1. Information about Rx Drugs: Regulatory and Marketing Issues Ilisa B.G. Bernstein, Pharm.D., J.D. Director of Pharmacy Affairs U.S. Food and Drug Administration May 2009

2. Objectives Understand legal and regulatory system for drug advertising and promotion Identify FDA initiatives designed to increase transparency and provide improved access to data on prescription drugs. Discuss recent enforcement actions

3. Overview Law/regulations/guidance Statistics FDA medical product promotion website Direct-to-consumer advertising Sources of drug information

4. Labeling vs Advertising Labeling regulations 21 CFR Part 201 http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/ cfCFR/CFRSearch.cfm?CFRPart=201 http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/ cfCFR/CFRSearch.cfm?CFRPart=201 Advertising regulations 21 CFR Part 202 http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/ cfCFR/CFRSearch.cfm?CFRPart=202 http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/ cfCFR/CFRSearch.cfm?CFRPart=202

5. FDA vs FTC FTC regulates advertising (cars, home mortgages, mops, etc.) FDA regulates labeling and advertising (drugs, medical devices, foods) Memorandum of Understanding - Ads FTC regulates ads for foods, OTC drugs, non-restricted devices, cosmetics, dietary supplements FDA regulates ads for prescription drugs and restricted medical devices

6. What is labeling? Section 201(m) of the FD&C Act states labeling "... means all labels and other written, printed, or graphic matter... accompanying such article." The regulations provide examples of labeling under 21 CFR 202.1(l)(2): "Brochures, booklets, mailing pieces, detailing pieces, file cards, bulletins, calendars, price lists, catalogs, house organs, letters, motion picture films, film strips, lantern slides, sound recordings, exhibits, literature, and reprints and similar pieces of printed, audio or visual matter descriptive of a drug and references published (for example, the Physician's Desk Reference) for use by medical practitioners, pharmacists, or nurses, containing drug information supplied by the manufacturer, packer, or distributor of the drug and which are disseminated by or on behalf of its manufacturer, packer, or distributor are hereby determined to be labeling as defined in section 201(m) of the FD&C Act."

7. What is prescription drug advertising? 21 CFR 202.1(l)(1) states that advertisements subject to Section 502(n) of the Food, Drug, and Cosmetic Act (FD&C Act) include advertisements published in journals, magazines, other periodicals, and newspapers; and broadcast through media such as radio, television, and telephone communications systems. This is not a comprehensive list of advertising media subject to regulation. For example, FDA also regulates advertising conducted by sales representatives, on computer programs, through fax machines, or on electronic bulletin boards.

8. What must a prescription drug advertisement include? Under section 502(n) of the FD&C Act, advertisements must include: the established name, the brand name (if any), the formula showing quantitatively each ingredient, and information in brief summary which discusses side effects, contraindications, and effectiveness. The brief summary is further discussed in 21 CFR 202.1(e)(1).

9. What is a reminder advertisement? 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.

10. Commonly asked question… Does FDA limit the amount of money that can be spent on reminder advertisements or reminder labeling 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, and not just the written information, but information that may be portrayed though graphics, design, or some other visual representation.

11. # of Final Promotional Pieces Submitted (2253s) 2004 - 2008

12. Consumer Promotion Submission Trends

13. # of Broadcast Ads Submitted 2003 - 2008

14. FDA’s New Medical Product Promotion Websites Two websites launched in September 2008 Provide information to public/industry on how FDA regulates promotion of medical products Medical Product Promotion website: http://www.fda.gov/oc/promotion/ http://www.fda.gov/oc/promotion/ Central location for information on medical product promotion

15. EthicAd website Located at: http://www.fda.gov/cder/ethicad/index.htm http://www.fda.gov/cder/ethicad/index.htm Designed primarily for consumers as a guide about DTC prescription drug advertising uses interactive example ads to illustrate different requirements for different types of ads (reminder, help-seeking, full product) includes questions consumers should ask when they see an Rx drug ad – consumers can print out for discussions with healthcare providers

16. EthicAd Provides questions for consumers, overview of ad requirements, glossary of terms, FAQs, sample ads, and background on FDA authority over advertising

19. FDAAA - Direct to consumer (DTC) Advertising Food and Drug Administration Amendments Act of 2007 (FDAAA) Fees for advisory review - $6.25 million annually 27 FTEs for voluntary review 31 companies committed to purchase a total of 151 TV ad review credits for first fiscal year of program; $41,390 for each TV ad submitted for advisory review Consolidated Appropriations Act, 2008, signed December 26, 2007 (Pub. L. No. 110-161), did not appropriate user fee funds for voluntary DTC review program As a result, FDA did not have authority to collect and spend user fees, and program could not legally commence Notice issued indicating the program would not be implemented: http://www.fda.gov/OHRMS/DOCKETS/98fr/E8-740.pdf

20. What now for DTC? TV ads will be reviewed in as timely a manner as resources permit Pre-review - authorized Civil money penalties Statement in DTC Ads : “You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088”

21. Adderall XR Warning Letter Video testimonial featuring Ty Pennington posted on youtube.com by Shire Development Inc (Shire) for Adderall XR Shire acknowledged its involvement in the development and dissemination of the video

22. Adderall XR Warning Letter Overstatement of Efficacy Ty claims “Now once I got on medication it’s just amazing the transformation I made. I – It literally changed my life, and gave me the confidence to achieve my goals.... But the medicines like Adderall XR, it’s truly a transformation.... It’s not easy to communicate with people, including your own family. So you become kind of alienated. You feel like you’re different, and you don’t really fit in..... Proper treatment has truly changed my life and made an amazing difference.

23. Adderall XR Warning Letter Omission of Risk Information Video presents numerous efficacy claims but entirely omits risk information Failure to Submit Under Form 2253

24. Yaz Warning Letter Two TV ads Broadening of Indication Premenstrual Dysphoric Disorder (PMDD) Misleadingly suggest that Yaz is appropriate for treating women with PMS Nowhere do the ads use the full phrase “premenstrual dysphoric disorder” Omit material limitation that “Yaz has not been evaluated for the treatment of premenstrual syndrome (PMS)” Acne Fails to adequately convey that Yaz is only indicated for the treatment of “moderate acne vulgaris”

25. Yaz Warning Letter Overstatement of Efficacy PMDD TV ad “Balloons” misleadingly suggests that treatment with Yaz will allow women to say “good- bye” to their symptoms, when such an elimination has not been demonstrated by substantial evidence or substantial clinical experience Acne Overwhelming impression conveyed by the TV ads is that treatment with Yaz results in clear, acne-free skin for those women suffering from acne when this has not been demonstrated by substantial evidence or substantial clinical experience

26. Avodart Untitled Letter TV ad entitled “Planetarium” Misleading Comparative Claims “So when my doctor said that my going and going could get worse because my prostate was growing I said ‘How can we shrink it?’” “He said ‘Avodart.’” “Avodart is different because over time it actually shrinks the prostate, so I go less often. Other medicines, they don’t treat the cause, because they don’t shrink the prostate.”

27. Avodart Untitled Letter Overstatement of Efficacy Graphic images and verbal statements overstate the efficacy of Avodart therapy with respect to the results one can expect with Avodart Visual of the planet shrinking in size represents a reduction in prostate volume that is much greater than the reduction actually achieved with Avodart therapy in clinical trials

28. Sponsored Internet Link Untitled Letters Issued 14 untitled letters to 14 different companies regarding sponsored links on internet search engines Letters covered 48 drugs 19 of the products carry Boxed Warnings Violations included: Broadening or inadequately disclosing the actual FDA-approved use of the drugs Overstating the drugs benefits Not providing any risk information Failing to use the drug’s established name

31. Good Reprint Practices Guidance: “Good reprint practices for the distribution of medical journal articles and medical or scientific reference publications on unapproved new uses of approved drugs and approved or cleared medical devices” Describes types of reprints/articles/reference publications, such as: Not false or misleading Journal article: e.g., peer reviewed, expert editorial board Reference: e.g., not written, edited, etc specifically for company, not edited or significantly influenced by company Describes manner in which to disseminate scientific and medical information, such as: Unabridged reprint or copy Not marked, highlighted, summarized, etc Accompanied by approved labeling Distributed separate from promotional material Statement that uses described have not been approved by FDA, other disclaimers

32. What is ClinicalTrials.gov? ClinicalTrials.gov is a publicly accessible clinical trial registry and results databank. It provides regularly updated information about federally and privately supported clinical trials. Each record provided in ClinicalTrials.gov lists the following: Disease or condition and experimental treatments studied Title, description, and design of study Requirements for participation Locations where the study is available Contact information Links to relevant information at other health Web sites, such MedlinePlus and PubMed Pharmacy Today (March 2009): ClinicalTrials.gov: A resource for pharmacists

35. FDAAA – Clinicaltrials.gov expansion Expansion of registry Goes beyond serious and life-threatening trials All beyond Phase I- drug and device Computer links to existing information -- including FDA information such as advisory committee summary documents, medical reviews, public health advisories, action package, summary of safety and effectiveness data Results Databases Basic: 9/29/2008 Expanded: 9/28/2010

40. Drug Safety Communications FDA’s enhanced efforts to communicate drug safety information to patients and health professionals Quarterly reports of potential drug safety issues Potential signals of serious risks/new safety information identified using the AERS database during the quarter…further evaluation by FDA will be done MedWatch Listserv www.fda.gov/medwatch/index.html DailyMed Current Labeling An FDA/National Library of Medicine collaboration CDER Drug Safety Newsletter Quarterly web-based notification of selected new drug safety information www.fda.gov/cder.dsn/default.htm CDER Drug Safety podcasts Episodically-issued podcasts associated with Public Health Advisories for drugs http://www.fda.gov/cder/drug/podcast/default.htm Patient Safety News Monthly video broadcast on featured drug and device safety issues www.accessdata.fda.gov/scripts/cdrh.cfdocs/psn/index.cfm CDER mailing lists www.fda.gov/cder/cdernew/listserv.html

41. Summary & Questions Ilisa B.G. Bernstein, Pharm.D., J.D. ilisa.bernstein@fda.hhs.gov