Four out of five doctors say that if they were stranded on a deserted island with no lawyers, they wouldn’t need any asp

1. Four out of five doctors say that if they were stranded on a deserted island with no lawyers, they wouldn’t need any aspirin. American Medical Association

2. DeviceLabeling and Promotion presented byBradley Merrill Thompson Epstein Becker & Green, P.C. February 27, 2009

3. Topics Part One Regulatory Requirements Part Two Claim Substantiation Part Three Off-Label Promotion Part Four Marketing in a Regulated Environment Part Five Case Studies I feel like Zsa Zsa Gabor’s fifth husband. I know what I'm supposed to do but I don't know if I can make it interesting. Al Gore

4. Part One: Regulatory Requirements Topics • Definitions • Fundamental prohibition • Special labeling rules • Risks in interactions with physicians Actual Trial Question What happened then? He told me, he says, “I have to kill you because you can identify me.” Did he kill you?

5. It’s good to know the basics politicalhumor.about.com

6. Definitions • “Label" is a: display of written, printed, or graphic matter upon the immediate container of any article.... • “Labeling" is: all labels and other written, printed, or graphic matter (1) upon any article or any of its containers or wrappers, or (2) accompanying such article.

7. Definitions • “Accompanying": • Is interpreted liberally to mean more than physical association with the product • Extends to posters, tags, pamphlets, circulars, booklets, brochures, instruction books, direction sheets, fillers, etc., depending how they are used • Includes labeling that is brought together with the device after shipment or delivery for shipment in interstate commerce. • But what of an oral sales pitch?

8. Definitions Advertising • Not defined in the FFDCA • FDA likes to treat advertising as labeling • According to an appellate court decision: "Most, if not all advertising, is labeling.… Congress did not, and we cannot, exclude from the definition printed matter which constitutes advertising.” • But consider radio and TV ads • Where do magazine ads fit • FTC has jurisdiction over device advertising other than for restricted devices

9. Fundamental Prohibition • The term misbrandedmeans: • “Falseor misleadingin any particular.” • False generally is understood to mean a statement that in any material respect is untrue. • Misleading is less clear • Twin goals of— • Safety and effectiveness • Preventing economic fraud

10. Truth in Advertising Funky.co.uk

11. More Truths

12. Fundamental Prohibition • Examples of false labeling include: • Incorrect, inadequate or incomplete identification • Unsubstantiated claims of therapeutic value • Substitution of parts or material • Inaccuracies concerning condition, state, treatment, size, shape or style

13. Good Accuracy 4.bp.blogspot.com

14. Mixed Disclosure www.txrollergirls.com

15. Fundamental Prohibition • Examples of misleading labeling include: • Ambiguity, half-truths, and trade puffery • Expressions of opinion or subjective statements • Failure to reveal material facts, consequences that may result from use, or the existence of difference of opinion

16. Adequate Disclosure? Photoshoptalent.com

17. Fundamental Prohibition • Examples of other objectionable labeling practices include • Deceptive pictorial matter • Misleading testimonials • Misleading list of parts or components • Use of brand or trade names instead of "established names" Often the surest way to convey misinformation is to tell the strict truth. Mark Twain

18. Misleading testimonial? A6.vox.com

19. Good Use of Brand Name

20. Could be deceptive Img.ffffound.com

21. What else is misbranded? • FDA specifically requires certain information, prominently displayed (unless exempt): • Established name of the product • Name and place of business of themanufacturer, packer, or distributor • Net quantity of contents • Adequate directions for use andadequate warnings

22. Make sure materials are clear www.gdarguad.net

23. Exemptions from Adequate Directions for Use • Prescription devices • Commonly-known directions • IVDs • Products intended for further processing • Teaching, law enforcement and research

24. FTC Regulation of Advertising • FTC has jurisdiction over advertising for a non-restricted device • FTC applies three requirements • Adequate substantiation • No deception, from the standpoint of the reasonable consumer • Fairness • Agency influenced by lawyers who focus on consumers and how they are affected

25. Lanham Act • Action against a competitor in federal court • Liability arises from deceptive statements about either the competitor’s or the company’s own product alleged to harm the other party, including: • False or misleading claims • Unsubstantiated comparative claims • Overstatements of efficacy • Minimization of risks • Damages & injunctive relief are available

26. State Regulation of Advertising • State Food Drug & Cosmetic Acts • State consumer protection laws • Enforcement by state attorneys general • Consumer class actions Politics gives guys so much power that they tend to behave badly around women. And I hope I never get into that. Bill Clinton

27. Risks in Interactions with Physicians Applicable law • Federal Anti-kickback statute • Fraud and Abuse provisions of the Social Security Act (Medicare/Medicaid statute) • Federal False Claims Act • State Anti-kickback statutes • State False Claims Acts • State statutes requiring disclosure of gifts to prescribers

28. Risks in Interactions with Physicians Government enforcement risks arise in the context of: • Business courtesies • Ensure sales personnel follow applicable guidance with respect to gifts, meals and entertainment • Consulting arrangements • Consulting arrangements must be for necessary services pursuant to written agreements in compliance with regulatory requirements • Research grants • Grants should be administered outside marketing function, based on objective criteria • Educational activities & meetings • Sponsored meetings must take place in locations conducive to educational activities, without providing entertainment and with only modest meals and accommodations

29. Part Two: Claim Substantiation Topics Generally Comparative claims Establishment claims The pure and simple truth is rarely pure and never simple.Oscar Wilde

30. Claim Substantiation Generally • Refers to the evidence needed to support a claim regarding some feature or performance of the device • Must support both express and implied claims • In labeling, revolves around the FDCA “false and misleading” language • In advertising, revolves around the FTC standard requiring a reasonable basis in objective evidence before the claim is made • Unlike with drugs, there is no explicit FDA guidance yet on device claim substantiation

31. FTC Factors for Adequate Substantiation • Type of product • Type of claim • Benefits of a truthful claim • Cost/feasibility of developing substantiation for the claim • Consequences of a false claim • Amount of substantiation that experts in the field believe is reasonable

32. Comparative claims • These compare the device to another device • FDA considers them inherently misleading • Requires that such claims be supported by sound scientific data, usually a rigorous study that directly compares the devices • FTC does not have that same predisposition, instead favoring useful comparisons • But likewise requires rigorous scientific evidence, again a study or studies comparing the devices

33. Establishment claims • These are claims that declare or even suggest that a device’s superiority has been scientifically proven • Both FDA and FTC require the company to have at least the level of evidence stated or implied in the claim • There is also a baseline of support required • Studies must be able to withstand criticism

34. Part Three: Off-Label Promotion • Off-Label Use Rules • Basic Intended Use Framework • Evolution of the Legal Landscape • Promotion Dos & Don’ts • First Amendment Issues Winter related injuries occur more often in the winter.-newswoman for WHIZ-TV, Zanesville Ohio

35. Basic Intended Use Framework Under 21 CFR 801.4, the words “intended uses” … refer to the objective intent of the persons legally responsible for the labeling of devices. The intent is determined by such persons' expressions or may be shown by the circumstances surrounding the distribution of the article. This objective intent may, for example, be shown by labeling claims, advertising matter, or oral or written statements by such persons or their representatives. It may be shown by the circumstances that the article is, with the knowledge of such persons or their representatives, offered and used for a purpose for which it is neither labeled nor advertised. …

36. Off-Label Use Rules: Basic Framework • The uses promoted are “intended uses” under 21 CFR 801.4 • If an intended use is for other than the approved indication, the lack of approval and inadequate labeling make device “adulterated” and “misbranded” If promoted off-label, a device may be deemed “misbranded” or “adulterated”

37. Evolution of the Legal Landscape Where FDA was: Strict regulation of off-label promotion • FDA Guidances • Guidance on Dissemination of Reprints and Reference Texts (1996) • Guidance on Industry Supported Scientific and Educational Activities (1997)

38. Evolution of the Legal Landscape Then FDAMA Section 401 (1997) • Sets forth process for disseminating off-label information • Requires disclosure statements & labeling • Requires later filing for approval of any unapproved uses in the materials • Sets forth audience restrictions • Limited to dissemination of certain referencejournals • Now sunset Gofethiye.com

39. Evolution of the Legal Landscape The Next Change • FDA’s authority to regulate off-label promotion has been limited by the courts • Washington Legal Foundation • Western States Medical Center • More on those later • Result: FDA cannot infringe on the right of medical device companies to promote their products – on-label or off-label – if other, less restrictive measures can achieve FDA's goals

40. Evolution of the Legal Landscape What the Law is NOW • FDCA sections on misbranding are still in effect • FDAMA 401 provisions on dissemination of off-label materials and regulations have sunset • CME guidance is still in effect • New Guidance on journal reprints • FDA cannot infringe on promotion of products if it has other options

41. First Amendment • FDA’s authority to regulate off-label promotion has been limited by the courts – any such regulation must be narrowly tailored to achieve FDA's purpose • Cases: • Washington Legal Foundation v. Henney (2000) • Thompson v. Western States Medical Center (2002)

42. Washington Legal Foundation • WLF brought action challenging 1996/1997 Guidances (and later, FDAMA) as unconstitutional under the First Amendment • WLF won at trial • On appeal, when FDA asserted they were not mandatory, but created only safe harbors, the court held the matter was not ripe for determination—a technicality

43. Washington Legal Foundation • Trial court suggested restrictions of its own, which many manufacturers have adopted. • Articles from bona fide peer-reviewed journals or text books published by a bona fide independent publisher • Product must be cleared or approved for at least one indication • False and misleading materials still open to FDA enforcement • Must disclose off-label use • Must disclose any relationship between the company and product or authors

44. Western States • Background: FDAMA exempted "compounded drugs" (mixed by pharmacist) if, among other things: • Drug is compounded by licensed pharmacist • Providers don't advertise or promote compounding of a particular drug, drug class or drug type • Challenge: • Compounding provision challenged by group of pharmacies arguing provisions prohibiting advertising violated First Amendment

45. Western States • U.S. Supreme Court held FDAMA compounding provision unconstitutional • Lesson learned: • Government must use the least restrictive means possible to achieve its objectives • If government can achieve its purpose without restricting speech, or by restricting less speech, it must do so

46. Impact of the Litigation • FDA cannot infringe on the right of medical device companies to promote their products if other, less restrictive measures can achieve FDA's objectives, such as: • Disclaimers and warning labels • Disclosures • Limitations on non-speech related activity • Narrowing of speech restrictions • FDA is reassessing its own authority • On May 16, 2002, FDA requested comments on its authority to regulate communications; More than 730 comments received

47. SEC Disclosure Requirements • SEC’s requirement that companies disclose material information to the investment community, including both positive and negative results of clinical trials, is often inconsistent with FDA’s limitations on disclosure • Clash of pro-speech policy with FDA’s speech restrictions • First Amendment typically does not permit regulation of speech based on audience • SEC has brought enforcement actions against companies for failure to disclose important information about products in clinical trials

48. Conclusions • Basic principle: Truthful speech should be allowed • Many argue that “truthful” should be judged in the eye of the audience • Doctors are sophisticated; they can be told the truth • Patients should be protected • Begs the question, what level of substantiation is required to establish the truthfulness of a statement? • But is handing a doctor a peer-reviewed article untruthful? Does it matter who hands it? • FDA needs to protect the integrity of its clearance/approval process

49. Part Four: Marketing in a Regulated Environment • The Stages of Promotion • General Risk Areas • Good Reprint Practices • Unsolicited Requests • Contracts for future generations • Investor Communications • Websites • Trade Shows • Scientific Meetings • Trends in Enforcement • Good Promotional Practices The voters have spoken—the bastards. Richard M. Nixon

50. A lot of the rules are obvious www.okaponds.com