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FDA Regulation of Promotion & Advertising Part 6B: First Amendment, Off-Label and False Claims


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November 10, 2017 presentation to the ComplianceOnline course on Ensuring Compliance with FDA Regulation of Promotion & Advertising of Drugs and Medical Devices, in Boston.

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FDA Regulation of Promotion & Advertising Part 6B: First Amendment, Off-Label and False Claims

  1. 1. ©2010 Copyright © 2015 ComplianceOnline This training session is sponsored by 1 FDA Regulation of Promotion & Advertising Part 6B: First Amendment, Off-Label and False Claims ComplianceOnline Seminar November 6-7, 2014 • Michael A. Swit, Esq.
  2. 2. ©2015 Copyright First Amendment  Adopted December 15, 1791 – Congress shall make no law respecting an establishment of religion, or prohibiting the free exercise thereof; or abridging the freedom of speech, or of the press; or the right of the people peaceably to assemble, and to petition the Government for a redress of grievances.  “Commercial Speech” – does not get “full” 1st Am. protection – Advertising – clearly is commercial speech 2
  3. 3. ©2015 Copyright  Alfred Caronia – – Sales rep for Orphan Medical (now Jazz Pharm.) – convicted of conspiracy to introduce a misbranded drug into commerce – for an unapproved use (off-label) – Appealed • Caronia -- contended that he was prosecuted for his speech • FDA – his speech was not the issue, it was just used as evidence of his intent … to misbrand the drug Caronia and Off-Label Promotion 3
  4. 4. ©2015 Copyright  The Facts – Xyrem – powerful central nervous system depressant; approved (GHB – “date rape” drug) – approved (1) to treat narcolepsy patients who experience cataplexy and (2) to treat narcolepsy patients with excessive daytime sleepiness (EDS); severe side effects • Black box warning – elderly and pediatric patients under 16 • Limited distribution – single pharmacy in Missouri – Caronia – started a speaker program for Xyrem • Caronia – not allowed to answer questions on off-label use; had to send info into company • Physician Speakers – could answer off-label questions Caronia and Off-Label Promotion … 4
  5. 5. ©2015 Copyright  The Facts … – “The Conspiracy” • Caronia taped – 10/26 – Dr. Charno – promoted Xyrem for uses such as fibromyalgia, insomnia, “muscle disorders and chronic pain” – 11/2/05 – Dr. Charno and Gleason • Caronia and Peter Gleason – pushed Xyrem for children under 16 – Pled guilty originally; moved to have plea dismissed, claiming that the application of the misbranding theory essentially violated his 1st Am rights to speech Caronia and Off-Label Promotion … 5
  6. 6. ©2015 Copyright  The “Misbranding Theory” – Misbranding theory of off-label promotion – that there are not adequate directions for use for the off-label use, but that the off-label use has become an “intended use” as defined in FDA regulations and directions for use, under 21 CFR 201.5, must cover all “intended uses” (even off-label) • 21 CFR 201.128 – objective intent of person -- allows “intended use” to be shown by oral or written statement and … “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.” • Government – not possible to write adequate directions for use for an off-label use Caronia and Off-Label Promotion … 6
  7. 7. ©2015 Copyright Caronia and Off-Label Promotion …  Decision … – First, 2nd Circuit concluded that the trial record made clear that the govt prosecuted Caronia for the speech – the off-label promotion – On appeal, Caronia argued that the misbranding provisions, by prohibiting off-label promotion, impinge the 1st Am. – Court – took a slightly narrower approach – • concluded that he was prosecuted for “mere off-label promotion” (speech) and that was improper – no proof offered at trial of deficient labeling, for example • also concluded that the misbranding provisions don’t criminalize speech per se 7
  8. 8. ©2015 Copyright Caronia and Off-Label Promotion …  Court – 1st Am. violated in several ways – Sorrell case – Heightened scrutiny • Content based –distinguishes between “favored” and “unfavored” speech based on the ideas expressed – favored = approved use – unfavored = unapproved use • Speaker based – distinguished between types of speakers – docs – could talk about off-label use – drug companies – could NOT – Central Hudson – Intermediate Scrutiny • ….continued … 8
  9. 9. ©2015 Copyright “Central Hudson” 4-Prong Test  1 -- Is the expression protected by the First Amendment and not misleading and related to lawful activity? – Yes, speech; related to lawful activity (off-label use) and not misleading (if true)  2 -- Is the asserted government interest substantial? – Yes, drug safety and public health  3 -- Does the regulation directly advance the governmental interest asserted? – No, because off-label use is acceptable and this ban on promotion actually inhibits that use by docs 9
  10. 10. ©2015 Copyright  3 -- Does the regulation directly advance the governmental interest asserted? … • besides, FDA actually allows distribution of off-label info under draft Good Reprint Guidance  4 – Is the restriction narrowly drawn to further gov’t interest – No, there are other ways to address that FDA and government are not pursuing. For example, the law actually bars off-label use of HGH – Section 303(f) of Act – Regulating speech should be last resort “Central Hudson” 4-Prong Test 10
  11. 11. ©2015 Copyright Future after Caronia?  Wild West? Snake Oil? – 2nd Circuit -- is just NY, VT, & CT – Government – will probably focus on: • failure to provide adequate directions for use, because the product is being promoted for an off-label use, in future actions • unapproved drug actions – Off-label promotion – must essentially be in writing – 21 CFR 801.4 – device maker required to provide info on labeling if it learns that its product is being used off-label • See Dexcom Warning Letter; May 2010, where FDA asked for labeling changes on off-label uses (pediatrics; incision location) 11
  12. 12. ©2015 Copyright  Very unique set of facts – Drug: Vascepa (icosapent ethyl) – “fish oil” • Approved originally for to reduce triglyceride levels in adults with severe – or “very high” -- hypertriglyceridemia (≥ 500 mg/dl) – 2012 • SPA – new indication – “persistently high” triglycerides (≥ 200 to ≤500) – ANCHOR trial, to be followed by the REDUCE-IT trial (which would study Vascepa impact on reducing CV events) • ANCHOR study – statistically significant results on primary endpoint • sNDA in 2013 based on ANCHOR trial • FDA – convened AdCom – called into question whether ANCHOR endpoint of reducing triglycerides = lowering of CV events (which the REDUCE-IT was supposed to address) • FDA – complete response letter, which also included a warning not to publicize the ANCHOR study. • Other factor – Fish Oil supplements can make a qualified health claim about benefits of fish oil on CV events Amarin 12
  13. 13. ©2015 Copyright  Lawsuit – Preemptive strike by Amarin – Court decision on preliminary injunction: • “Real and imminent fear” of prosecution present due to threat in Complete Response Letter of misbranding if Amarin publicized • Applied Caronia (same circuit) • True -- what Amarin was saying was true as was clear by an extensive record • Not misleading – Amarin offered to distribute the info with clear disclaimers that: – No approval for the persistently high indication – Amarin had proposed a qualified cardioprotective claim which was very similar to the one FDA allows for Fish Oil supplements • Did note that Amarin had duty to ensure that changes in science did not alter its conclusions and disclosures – Settlement – talks underway; FDA avoiding precedent setting Amarin 13
  14. 14. ©2015 Copyright False Claims Act and Off-Label Promotion 14
  15. 15. ©2015 Copyright False Claims Act  Enacted during Civil War; creates a bounty for anyone who blows whistle on unscrupulous government contractors – Qui Tam – actions filed under seal; government can later join – Recovery – percentage (varies) – can go to the “relator” (the whistleblower)  Late 1990’s – began to emerge in FDA-regulated violations – Neurontin – one of the first big ones -- $430,000,000 • (whistleblower got about $25 mil.)
  16. 16. ©2015 Copyright  Orphan Medical – Xyrem -- $20 million  BMS/Otsuka – Abilify – $50 million – Pediatric and to treat dementia (approved for MDD, PD, etc.)  Cephalon -- $375 million for three drugs – Actiq – pain in non-cancer patients (approved in cancer) – Gabitril – anxiety, insomnia, pain (approved for partial seizures) – Provigil – fatique and other “stimulant” uses(approved for narcolepsy)  Lilly – Zyprexa -- $1.4 Billion – anti-psychotic marketed for numerous off-label uses False Claims Act Settlements 16
  17. 17. ©2015 Copyright  Pfizer I – Bextra, Geodon, Lyrica -- $2.3 billion – six whistleblowers shared $102 million  Allergan – Botox -- $600 million – chronic migraines (later approved for use)  Abbott – Depakote -- $1.6 billion  GSK – Paxil, etc. -- $3 billion False Claims Act Settlements 17
  18. 18. ©2015 Copyright FCA – What's’ Involved  Civil monetary penalties – range from $5,500 to $11G per violation; up to 3 times amount of damage sustained by government  Focus of off-label liability – Federal healthcare programs -- not responsible for paying for unapproved uses  Filed under seal – although you likely know if you’re under investigation  Whistleblower – protected from retaliation 18
  19. 19. ©2015 Copyright End of Part 6 – First Amendment, Off-Label and False Claims
  20. 20. ©2015 Copyright Questions?  Call or e-mail: Michael A. Swit, Esq. LAW OFFICES OF MICHAEL A. SWIT San Diego, California m: 760-815-4762 e: web:  Follow me on: – LinkedIn: – Twitter:
  21. 21. ©2015 Copyright About Your Speaker Michael A. Swit, Esq., has been addressing critical FDA legal and regulatory issues since 1984. Before returning to his private law practice in late 2017, he served for 3 years at Illumina, Inc. as Senior Director, Legal, Regulatory. Prior to that, Swit was a special counsel at the global law firm of Duane Morris LLP in its San Diego office. Before joining Duane Morris in March 2012, Swit served for seven years as a vice president at The Weinberg Group Inc., a preeminent scientific and regulatory consulting firm in the Life Sciences. His expertise includes product development, compliance and enforcement, recalls and crisis management, submissions and related traditional FDA regulatory activities, labeling and advertising, and clinical research efforts for all types of life sciences companies, with a particular emphasis on drugs, biologics and therapeutic biotech products. His FDA legal and regulatory work also has included tenures in private practice with McKenna & Cuneo and Heller Ehrman, and as vice president, general counsel and secretary of Par Pharmaceutical, a top public generic and specialty drug firm. He also was, from 1994 to 1998, CEO of, a premier publisher of regulatory newsletters and other specialty information products for FDA-regulated firms. He has taught and written on many topics relating to FDA regulation and associated commercial activities and is a past member of the Food & Drug Law Journal Editorial Board. He earned his A.B., magna cum laude, with high honors in history, at Bowdoin College, and his law degree at Emory University.