FDA Regulation of the Dissemination of Medical Device Information Daniel A. Kracov Medical Device Congress Marc

1. FDA Regulation of the Dissemination of Medical Device Information Daniel A. KracovMedical Device Congress March 27, 2008

2. Key Terms (cont’d) • Labels: Immediate container/package • Labeling: Accompanying materials / textual relationship • Advertising: Everything else – potential overlap • Intended Use:Objective intent of the persons legally responsible for the device. • Statements, written or oral, labeling, advertising, website • Under the Federal Food, Drug, and Cosmetic Act (FFDCA), a medical device may be sold only for its cleared/approved intended uses.

3. Key Terms (cont’d) • Misbranding:Section 502 of the FFDCA • false or misleading labeling • failure to provide adequate directions for use in labeling • failure to provide adequate warnings in labeling • failure to include required labeling information • failure to include relevant side effects / contraindications / warnings / precautions in advertising (restricted devices)

4. Key Terms(cont’d) • Adulteration: Section 501(f) of the FFDCA • No PMA for Class III device (as required by § 515) • Prohibited Acts: • Distribution of adulterated or misbranded medical device. Section 301(a) of the FFDCA • Failure to follow 510(k) requirements. Section 301(p) of the FFDCA • Promotion of investigational devices • Commercialization prohibited under 21 C.F.R. § 812.7 • May not represent investigational device as safe and effective

5. Key Terms • Off-Label Use: Physician uses a medical device for a clinical purpose not included on the product’s official labeling • Off-Label Promotion: A device manufacturer makes marketing claims for the product regarding a clinical use not included in the labeling • May make the device an unapproved device, and may otherwise result in the misbranding and adulteration of the device • Off-Label Education: A device manufacturer disseminates medical literature (or underwrites continuing medical education programs) that discuss a clinical use not included in the labeling • “Scientific Exchange”

6. Promotion for Off-Label Uses • Adult device marketed for use in pediatric settings • Device marketed for diagnosis rather than aid in screening/detection • Diagnostic marketed for broader diagnosis than labeled • Biliary stent marketed for vascular surgery • Device not cleared for ambulatory patients marketed for ambulatory use

7. What are the risks? • Liability under the Federal Food, Drug, and Cosmetic Act • Liability under the False Claims Act • State law liability • Attorneys General • Liability to consumers • Product liability • Loss of preemption and other defenses • Deceptive/unfair trade practices / fraud • RICO • Competitor liability • Lanham Act • Liability to shareholders and SEC • Criminal liability due to wire fraud, obstruction, etc. • Limitations on insurance coverage

8. How far beyond the “safe harbors” is unsafe? • Manufacturer compliance policies/risk profile vary. • Major risks • Need to look at the overall pattern of activities and compliance system

9. Areas of Risk • Business and strategic planning documents • ROI analyses for off-label activities • Market research • Publication plans • Product development records showing decisions not to seek FDA approval/clearance • Tracking of off-label uses

10. Areas of Risk (cont’d) • Advisory Boards • Consultants • Reimbursement assistance • Website links and chat rooms

11. Areas of Risk (cont’d) • Grant activities • Involvement of marketing and sales • Continuing Medical Education • “Wholly owned” grantees • Development of treatment guidelines and algorithms • Grants to state agencies and health care entities • Comparative claims where the competitor has broader labeling • Success stories and testimonials stating off-label uses • Briefings for analysts

12. Areas of Risk: Sales Force • Training materials and sales meetings • Trade show statements • “Homemade” materials • “Hands-on training” activities

13. Areas of Risk: Sales Force (cont’d) • Call notes and e-mails • Detailing to “off-label” medical specialties • Sampling patterns • Compensation systems

14. “Safe Harbors” for Conveying Off-Label Information • Unsolicited Requests • FDAMA, Section 557 of the FFDCA • Must be bona fide, not cued • Responsive to scope of the request • Objective, balanced – a medical communication • Documentation of requests • Patterns suggesting solicitation • Role of Medical Affairs • Scripting of transitions to Medical Affairs • Pre-packaged response materials

15. “Safe Harbors” (cont’d) • Continuing Medical Education • 1997 FDA Guidance (62 Fed. Reg. 64074 (Dec. 3, 1997) • Content relating to unapproved products or off-label • Agreement with accredited provider • Independent, nonpromotional, educational • No company control over content/presenters (suggestions may be acceptable) • Disclose funding, company relationships, unapproved products • Balance in presentation, opportunity for discussion • No sales/marketing involvement/exhibits in room • Program materials disseminated by CME provider only • Compliance record

16. “Safe Harbors” (cont’d) • Dissemination of Off-Label Journal Articles and Other Off-Label Materials • Washington Legal Foundation Case • Applicability of First Amendment to medical device/pharmaceutical industry commercial speech • Controversy continued for many years; a series of decisions • Ultimately inconclusive • … but see U.S. v. Caputo • Abtox Plazlyte hospital sterilizer • Unsuccessful First Amendment defense to off-label marketing.

17. “Safe Harbors” (cont’d) • FDAMA Section 401 • Sunsetted • Extremely narrow and burdensome • Dissemination of reprints of journal articles and reference texts discussing unapproved new uses • Not false or misleading, or a significant risk to public health • Target audience limited to health care practitioners, pharmacy benefit managers, health insurance, group health plans, federal/state agencies

18. “Safe Harbors” (cont’d) • FDAMA Section 401(cont’d) • presubmission of publication to FDA (60 days) • presubmission of all clinical trial information • prominent disclosure statement; bibliography • additional information; FDA objective statement • records and biannual report to FDA of all dissemination and recipients • submission of PMA supplement or 510(k) prior to dissemination, or certification that supplement will be submitted (6 mos./36 mos.)

19. FDA Draft Guidance on Reprints • 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 (February 2008) • http://www.fda.gov/OHRMS/DOCKETS/98fr/FDA-2008-D-0053-gdl.pdf • Objection by House OGR Committee Chairman Waxman • http://oversight.house.gov/documents/20071130102744.pdf

20. Eli Lilly / Evista® (2005) • Alleged illegal promotion of an osteoporosis drug for off-label uses (prevention of breast cancer and cardiovascular disease) • Traditional FDA “intended use” theory • Prompted questions by sales force • Training of sales force in off-label uses • “Best practices” videotape • Consultant meetings • Tracking of prescriptions • Consent Decree • $24 million in equitable disgorgement • Criminal fine of $6 million • Forfeiture of $6 million • Corporate Integrity Agreement in an FDA Consent Decree • No exclusion

21. Questions?Daniel A. KracovArnold & Porter LLP555 Twelfth Street, N.WWashington, D.C. 20004(202) 942-5120 phone(202) 942-5999 facsimileDaniel.Kracov@aporter.com