1. FDA Regulation of the Dissemination of Medical Device Information
FDA Regulation of the Dissemination of Medical Device Information Daniel A. Kracov Medical 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. Adulteration: Section 501(f) of the FFDCA Prohibited Acts:
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 s
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 (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)
Objection by House OGR Committee Chairman Waxman

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. Kracov Arnold & Porter LLP 555 Twelfth Street, N
Questions? Daniel A. Kracov Arnold & Porter LLP 555 Twelfth Street, N.W Washington, D.C (202) phone (202) facsimile