Adequate Provision for Dissemination of the PI

The prescription drug advertising regulations require sponsors of broadcast ads to present a brief summary or, alternatively, make "adequate provision ... for dissemination of the approved or permitted package labeling in connection with the broadcast presentation" (21 CFR 202.1(e)(1)).

The Plan B radio ad does not contain a brief summary.  Consequently, the regulations require that adequate provision be made for dissemination of the (PI) in connection with the ad. The radio ad states, "To find a pharmacist in Washington who provides Plan B, call 1-866-TURN TO PLAN B or visit www dot go to plan b dot com.  For more information, see our ad in the Seattle Weekly."  The statement "To find a pharmacist in Washington who provides Plan B, call....or visit www...." (emphasis added), fails to clearly communicate that the telephone number, website address, and pharmacist are ways to access the approved product labeling and additional product information.

Conclusions and Requested Actions

WCC should immediately cease dissemination and distribution of these and other similar promotional materials for Plan B that contain the same or similar claims or presentations. Please submit a written response to DDMAC on or before December 4, 2002, describing your intent and plans to comply with the above.  In its letter to DDMAC, WCC should include the date on which these and other similarly violative materials were discontinued.

WCC should direct its response to the undersigned by facsimile at (301) 594-6'7'71, or at the Food and Drug Administration, Division of Drug Marketing, Advertising, and Communications HFD-42, Rm. 8B-45, 5600 Fishers Lane, Rockville, Maryland 20857. I n all future correspondence on this matter, please refer to MACMIS ID# 11214 as well as the NDA number.  DDMAC reminds WCC that only written communications are considered official.

Sincerely,

Joan Hankin
Consumer Promotion Analyst
Division of Drug Marketing,
    Advertising, and Communications