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

Scope of FDA Regulation Labeling Rx Advertising Other Promotional Vehicles –Sales Presentations –Educational/marketing events

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

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

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.

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

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

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

Direct-to-Consumer Current FDA initiative Brief Summary Broadcast Ads –Major Statement –Adequate Provision

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

Investigational Drugs 21 C.F.R. § 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

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)

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

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

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

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

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

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)

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