1. www.diahome.org Promotion of Prescription Drugs and Biologics Thomas O. Henteleff Kleinfeld, Kaplan and Becker LLP Company logo here

2. www.diahome.org Scope of FDA Regulation Labeling Rx Advertising Other Promotional Vehicles –Sales Presentations –Educational/marketing events

3. www.diahome.org Jurisdiction Rx Drugs –Review Division –Division of Drug Marketing, Advertising and Communications (Thomas W. Abrams) Biologics –Review Division –Advertising & Promotional Labeling Branch (Maryann Gallagher)

4. www.diahome.org Jurisdiction (cont.) Over-The-Counter Drugs –Advertising - Federal Trade Commission –Labeling - FDA

5. www.diahome.org Labeling vs. Advertising Labeling – written, printed, or graphic matter “accompanying” the drug –No physical connection required; textual relationship is key (e.g., website) –Defined by regulation to include brochures, booklets, detail pieces, catalogs, price lists, bulletins, etc (21 C.F.R. § 202.1(l)(2)) Advertising – generally paid media –Journals, magazines, TV, radio, etc.

6. www.diahome.org General FDA Requirements Not false or misleading –Affirmative (mis)statements & failure to reveal material facts Consistent with approved package insert (i.e., not “off-label”) Adequately supported by scientific evidence Fair Balance

7. www.diahome.org Submissions to FDA New Drugs/Biologics –21 C.F.R. §§ 314.81(b)(3), 601.12(f)(4) –Labeling & advertising: at initial dissemination or publication Accelerated Approval (§§ 314.550, 601.45) –Initial (for use during 1 st 120 days) labeling & advertising must be submitted before approval –Thereafter, 30 days prior to first use

8. www.diahome.org Types of Ads Preapproval –Coming Soon Ads –Institutional Ads Post-approval –Full Product Ads –Reminder Ads (21 C.F.R. § 202.1(e)(2)(i)) –Comparative Ads Help Seeking/Disease Awareness

9. www.diahome.org Direct-to-Consumer Current FDA initiative Brief Summary Broadcast Ads –Major Statement –Adequate Provision

10. www.diahome.org Comparative Claims Efficacy, safety, or cost comparisons Must relate to approved conditions of use Head-to-head data generally required in support Comparison of information in Package Inserts is not adequate support

11. www.diahome.org Investigational Drugs 21 C.F.R. § 312.7 Cannot promote or represent as safe or effective Cannot commercially distribute or test market Cannot commercialize by charging higher price than necessary to recover costs

12. www.diahome.org Off-Label Information Dissemination of mfr generated off-label info is strictly prohibited Limited ability to disseminated materials generated by third parties: –Unsolicited Requests –FDA Modernization Act of 1997 (FDAMA) –Washington Legal Foundation Case (WLF)

13. www.diahome.org Unsolicited Requests FDA policy/FDAMA – will not object to responses to unsolicited requests  Truly unsolicited – no prompting  Document the request  Monitor to detect prompting  Medical Affairs, rather than Marketing  Provide objective, balanced information

14. www.diahome.org FDAMA Section 401 Safe harbor to disseminate info about off- label uses of approved drugs in limited circumstances (21 C.F.R. Part 99) Detailed, burdensome requirements –Authorized information –Authorized audience/recipients –Prior notice to FDA/sNDA filing –Mandatory disclosures

15. www.diahome.org WLF Case – 1 st Amendment 1st Amendment right to exchange of truthful scientific information relating to off-label uses Court’s injunction was overturned as moot, but decision was procedural and the District Court analysis is still persuasive Very circumscribed dissemination of information pertaining to off-label uses may be protected by the 1 st Amendment

16. www.diahome.org WLF (cont.) Unaltered bona fide peer-reviewed journal article or reference textbook Only to healthcare professionals Product must be approved Identify mfr’s interest in product Disclose that use is not approved Avoid dissemination as a launching pad for discussion of off-label information

17. www.diahome.org Continuing Medical Education Industry-supported CME is regulated as promotion if not independent of mfr’s substantive influence 1997 FDA Guidance identifies criteria to evaluate independence Primary issue: discussion of off-label information

18. www.diahome.org FDA Enforcement Untitled Letter Warning Letter –Cease conduct; possible remedial action Adverse Publicity Injunction or consent decree –Kabi Pharmacia (1993) –Syntex (1991) –Eli Lilly (2005); Serono (2005); Warner-Lambert (2004); Tap (2001)

19. www.diahome.org Eli Lilly (12/2005) Off-label promotion of Evista Company pled guilty to criminal count of violating FDCA by misbranding Evista Consent decree of permanent injunction –Detailed compliance requirements Criminal fines and disgorgement total $36 million