United States: Pharmaceutical Manufacturer's Preemptive Suit Secures Preliminary First Amendment Protection For Script To Promote Off-Label Use

On August 7, 2015, the U.S. District Court for the Southern District of New York invoked the First Amendment, granting Amarin Pharma, Inc. (Amarin) preliminary protection against federal criminal prosecution for misbranding and allowing Amarin to promote its drug, Vascepa, for off-label use through certain truthful, non-misleading speech.1 In so ruling, Judge Engelmayer applied the Second Circuit’s widely cited precedent in Caronia, which overturned a conviction under the same statutory provision.2 The extension of the much-scrutinized Caronia rule to a novel procedural posture raises important considerations for compliance officers and other staff in the pharmaceutical industry.

Factual Background

In 2012, Amarin obtained FDA approval for Vascepa to treat adults with “very high” triglycerides (defined as over 500 mg/dL of blood). Very high triglycerides are associated with increased risk of cardiovascular disease, so drugs that reduce triglycerides were expected to reduce the risk of cardiovascular events. Vascepa is a purified Omega-3 fatty acid product, derived from fish oil. Similar products are marketed directly to consumers by other companies under the FDA’s less-stringent dietary supplement regulations.

Amarin sought approval for Vascepa to treat adults with lower but still-high triglyceride levels (200 to 499 mg/dL) who are already being treated with statins for cholesterol (“persistently high” triglycerides). Vascepa passed an additional clinical trial in 2013, but the FDA withheld approval because studies using other, unrelated triglyceride-reducing drugs found that reduced triglycerides did not reduce the risk of cardiovascular events. FDA delayed approval pending the outcome of yet another study in which Amarin was already participating, designed to test directly Vascepa’s impact on risk of cardiovascular events. FDA warned Amarin not to promote Vascepa off-label, or risk prosecution.

Legal Background

The Food, Drug, and Cosmetic Act (FDCA) contains a criminal provision against selling (in interstate commerce) any drug that is “misbranded,”3 which the FDCA defines as lacking “adequate directions for use.”4 FDA regulation interprets as “adequate” directions that a layperson can use to take the drug safely “for the purposes for which it is intended.”5 The same regulations interpret “intended use” as the “objective intent” of the manufacturer, as demonstrated by oral and written statements and whether the drug is “offered and used for a purpose for which it is neither labeled nor advertised” with the manufacturer’s knowledge.6 The FDA takes the position that off-label promotion alters the “intended use” of the drug, rendering a drug misbranded.

The FDA has further taken the position that the truthfulness of the off-label promotion is irrelevant, since the prosecution is for the misbranded sales, not the promotional speech. In U.S. v. Caronia, however, the Second Circuit overturned the misbranding conviction of Alfred Caronia, a pharmaceutical representative, on First Amendment grounds.7 After looking closely at the trial record, the Second Circuit determined that in effect, Caronia had been convicted solely on the basis of his speech. Applying the Central Hudson test8 for commercial free speech, the Second Circuit found that the misbranding offense would violate the First Amendment, because it fails to directly advance the government interest in safe and effective pharmaceutical use, and is not narrowly drawn to restrict speech by the minimal degree necessary to advance that interest.9 The Second Circuit interpreted the FDCA misbranding provision consistent with the First Amendment, to exempt truthful, non-misleading speech that promotes an off-label use.10

Amarin Sues for Injunctive or Declaratory Relief

On May 7, 2015, Amarin brought an “as-applied” First Amendment challenge to the FDA’s position concerning Amarin’s prospective off-label promotion of Vascepa. Citing Caronia, Amarin argued that its First Amendment right to free speech was chilled by the threat of criminal prosecution. While final decision on the merits is pending, Amarin requested either a preliminary injunction against prosecution or a declaration that its planned promotional speech – a textual statement appended to the complaint – would not violate the misbranding provision. In opposition, the FDA attempted to distinguish Caronia, arguing that the misbranding statute in the abstract punished conduct of selling misbranded drugs, and that the Caronia decision only rejected as unconstitutional the prosecution’s strategy against Alfred Caronia, which impermissibly focused on his promotional speech rather than the sales.11 While maintaining the authority to prosecute even truthful and non-misleading off-label promotions, the FDA also proposed modifications to Amarin’s proposed text, offering assurances against prosecution if those modifications were adopted.

The Amarin Decision

In granting Amarin the requested relief, the Court rejected the FDA’s attempt to limit Caronia to its facts and concluded that the impact of the Caronia ruling was broader in scope. The Court ruled that the misbranding statute itself, not the wording of the prosecution’s case, is what criminalizes speech. The Court’s interpretation prevents the government from evading constitutional protections on truthful and non-misleading promotional speech by simply emphasizing the non-speech aspects of the offense.

The Court was not persuaded by the FDA’s efforts to defend its regulatory framework. As the Court noted, the FDCA’s misbranding provision dates to 1962, and the Supreme Court’s entire commercial speech doctrine is of a newer vintage. “The short answer is that the FDCA’s drug-approval framework predates modern First Amendment law respecting commercial speech.”12

Having decided that Caronia applied to Amarin’s situation, the Court unsurprisingly found that Amarin was likely to succeed on the merits and granted the preliminary relief sought. The court declared first that Amarin may engage in truthful, non-misleading off-label promotion of Vascepa for treating “persistently high triglycerides” without fear of misbranding prosecution, and second that certain specific text was truthful and non-misleading.

The approved text, however, is not the one that Amarin proposed. The Court modified Amarin’s proposal extensively. In some places, the Court added phrases that the FDA had suggested. In other places, the Court took Amarin’s proposal unaltered. Most remarkably, in the crucial passage concerning the drug’s impact on risk of cardiovascular event, the Court constructed a paragraph borrowing phrases from both Amarin’s and the FDA’s proposals but also including entirely new material supplied by the Court.13 Until the Court enters a final judgment or modifies its preliminary relief, only this approved text is safe from prosecution for misbranding.

Putting Amarin in Context

The Amarin decision required Judge Engelmayer to undertake a weighty proactive task: crafting a non-misleading message that the manufacturer could use to promote the proposed off-label use. The court’s approach arguably demands a high degree of confidence in the conclusion that this approved text is truthful and not misleading – and that the promoted use is safe. It is difficult to imagine the court adopting the same approach if the drug’s safety were at all in dispute, because the risk of harm to patients might bear more heavily on the public interest prong of the preliminary injunction analysis.14 Even in this case where the FDA conceded that Vascepa was safe, the court warned that its provisional remedy was “based on the present record,” and contingent on “changed circumstances” in scientific understanding.15

First Amendment Implications

From one First Amendment perspective, Amarin offers a cure that is perhaps worse than the disease. Amarin sought judicial approval for a specific text before actually using the speech, arguably acquiescing to a form of “prior restraint.” As the Court noted, “the FDA cannot require a manufacturer to choreograph its truthful promotional speech to conform to the agency’s specifications,” yet this opinion requires that the speech be choreographed to the Court’s specifications.16 If pre-emptive suits like this one become de rigueur, seeking judicial pre-clearance to market off-label, this practice itself could be viewed as in effect ad hoc censorship, enforced by the peril of criminal prosecution.

Implications for the False Claims Act

Beyond criminal misbranding prosecutions, the government can pursue off-label promotions for civil damages and penalties as violations of the False Claims Act (FCA). The FCA gives the government (or a “relator”: a whistleblower suing on behalf of the government) a civil claim against a defendant who obtains payment from the government by presenting a false claim for payment, by causing such a false claim to be presented, or by using or causing the use of a false record in making a claim.17 With few exceptions, off-label uses are not covered by Medicare, Medicaid, or other government payers, so the government has sued manufacturers for promoting off-label use of prescription drugs; specifically, for causing doctors and pharmacists to present claims for payment for drugs not covered by the government program, thereby rendering the claims “false”.

A pair of recent FCA cases against off-label promoters rejected the First Amendment defense.18 In both cases, however, the relators survived a motion to dismiss simply by pleading that the promotional speech was in fact false or misleading.19 Under the first step of the Central Hudson analysis, the allegation that the speech was false or misleading puts the speech entirely outside First Amendment protection, at least at the pleadings stage, where the court must treat allegations as true.

In Parke-Davis, an earlier FCA case, the court rejected a defense that “impermissible off-label promotion does not necessarily include a false statement or fraudulent conduct.”20 The court observed that the FCA violation arises from the submission of a claim to the government and not solely from the promotional speech itself.21 This distinction of the speech from the allegedly improper conduct is noteworthy, because Amarin and Caronia looked past the sales that nominally constitute the FDCA “misbranding” violation to give constitutional protection to the promotional speech.22 The Parke-Davis court suggested in dicta, without mentioning the First Amendment, that a “much closer question would be presented if the allegations involved only the unlawful—yet truthful—promotion of off-label uses . . . without any fraudulent representations by the manufacturer.”23 This dictum suggests that the logic of Caronia and the Free Speech defense might extend to FCA cases or to cases where the government has asserted FCA and FDCA misbranding claims in tandem.

The Narrow Path Forward

To many observers, Amarin opens a straight but ultimately narrow pathway for promoting off-label use. Only entirely truthful and non-misleading statements can be protected from prosecution. Although the Court’s declaration protects all truthful and non-misleading off-label promotion of Vascepa, only the approved text, as modified by the court, has been declared truthful and non-misleading. Any statement beyond the approved “textual statements” is potentially subject to criminal prosecution. If the pre-clearance of text through declaratory relief becomes standard procedure, compliance personnel will have to continue to vigilantly oversee and monitor the statements of drug sales representatives and others to ensure that their statements adhere to the script; any oral or written statement augmenting or otherwise deviating from the approved text might only increase the risk of prosecution. Underscoring this warning to the industry, the Court cautions that: “A manufacturer that leaves its sales force at liberty to converse unscripted with doctors about off-label use of an approved drug invites a misbranding action if false or misleading (e.g., one-sided or incomplete) representations result.”24

1 Amarin Pharma, Inc. v. Food & Drug Admin., 15-CV-3588 (S.D.N.Y. Aug. 7, 2015) (Engelmayer, J.).

2 U.S. v. Caronia, 703 F.3d 149 (2d Cir. 2012). The Caronia decision has been the subject of Cadwalader Client & Friends Memos on January 4, 2013 and April 21, 2014.

3 21 U.S.C. § 331(a).

4 21 U.S.C. § 352(f).

5 21 C.F.R. § 201.5.

6 21 C.F.R. § 201.128.

7 U.S. v. Caronia, 703 F.3d 149 (2d Cir. 2012).

8 Central Hudson Gas & Electric Corp. v. Public Service Comm'n of N.Y., 447 U.S. 557, 566 (1980). Central Hudson is a four-part analysis: (1) commercial speech is protected by the First Amendment only if it concerns lawful activity and is non-misleading; (2) government must justify restrictions on protected commercial speech by articulating a "substantial" governmental interest; (3) the regulation is permissible only if it "directly advances" that substantial governmental interest; and (4) the regulation must be no more extensive than necessary to serve the stated interest.

9 Caronia, 703 F.3d at 166-69.

10 The Second Circuit's quotes from the trial record strongly suggest that Caronia had made misleading statements to promote off-label use, but "[t]he government did not argue at trial, nor [did] it argue on appeal, that the promotion in question was false or misleading." Caronia, 703 F.3d at 165-66 n.10. "Of course, off-label promotion that is false or misleading is not entitled to First Amendment protection." Id.

11 Amarin at 44-46.

12 Amarin at 49.

13 Amarin at 57-60.

14 Amarin at 67-68 (no public interest in delaying off-label promotion because "FDA has acknowledged that it has no evidence that Vascepa is harmful").

15 Amarin at 66.

16 Amarin at 53.

17 31 U.S.C. § 3729(a).

18 U.S. ex rel. Bergman v. Abbot Laboratories, 995 F. Supp. 2d 357, 375-76 (E.D. Pa. 2014); U.S. ex rel. Cestra v. Cephalon, Inc., 14-CV-1842, 2015 WL 3498761 at *12 (E.D. Pa. June 3, 2015). The then-pending Cephalon case was addressed in Cadwalader's April 21, 2014 Client & Friends Memo.

19 Abbot Labs, 995 F. Supp. 2d at 376; Cephalon, 2015 WL 3498761 at *12 (distinguishing Caronia because it "concerned First Amendment protection for truthful speech and did not consider whether allegedly false and misleading off-label promotion is entitled to First Amendment protection.")

20 U.S. ex rel. Franklin v. Parke-Davis, Div. of Warner-Lambert Co., 147 F. Supp. 2d 39, 52 (D. Mass. 2001).

21 Id.

22 Amarin at 46; Caronia, 703 F.3d at 162.

23 Parke-Davis, 147 F. Supp. 2d at 52. Parke-Davis was in fact alleged to have used misleading statements in its off-label promotion, although that was not a required element of the FCA claim.

24 Amarin at 53. This warning confirms that no split exists between the Second Circuit's Caronia decision and the 9th Circuit's U.S. v. Harkonen, 510 Fed. Appx. 633, 636 (9th Cir. 2013) (affirming wire fraud conviction of CEO who promoted off-label use because "[t]he First Amendment does not protect fraudulent speech"). The Harkonen decision is the subject of Cadwalader's March 22, 2013 Client & Friends Memo.

The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.

To print this article, all you need is to be registered on Mondaq.com.

Click to Login as an existing user or Register so you can print this article.

In association with
Related Video
Up-coming Events Search
Font Size:
Mondaq on Twitter
Register for Access and our Free Biweekly Alert for
This service is completely free. Access 250,000 archived articles from 100+ countries and get a personalised email twice a week covering developments (and yes, our lawyers like to think you’ve read our Disclaimer).
Email Address
Company Name
Confirm Password
Mondaq Topics -- Select your Interests
 Law Performance
 Law Practice
 Media & IT
 Real Estate
 Wealth Mgt
Asia Pacific
European Union
Latin America
Middle East
United States
Worldwide Updates
Check to state you have read and
agree to our Terms and Conditions

Terms & Conditions and Privacy Statement

Mondaq.com (the Website) is owned and managed by Mondaq Ltd and as a user you are granted a non-exclusive, revocable license to access the Website under its terms and conditions of use. Your use of the Website constitutes your agreement to the following terms and conditions of use. Mondaq Ltd may terminate your use of the Website if you are in breach of these terms and conditions or if Mondaq Ltd decides to terminate your license of use for whatever reason.

Use of www.mondaq.com

You may use the Website but are required to register as a user if you wish to read the full text of the content and articles available (the Content). You may not modify, publish, transmit, transfer or sell, reproduce, create derivative works from, distribute, perform, link, display, or in any way exploit any of the Content, in whole or in part, except as expressly permitted in these terms & conditions or with the prior written consent of Mondaq Ltd. You may not use electronic or other means to extract details or information about Mondaq.com’s content, users or contributors in order to offer them any services or products which compete directly or indirectly with Mondaq Ltd’s services and products.


Mondaq Ltd and/or its respective suppliers make no representations about the suitability of the information contained in the documents and related graphics published on this server for any purpose. All such documents and related graphics are provided "as is" without warranty of any kind. Mondaq Ltd and/or its respective suppliers hereby disclaim all warranties and conditions with regard to this information, including all implied warranties and conditions of merchantability, fitness for a particular purpose, title and non-infringement. In no event shall Mondaq Ltd and/or its respective suppliers be liable for any special, indirect or consequential damages or any damages whatsoever resulting from loss of use, data or profits, whether in an action of contract, negligence or other tortious action, arising out of or in connection with the use or performance of information available from this server.

The documents and related graphics published on this server could include technical inaccuracies or typographical errors. Changes are periodically added to the information herein. Mondaq Ltd and/or its respective suppliers may make improvements and/or changes in the product(s) and/or the program(s) described herein at any time.


Mondaq Ltd requires you to register and provide information that personally identifies you, including what sort of information you are interested in, for three primary purposes:

  • To allow you to personalize the Mondaq websites you are visiting.
  • To enable features such as password reminder, newsletter alerts, email a colleague, and linking from Mondaq (and its affiliate sites) to your website.
  • To produce demographic feedback for our information providers who provide information free for your use.

Mondaq (and its affiliate sites) do not sell or provide your details to third parties other than information providers. The reason we provide our information providers with this information is so that they can measure the response their articles are receiving and provide you with information about their products and services.

If you do not want us to provide your name and email address you may opt out by clicking here .

If you do not wish to receive any future announcements of products and services offered by Mondaq by clicking here .

Information Collection and Use

We require site users to register with Mondaq (and its affiliate sites) to view the free information on the site. We also collect information from our users at several different points on the websites: this is so that we can customise the sites according to individual usage, provide 'session-aware' functionality, and ensure that content is acquired and developed appropriately. This gives us an overall picture of our user profiles, which in turn shows to our Editorial Contributors the type of person they are reaching by posting articles on Mondaq (and its affiliate sites) – meaning more free content for registered users.

We are only able to provide the material on the Mondaq (and its affiliate sites) site free to site visitors because we can pass on information about the pages that users are viewing and the personal information users provide to us (e.g. email addresses) to reputable contributing firms such as law firms who author those pages. We do not sell or rent information to anyone else other than the authors of those pages, who may change from time to time. Should you wish us not to disclose your details to any of these parties, please tick the box above or tick the box marked "Opt out of Registration Information Disclosure" on the Your Profile page. We and our author organisations may only contact you via email or other means if you allow us to do so. Users can opt out of contact when they register on the site, or send an email to unsubscribe@mondaq.com with “no disclosure” in the subject heading

Mondaq News Alerts

In order to receive Mondaq News Alerts, users have to complete a separate registration form. This is a personalised service where users choose regions and topics of interest and we send it only to those users who have requested it. Users can stop receiving these Alerts by going to the Mondaq News Alerts page and deselecting all interest areas. In the same way users can amend their personal preferences to add or remove subject areas.


A cookie is a small text file written to a user’s hard drive that contains an identifying user number. The cookies do not contain any personal information about users. We use the cookie so users do not have to log in every time they use the service and the cookie will automatically expire if you do not visit the Mondaq website (or its affiliate sites) for 12 months. We also use the cookie to personalise a user's experience of the site (for example to show information specific to a user's region). As the Mondaq sites are fully personalised and cookies are essential to its core technology the site will function unpredictably with browsers that do not support cookies - or where cookies are disabled (in these circumstances we advise you to attempt to locate the information you require elsewhere on the web). However if you are concerned about the presence of a Mondaq cookie on your machine you can also choose to expire the cookie immediately (remove it) by selecting the 'Log Off' menu option as the last thing you do when you use the site.

Some of our business partners may use cookies on our site (for example, advertisers). However, we have no access to or control over these cookies and we are not aware of any at present that do so.

Log Files

We use IP addresses to analyse trends, administer the site, track movement, and gather broad demographic information for aggregate use. IP addresses are not linked to personally identifiable information.


This web site contains links to other sites. Please be aware that Mondaq (or its affiliate sites) are not responsible for the privacy practices of such other sites. We encourage our users to be aware when they leave our site and to read the privacy statements of these third party sites. This privacy statement applies solely to information collected by this Web site.

Surveys & Contests

From time-to-time our site requests information from users via surveys or contests. Participation in these surveys or contests is completely voluntary and the user therefore has a choice whether or not to disclose any information requested. Information requested may include contact information (such as name and delivery address), and demographic information (such as postcode, age level). Contact information will be used to notify the winners and award prizes. Survey information will be used for purposes of monitoring or improving the functionality of the site.


If a user elects to use our referral service for informing a friend about our site, we ask them for the friend’s name and email address. Mondaq stores this information and may contact the friend to invite them to register with Mondaq, but they will not be contacted more than once. The friend may contact Mondaq to request the removal of this information from our database.


From time to time Mondaq may send you emails promoting Mondaq services including new services. You may opt out of receiving such emails by clicking below.

*** If you do not wish to receive any future announcements of services offered by Mondaq you may opt out by clicking here .


This website takes every reasonable precaution to protect our users’ information. When users submit sensitive information via the website, your information is protected using firewalls and other security technology. If you have any questions about the security at our website, you can send an email to webmaster@mondaq.com.

Correcting/Updating Personal Information

If a user’s personally identifiable information changes (such as postcode), or if a user no longer desires our service, we will endeavour to provide a way to correct, update or remove that user’s personal data provided to us. This can usually be done at the “Your Profile” page or by sending an email to EditorialAdvisor@mondaq.com.

Notification of Changes

If we decide to change our Terms & Conditions or Privacy Policy, we will post those changes on our site so our users are always aware of what information we collect, how we use it, and under what circumstances, if any, we disclose it. If at any point we decide to use personally identifiable information in a manner different from that stated at the time it was collected, we will notify users by way of an email. Users will have a choice as to whether or not we use their information in this different manner. We will use information in accordance with the privacy policy under which the information was collected.

How to contact Mondaq

You can contact us with comments or queries at enquiries@mondaq.com.

If for some reason you believe Mondaq Ltd. has not adhered to these principles, please notify us by e-mail at problems@mondaq.com and we will use commercially reasonable efforts to determine and correct the problem promptly.