The Past, Present, and Future of Government Regulation of Off-Label Communications – Part 4

by Mintz Levin - Health Law & Policy Matters

Picking up from my last installment of this series exploring the regulatory history of off-label communication, this post highlights some recent trends in FDA enforcement and guidance related to off-label promotion.  Not surprisingly, FDA has taken a hard-line approach in its guidance on off-label communications, similar to the Agency’s forceful January 2017 memo. This aggressive stance has not, however, translated into increased enforcement.

Recent Off-Label Enforcement Trends

In large part, FDA’s Office of Prescription Drug Promotion (“OPDP”) handles violations involving promotional content in drug labeling, including promotional material presented on television, print media, the internet, and at trade shows and conferences.  Given this responsibility, OPDP is the FDA division most likely to identify instances of off-label promotion by manufacturers and initiate enforcement action by sending a Warning Letter or Untitled Letter.

Considering FDA’s rejection of all alternative approaches to off-label communications recommended by the U.S. Court of Appeals for the Second Circuit in Caronia and during the November 2016 public meeting, one would expect active, strict enforcement of FDA’s off-label communication standards.  However, the reality is that OPDP has shown a significant decline in enforcement activity in recent years.  In 2010, OPDP issued 52 Warning and Untitled Letters, but by 2013, that number declined to 24 enforcement letters; less than half the number sent in 2010.  In 2015 and 2016, OPDP issued 9 and 11 enforcement letters, respectively, and so far in 2017, OPDP has issued only 1 Untitled Letter.  Enforcement related to off-label promotion is also low, as evidenced by OPDP issuing only 3 Untitled Letters citing manufacturer promotional materials containing information on new uses for which the drug lacks FDA approval.

In 2015, and in the midst of the Amarin case, FDA was forced to withdraw a Warning Letter as part of a settlement with the drug manufacturer Pacira.  In September 2014, OPDP issued a Warning Letter which stated that Pacira was marketing its postsurgical pain medication off-label and cited medical journal ads and administration guides.  The promotional materials stated that the drug could be used for pain relief after two specific types of surgery, uses which were not explicitly approved by FDA, even though FDA had approved an indication for the drug which encompassed broader postsurgical uses.  Pacira filed a lawsuit against FDA claiming that the enforcement action violated the company’s First Amendment rights, and obtained a settlement agreement in which FDA rescinded the Warning Letter and approved a labeling supplement which clarified the drug’s prescribing information.

In light of the Pacira settlement, it appears that FDA now finds itself in a catch 22: the Agency wants to strengthen its aggressive policy to limit off-label communications by manufacturers, but it cannot effectively enforce that policy because manufacturers are finding support for their First Amendment defense in federal courts.

FDA’s Recent Guidance Related to Off-Label Communications

When it comes to guidance on prescription drug promotional materials, FDA staunchly holds to its three core tenets developed decades ago: promotional materials must (1) be accurate and not misleading, (2) contain a fair balance of benefit and risk information, and (3) be adequately substantiated by supporting scientific data.  In general, all FDA guidance on promotional activities is based on these core standards.  However, even when a manufacturer can meet all of these standards by limiting off-label communications to those that are accurate with respect to completed scientific studies and that present the balance of benefits and risks, FDA still rejects such communications as illicit in a promotional context.  According to FDA’s January memo, the Agency’s position appears to be that it is the only arbiter of scientific validity and objectivity and that no promotional material may be considered accurate and non-misleading unless it passes official FDA scrutiny.

Recent FDA guidance documents bear out its hard-line approach to off-label communications.  In the draft guidance Medical Product Communications That Are Consistent With the FDA-Required Labeling — Questions and Answers released in January 2017, FDA sets out its position on medical product promotions that will not lead to enforcement action.  Essentially, the guidance reinforces FDA’s traditional stance on promotional materials and gives examples of communications that are not consistent with FDA-required labeling, including the following types of information:

  • Use of a product to treat or diagnose a different disease or condition that the product is approved/cleared to treat or diagnose;
  • Use of a product to treat or diagnose patients who are not in the approved/cleared patient population;
  • Use of product to treat a different, stage, severity, or manifestation of a disease than the product is approved/cleared to treat;
  • Use of a product as monotherapy when it is only approved/cleared for use in conjunction with one or more therapies;
  • Using a product through a different route of administration;
  • Use of a different strength, dosage, or use regimen than the approved/cleared strength, dosage, or use regimen; and
  • Use of a product in a different dosage form than the one described in FDA-required labeling.

These examples effectively encompass the major categories of potential off-label use and demonstrate FDA’s intent to initiate enforcement action against manufacturers that engage in off-label communications about medical products, regardless of the supporting data available.

[View source.]

DISCLAIMER: Because of the generality of this update, the information provided herein may not be applicable in all situations and should not be acted upon without specific legal advice based on particular situations.

© Mintz Levin - Health Law & Policy Matters | Attorney Advertising

Written by:

Mintz Levin - Health Law & Policy Matters

Mintz Levin - Health Law & Policy Matters on:

Readers' Choice 2017
Reporters on Deadline

"My best business intelligence, in one easy email…"

Your first step to building a free, personalized, morning email brief covering pertinent authors and topics on JD Supra:
Sign up using*

Already signed up? Log in here

*By using the service, you signify your acceptance of JD Supra's Privacy Policy.
Custom Email Digest
Privacy Policy (Updated: October 8, 2015):

JD Supra provides users with access to its legal industry publishing services (the "Service") through its website (the "Website") as well as through other sources. Our policies with regard to data collection and use of personal information of users of the Service, regardless of the manner in which users access the Service, and visitors to the Website are set forth in this statement ("Policy"). By using the Service, you signify your acceptance of this Policy.

Information Collection and Use by JD Supra

JD Supra collects users' names, companies, titles, e-mail address and industry. JD Supra also tracks the pages that users visit, logs IP addresses and aggregates non-personally identifiable user data and browser type. This data is gathered using cookies and other technologies.

The information and data collected is used to authenticate users and to send notifications relating to the Service, including email alerts to which users have subscribed; to manage the Service and Website, to improve the Service and to customize the user's experience. This information is also provided to the authors of the content to give them insight into their readership and help them to improve their content, so that it is most useful for our users.

JD Supra does not sell, rent or otherwise provide your details to third parties, other than to the authors of the content on JD Supra.

If you prefer not to enable cookies, you may change your browser settings to disable cookies; however, please note that rejecting cookies while visiting the Website may result in certain parts of the Website not operating correctly or as efficiently as if cookies were allowed.

Email Choice/Opt-out

Users who opt in to receive emails may choose to no longer receive e-mail updates and newsletters by selecting the "opt-out of future email" option in the email they receive from JD Supra or in their JD Supra account management screen.


JD Supra takes reasonable precautions to insure that user information is kept private. We restrict access to user information to those individuals who reasonably need access to perform their job functions, such as our third party email service, customer service personnel and technical staff. However, please note that no method of transmitting or storing data is completely secure and we cannot guarantee the security of user information. Unauthorized entry or use, hardware or software failure, and other factors may compromise the security of user information at any time.

If you have reason to believe that your interaction with us is no longer secure, you must immediately notify us of the problem by contacting us at In the unlikely event that we believe that the security of your user information in our possession or control may have been compromised, we may seek to notify you of that development and, if so, will endeavor to do so as promptly as practicable under the circumstances.

Sharing and Disclosure of Information JD Supra Collects

Except as otherwise described in this privacy statement, JD Supra will not disclose personal information to any third party unless we believe that disclosure is necessary to: (1) comply with applicable laws; (2) respond to governmental inquiries or requests; (3) comply with valid legal process; (4) protect the rights, privacy, safety or property of JD Supra, users of the Service, Website visitors or the public; (5) permit us to pursue available remedies or limit the damages that we may sustain; and (6) enforce our Terms & Conditions of Use.

In the event there is a change in the corporate structure of JD Supra such as, but not limited to, merger, consolidation, sale, liquidation or transfer of substantial assets, JD Supra may, in its sole discretion, transfer, sell or assign information collected on and through the Service to one or more affiliated or unaffiliated third parties.

Links to Other Websites

This Website and the Service may contain links to other websites. The operator of such other websites may collect information about you, including through cookies or other technologies. If you are using the Service through the Website and link to another site, you will leave the Website and this Policy will not apply to your use of and activity on those other sites. We encourage you to read the legal notices posted on those sites, including their privacy policies. We shall have no responsibility or liability for your visitation to, and the data collection and use practices of, such other sites. This Policy applies solely to the information collected in connection with your use of this Website and does not apply to any practices conducted offline or in connection with any other websites.

Changes in Our Privacy Policy

We reserve the right to change this Policy at any time. Please refer to the date at the top of this page to determine when this Policy was last revised. Any changes to our privacy policy will become effective upon posting of the revised policy on the Website. By continuing to use the Service or Website following such changes, you will be deemed to have agreed to such changes. If you do not agree with the terms of this Policy, as it may be amended from time to time, in whole or part, please do not continue using the Service or the Website.

Contacting JD Supra

If you have any questions about this privacy statement, the practices of this site, your dealings with this Web site, or if you would like to change any of the information you have provided to us, please contact us at:

- hide
*With LinkedIn, you don't need to create a separate login to manage your free JD Supra account, and we can make suggestions based on your needs and interests. We will not post anything on LinkedIn in your name. Or, sign up using your email address.