United States: The Past, Present, And Future Of Government Regulation Of Off-Label Communications – Part 3

This is Part 3 in my series exploring the history of FDA's regulation of off-label communications, which has become newly relevant in light of the recent events highlighted in Part 1. In this installment, I continue describing how FDA's regulatory scheme has persisted in light of the key First Amendment decisions involving off-label promotion. Even though FDA hesitated in and ultimately rejected promulgating regulations that would make any action "that directly or indirectly suggests to the physician or to the patient that an approved drug may properly be used for unapproved uses for which it is neither labeled nor advertised" (37 Fed. Reg. 16,503, 16,504) into a matter warranting enforcement action, the Agency used this reasoning to shape an off-label communication policy. As I described in Part 2, FDA's policy enjoyed some support from federal courts; however, this support was only temporary. More recently, federal courts have shown support for the idea that truthful and non-misleading promotions of off-label uses of drugs and devices by manufacturers are protected under the First Amendment. A review of the pivotal cases in this area will help put FDA's off-label policy in perspective, especially in light of FDA's reaction to these cases in a memorandum published in January 2017.

Washington Legal Foundation and Aftermath as the Backdrop for Caronia and Later Cases

In 1998, the U.S. District Court for the District of Columbia ruled that FDA's guidance documents Industry-Supported Scientific and Educational Activities (62 Fed. Reg. 64,074 (1997)) and Advertising and Promotion (61 Fed. Reg. 52,800 (1996)) were unconstitutional because they unduly burdened manufacturers' First Amendment right to provide physicians with truthful and nonmisleading information on off-label uses. With respect to the first element of the Central Hudson test (whether the commercial speech concerns a lawful activity and the speech is not misleading), a pivotal consideration in this case, FDA attempted to show that off-label communication itself is an illegal activity by arguing, in the words of the court, that "a drug or device is considered to be misbranded as a matter of law if it is promoted by the manufacturer for an off-label use . . . [and t]herefore, when a manufacturer disseminates information about a drug product that diverges from the treatments included on the label, that manufacturer may be engaged in misbranding, which is illegal" (Wash. Legal Found. v. Friedman). The court rejected that reasoning, stating that the underlying activity promoted by the off-label communication, as speech, is a physician prescribing drugs or devices off-label, which is legal. The court went on to find that off-label communications are protected commercial speech and that the Central Hudson test weighed in favor of protecting such communications against FDA's regulatory overreach. This decision set the stage for FDA to strike the guidance documents and reconsider its off-label policy.

After the decision in Washington Legal Foundation, however, the Food and Drug Administration Modernization Act of 1997 (FDAMA) went into effect, which contained explicit provisions describing acceptable circumstances in which manufacturers could provide off-label information to health care professionals. The effect of FDAMA was the key consideration in the appeal of the district court's ruling, Washington Legal Foundation v. Henney. By the D.C. Circuit Court of Appeal's description, FDA appeared confused about its own policy after FDAMA: "At times the FDA appeared to share WLF's assessment that [FDAMA] provide legal authorization to restrict manufacturer speech, but more frequently the FDA asserted that [FDAMA] established nothing more than a 'safe harbor' ensuring that certain forms of conduct would not be used against manufacturers in misbranding and 'intended use' enforcement actions based on pre-existing legislative authority" (202 F.3d 331 at 335). Ultimately, FDA chose to view FDAMA as providing a safe harbor, admitting "[w]ere a pharmaceutical company to send out reprints of an article devoted to its drug's off-label uses to thousands of physicians tomorrow . . . the agency would draw no independent prosecutorial authority from FDAMA to buttress any enforcement proceeding" and "noting in [FDAMA] provides the FDA with independent authority to regulate manufacturer speech" (id. at 335-336). In light of those concessions, the Washington Legal Foundation dropped its claim and the D.C. Circuit dismissed the case.

Although there was no lasting, enforceable legal rebuke to FDA's off-label policy from the Washington Legal Foundation cases, the analyses provided by the courts involved laid the foundation for subsequent courts to determine the First Amendment implications of off-label communication regulations.

The Next Era: Sorrell, Caronia, Amarin, and Vascular Solutions

The question of the whether promotion of drugs and devices by manufacturers is protected speech arose again in 2007 when Vermont passed a law essentially prohibiting manufacturer access to prescriber-identifying information, which was challenged in court. The case made its way to the U.S. Supreme Court as Sorrell v. IMS Health Inc. Importantly, the Court held that "[s]peech in aid of pharmaceutical marketing . . . is a form of expression protected by the Free Speech Clause of the First Amendment" and found that the state did not overcome its burden to show that the restriction leveled only at manufacturers advanced a substantial government interest, as required under Central Hudson.

Sorrell further paved the way for the subsequent decisions in U.S. v. Caronia, Amarin Pharma, Inc. v. FDA, and U.S. v. Vascular Solutions, Inc. It is not my intention to repeat all of the details and holdings in each of these cases here, as this blog has previously analyzed these three critical off-label communication cases: see our analyses of Caronia here and here, Amarin here and here, and Vascular Solutions here and here. Suffice it to say, that the U.S. Supreme Court, the U.S. Court of Appeals for the Second Circuit, and multiple federal district courts now appear to recognize that (1) truthful and non-misleading off-label communications related FDA-regulated products are protected under the First Amendment and (2) the mere act of making truthful and non-misleading off-label communications is not, in itself, a prosecutable offence under 21 U.S.C. § 331(a).

FDA's Defensive Response to All Off-Label Cases

I have already blogged on FDA's January 2017 memo, which offered a defense of its historical off-label communication policy. However, the Agency's memo warrants revisiting in light of the subject matter of this post.

In the memo, FDA assails the recent federal court decisions on off-label communications. First, FDA argues that the Caronia court considered only a narrow construction of the Food, Drug, and Cosmetic Act's misbranding provisions and did not evaluate the Agency's "implementation approach," including guidances and policies exempting certain communications from determinations of intended use (FDA memo at 23). In fact, the Second Circuit went to great lengths in Caronia to recommend to FDA alternative methods to implement restrictions on off-label communications that would be more likely to pass constitutional muster. Also, both Washington Legal Foundation and Amarin delved into elements of FDA's implementation approach and still found it lacking from a constitutional perspective.

Second, FDA asserts that the Second Circuit did not consider all of FDA's interests in preventing manufacturers from promoting off-label uses of drugs and devices. Remember though, the Agency did not submit a writ of certiorari to the U.S. Supreme Court after the Second Circuit's decision in Caronia, which makes the memo's assertion fall flat. Also, the memo argues that new evidence presented in a Canadian study "showing an association between unapproved uses and adverse drug events" had it been available to the court may have changed the Second Circuit's decision (FDA memo at 23-24). FDA is merely repeating here, and in the rest of the January memo, its defense in Caronia that the Agency must restrict off-label promotion by manufacturers for the good of public health. However, the Second Circuit rejected this argument:

The government's construction of the FDCA essentially legalizes the outcome—off-label use—but prohibits the free flow of information that would inform that outcome. If the government's objective is to shepherd physicians to prescribe drugs only on-label, criminalizing manufacturer promotion of off-label use while permitting others to promote such use to physicians is an indirect and questionably effective means to achieve that goal. (703 F.3d 149, 167)

FDA's memo is another attempt at the end of an outgoing presidential administration to defend its policy that a physician prescribing a drug or device off-label is permissible but providing physicians accurate, non-misleading information about off-label uses when such communications are connected to promotional activities is not.

Third, despite the rulings in Sorrell, Caronia, and Amarin FDA tries to find support for its position that content- and speaker-based limitations on speech is permissible in the context of off-label promotion. In the memo, the Agency holds to its argument that only FDA's established approval process can distinguish safe and effective from dangerous and harmful, and that less than absolute proof of product safety and effectiveness through the formal FDA approval process leads to patient harm. The memo even goes so far as to cite the dissenting opinions in Sorrell and Caronia in support of its argument that "even if these restrictions on firm activity were viewed as commercial speech restrictions, they are necessarily both speaker- and content-based as part of reasonable government regulation of particular industries in the interest of greater public good" (FDA memo at 25). In light of multiple courts' examinations of this same defense, FDA's maintenance of this argument seems weak, especially in light of FDA's rejection of each regulatory alternative offered in Caronia and through public comments.

FDA's arguments demonstrate that the Agency is sticking to its position that off-label communications by manufacturers cause more harm than good and prohibitions should be strictly enforced. A position that appears to be at odds with FDA's own statement in the public settlement resulting from Amarin, in which FDA recognizes that "truthful, non-misleading speech promoting...off-label use...may not form the bases of a prosecution for misbranding" (Document 83 in 1:15-cv-03588-PAE).

Time will tell whether FDA's policy will evolve beyond the January memo and incorporate the results of judicial decisions under the Trump administration.

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.

Authors
Similar Articles
Relevancy Powered by MondaqAI
 
In association with
Related Topics
 
Similar Articles
Relevancy Powered by MondaqAI
Related Articles
 
Related Video
Up-coming Events Search
Tools
Print
Font Size:
Translation
Channels
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
Password
Confirm Password
Position
Mondaq Topics -- Select your Interests
 Accounting
 Anti-trust
 Commercial
 Compliance
 Consumer
 Criminal
 Employment
 Energy
 Environment
 Family
 Finance
 Government
 Healthcare
 Immigration
 Insolvency
 Insurance
 International
 IP
 Law Performance
 Law Practice
 Litigation
 Media & IT
 Privacy
 Real Estate
 Strategy
 Tax
 Technology
 Transport
 Wealth Mgt
Regions
Africa
Asia
Asia Pacific
Australasia
Canada
Caribbean
Europe
European Union
Latin America
Middle East
U.K.
United States
Worldwide Updates
Registration (you must scroll down to set your data preferences)

Mondaq Ltd requires you to register and provide information that personally identifies you, including your content preferences, for three primary purposes (full details of Mondaq’s use of your personal data can be found in our Privacy and Cookies Notice):

  • To allow you to personalize the Mondaq websites you are visiting to show content ("Content") relevant to your interests.
  • To enable features such as password reminder, news alerts, email a colleague, and linking from Mondaq (and its affiliate sites) to your website.
  • To produce demographic feedback for our content providers ("Contributors") who contribute Content for free for your use.

Mondaq hopes that our registered users will support us in maintaining our free to view business model by consenting to our use of your personal data as described below.

Mondaq has a "free to view" business model. Our services are paid for by Contributors in exchange for Mondaq providing them with access to information about who accesses their content. Once personal data is transferred to our Contributors they become a data controller of this personal data. They use it to measure the response that their articles are receiving, as a form of market research. They may also use it to provide Mondaq users with information about their products and services.

Details of each Contributor to which your personal data will be transferred is clearly stated within the Content that you access. For full details of how this Contributor will use your personal data, you should review the Contributor’s own Privacy Notice.

Please indicate your preference below:

Yes, I am happy to support Mondaq in maintaining its free to view business model by agreeing to allow Mondaq to share my personal data with Contributors whose Content I access
No, I do not want Mondaq to share my personal data with Contributors

Also please let us know whether you are happy to receive communications promoting products and services offered by Mondaq:

Yes, I am happy to received promotional communications from Mondaq
No, please do not send me promotional communications from Mondaq
Terms & Conditions

Mondaq.com (the Website) is owned and managed by Mondaq Ltd (Mondaq). Mondaq grants you a non-exclusive, revocable licence to access the Website and associated services, such as the Mondaq News Alerts (Services), subject to and in consideration of your compliance with the following terms and conditions of use (Terms). Your use of the Website and/or Services constitutes your agreement to the Terms. Mondaq may terminate your use of the Website and Services if you are in breach of these Terms or if Mondaq decides to terminate the licence granted hereunder for any reason whatsoever.

Use of www.mondaq.com

To Use Mondaq.com you must be: eighteen (18) years old or over; legally capable of entering into binding contracts; and not in any way prohibited by the applicable law to enter into these Terms in the jurisdiction which you are currently located.

You may use the Website as an unregistered user, however, you are required to register as a user if you wish to read the full text of the Content or to receive the Services.

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 or with the prior written consent of Mondaq. You may not use electronic or other means to extract details or information from the Content. Nor shall you extract information about users or Contributors in order to offer them any services or products.

In your use of the Website and/or Services you shall: comply with all applicable laws, regulations, directives and legislations which apply to your Use of the Website and/or Services in whatever country you are physically located including without limitation any and all consumer law, export control laws and regulations; provide to us true, correct and accurate information and promptly inform us in the event that any information that you have provided to us changes or becomes inaccurate; notify Mondaq immediately of any circumstances where you have reason to believe that any Intellectual Property Rights or any other rights of any third party may have been infringed; co-operate with reasonable security or other checks or requests for information made by Mondaq from time to time; and at all times be fully liable for the breach of any of these Terms by a third party using your login details to access the Website and/or Services

however, you shall not: do anything likely to impair, interfere with or damage or cause harm or distress to any persons, or the network; do anything that will infringe any Intellectual Property Rights or other rights of Mondaq or any third party; or use the Website, Services and/or Content otherwise than in accordance with these Terms; use any trade marks or service marks of Mondaq or the Contributors, or do anything which may be seen to take unfair advantage of the reputation and goodwill of Mondaq or the Contributors, or the Website, Services and/or Content.

Mondaq reserves the right, in its sole discretion, to take any action that it deems necessary and appropriate in the event it considers that there is a breach or threatened breach of the Terms.

Mondaq’s Rights and Obligations

Unless otherwise expressly set out to the contrary, nothing in these Terms shall serve to transfer from Mondaq to you, any Intellectual Property Rights owned by and/or licensed to Mondaq and all rights, title and interest in and to such Intellectual Property Rights will remain exclusively with Mondaq and/or its licensors.

Mondaq shall use its reasonable endeavours to make the Website and Services available to you at all times, but we cannot guarantee an uninterrupted and fault free service.

Mondaq reserves the right to make changes to the services and/or the Website or part thereof, from time to time, and we may add, remove, modify and/or vary any elements of features and functionalities of the Website or the services.

Mondaq also reserves the right from time to time to monitor your Use of the Website and/or services.

Disclaimer

The Content is general information only. It is not intended to constitute legal advice or seek to be the complete and comprehensive statement of the law, nor is it intended to address your specific requirements or provide advice on which reliance should be placed. Mondaq and/or its Contributors and other suppliers make no representations about the suitability of the information contained in the Content for any purpose. All Content provided "as is" without warranty of any kind. Mondaq and/or its Contributors and other suppliers hereby exclude and disclaim all representations, warranties or guarantees with regard to the Content, including all implied warranties and conditions of merchantability, fitness for a particular purpose, title and non-infringement. To the maximum extent permitted by law, Mondaq expressly excludes all representations, warranties, obligations, and liabilities arising out of or in connection with all Content. In no event shall Mondaq 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 of the Content or performance of Mondaq’s Services.

General

Mondaq may alter or amend these Terms by amending them on the Website. By continuing to Use the Services and/or the Website after such amendment, you will be deemed to have accepted any amendment to these Terms.

These Terms shall be governed by and construed in accordance with the laws of England and Wales and you irrevocably submit to the exclusive jurisdiction of the courts of England and Wales to settle any dispute which may arise out of or in connection with these Terms. If you live outside the United Kingdom, English law shall apply only to the extent that English law shall not deprive you of any legal protection accorded in accordance with the law of the place where you are habitually resident ("Local Law"). In the event English law deprives you of any legal protection which is accorded to you under Local Law, then these terms shall be governed by Local Law and any dispute or claim arising out of or in connection with these Terms shall be subject to the non-exclusive jurisdiction of the courts where you are habitually resident.

You may print and keep a copy of these Terms, which form the entire agreement between you and Mondaq and supersede any other communications or advertising in respect of the Service and/or the Website.

No delay in exercising or non-exercise by you and/or Mondaq of any of its rights under or in connection with these Terms shall operate as a waiver or release of each of your or Mondaq’s right. Rather, any such waiver or release must be specifically granted in writing signed by the party granting it.

If any part of these Terms is held unenforceable, that part shall be enforced to the maximum extent permissible so as to give effect to the intent of the parties, and the Terms shall continue in full force and effect.

Mondaq shall not incur any liability to you on account of any loss or damage resulting from any delay or failure to perform all or any part of these Terms if such delay or failure is caused, in whole or in part, by events, occurrences, or causes beyond the control of Mondaq. Such events, occurrences or causes will include, without limitation, acts of God, strikes, lockouts, server and network failure, riots, acts of war, earthquakes, fire and explosions.

By clicking Register you state you have read and agree to our Terms and Conditions