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

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.

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)

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

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”

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

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

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

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

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

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

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

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

“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

“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

“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.

“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

“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.)

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

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

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. 20004 (202) 942-5120 phone (202) 942-5999 facsimile Daniel.Kracov@aporter.com