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

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© 2015 ComplianceOnline
This training session is sponsored by
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FDA Regulation of Promotion & Advertising
Part 6B: First Amendment, Off-Label
and False Claims
ComplianceOnline Seminar
November 6-7, 2014
• Michael A. Swit, Esq.

www.complianceonline.com
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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
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 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
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 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 …
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 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
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 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
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 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
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 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 …
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“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
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 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
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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)
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 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
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 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
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False Claims Act and Off-Label Promotion
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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.)

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 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
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 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
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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
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Questions?
 Call or e-mail:
Michael A. Swit, Esq.
LAW OFFICES OF MICHAEL A. SWIT
San Diego, California
m: 760-815-4762
e: mswit@fdacounsel.com
web: www.fdacounsel.com
 Follow me on:
– LinkedIn: http://www.linkedin.com/in/michaelswit
– Twitter: https://twitter.com/FDACounsel

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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 FDANews.com, 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.

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