United States: FDA Issues Three Key Documents Relating To Medical Product Manufacturer Communications

On January 18, 2017, the Food and Drug Administration ("FDA") released three key documents outlining the agency's current thinking regarding drug and device manufacturers' communication of information not contained in FDA-approved labeling. FDA issued two draft guidance documents laying out FDA's position with respect to (1) manufacturer communications with payors, formulary committees, and similar entities, and (2) manufacturer communications consistent with FDA-required labeling. The payor guidance document was issued in response to a request from the Medical Information Working Group ("MIWG"), an ad hoc coalition of drug and device manufacturers co-represented by Ropes & Gray. Additionally, in response to comments received during a two-day public hearing held on November 9-10, 2016, FDA published a memorandum outlining the agency's current thinking with respect to the First Amendment implications of FDA's regulation of manufacturer communications about unapproved uses of approved or cleared medical products.

These documents represent a final attempt by the outgoing Administration to impact the agency's regulatory approach going forward. While it is possible that the new Administration will have different views on some or all of the positions FDA has set forth, particularly in the First Amendment memorandum, these documents represent long-awaited commentary on issues of critical importance to industry.

Draft Guidance on Payor Communications

The draft guidance document, entitled "Drug and Device Manufacturer Communications with Payors, Formulary Committees, and Similar Entities—Questions and Answers," addresses two types of manufacturer communications with payors. First, it addresses communication of healthcare economic information ("HCEI") about drug products to payors pursuant to Section 114 of the Food and Drug Modernization Act of 1997 ("FDAMA 114"), as amended by the 21st Century Cures Act. Second, and most significantly, it creates a new safe harbor for communications with payors about investigational drugs and devices.

1. Communication of HCEI Under FDAMA 114

Guidance on drug manufacturer communication of HCEI to payors has been long awaited by industry, which has sought clarification of FDAMA 114 since the statute was initially enacted in 1997. Under FDAMA 114, drug product manufacturers are permitted to communicate HCEI with certain audiences if such information is related to an approved indication and is supported by competent and reliable scientific evidence ("CARSE"). The draft guidance defines and clarifies key elements to qualify for the FDAMA 114 safe harbor, including (1) what information qualifies as HCEI; (2) the appropriate audience for the information; (3) when information "relates to an approved indication"; (4) the required level of evidentiary support; and (5) the disclosures that should accompany communications.

  • What Information Qualifies as HCEI? Under FDAMA 114, as amended by the 21st Century Cures Act, HCEI is defined as "any analysis (including the clinical data, inputs, clinical or other assumptions, methods, results, and other components underlying or comprising the analysis) that identifies, measures, or describes the economic consequences, which may be based on the separate or aggregated clinical consequences of the represented health outcomes, of the use of a drug." FDA's draft guidance clarifies that HCEI may include comparative analyses and may be presented in a variety of different formats (e.g., evidence dossier, reprint, or software model).
  • Who is the Appropriate Audience? Under FDAMA 114, as amended, HCEI may be communicated to "a payor, formulary committee, or other similar entity with knowledge and expertise in the area of health care economic analysis, carrying out its responsibilities for the selection of drugs for coverage or reimbursement[.]" In determining whether a particular audience qualifies under FDAMA 114, FDA's draft guidance clarifies that the agency will consider whether the entity (1) is constituted to consider HCEI and other information through a deliberative process, (2) has the appropriate range of knowledge to interpret HCEI, and (3) makes population-based decisions (as contrasted with the individual treatment decisions made by prescribers).
  • When Does Information "Relate to an Approved Indication"? Under FDAMA 114, as amended, HCEI must "relate to an [approved] indication." FDA's draft guidance clarifies that HCEI relates to an approved indication if it "relate[s] to the disease or condition, manifestation of the disease or condition, or symptoms associated with the disease or condition in the patient population for which the drug is indicated in the FDA-approved labeling." The draft guidance provides examples of such HCEI, including but not limited to data on long-term use, dosing regimens that vary from approved labeling, patient subgroups, and clinical outcome assessments.
  • What is the Required Level of Evidentiary Support? FDA's draft guidance interprets CARSE as meaning that HCEI should be "developed using generally-accepted scientific standards, appropriate for the information being conveyed, that yield accurate and reliable results." FDA indicates that it would look to research practices of authoritative bodies, such as the International Society for Pharmacoeconomic and Outcomes Research ("ISPOR") and the Patient-Centered Outcomes Research Institute ("PCORI"), for guidance on generally accepted scientific standards for HCEI. The draft guidance also clarifies that FDA intends to apply the CARSE standard to all components of HCEI, including inputs and assumptions related to both economic consequences and clinical outcomes.
  • What Disclosures Should Accompany HCEI? The draft guidance provides an extensive list of information that should be included when disseminating HCEI, including information on study design and methodology, generalizability, limitations, sensitivity analysis, and other material information. While many of these disclosures appear reasonable, others may be challenging from a practical standpoint or arguably go beyond the statutory requirement to include "a statement describing any material differences between the health care economic information and the [approved] labeling."

2. Communications Related to Investigational Products

In addition to clarifying the FDAMA 114 safe harbor, the draft guidance would create a new safe harbor for communications with payors about investigational products. Industry has previously called on FDA to clarify its policy in this area, given the critical importance of payors having access to information on pipeline products prior to approval or clearance to minimize coverage delays for patients.

The new safe harbor for communications about investigational products by definition would apply only to "drugs and devices that are not yet approved/cleared by FDA for any use (but which must be approved/cleared to be legally marketed)." It would not apply to communications related to investigational uses of approved or cleared products, which would presumably be limited to communication under other safe harbors (e.g., scientific exchange, responses to unsolicited requests, and dissemination of reprints).

In detailing the contours of the safe harbor, the draft guidance provides that FDA does not intend to object to communication of certain types of information about investigational products to payors, including but not limited to product information, factual presentations from clinical or preclinical studies, anticipated timeline for FDA approval/clearance, and product pricing information.

When communicating pre-approval information to payors, the draft guidance recommends that manufacturers include (1) a clear statement that the product is under investigation and that the safety or effectiveness of the product has not been established, and (2) information on the stage on product development. The draft guidance also suggests that manufacturers update payors if previously communicated information becomes outdated as a result of significant changes or new information about the investigational product (e.g., failure to meet primary efficacy endpoint in a phase 3 study).

Draft Guidance on Communications Consistent with FDA-Required Labeling

The second draft guidance document, entitled "Medical Product Communications That Are Consistent With the FDA-Required Labeling—Questions and Answers," addresses circumstances in which manufacturers may communicate information that is not contained in the required product labeling, but which is consistent with such labeling. The draft guidance explains that communication of information not contained in, but consistent with, FDA-required labeling will not alone be considered evidence of a new intended use. The draft guidance also affirms that FDA will not consider such information false or misleading merely because it is not supported by studies meeting the applicable approval standard for the product—i.e., for prescription drugs, the substantial evidence standard.

The draft guidance defines FDA-required labeling to mean the labeling reviewed and approved by FDA in a marketing application for a medical product (e.g., new drug application or a premarket approval application for a medical device). For products that do not require premarket approval, such as medical devices subject to premarket notification ("510(k)" clearance) or that are exempt from premarket notification, FDA states that required labeling includes the labeling relied on to provide adequate directions for use and other information required to appear in labeling.

The draft guidance outlines three factors for determining whether a communication is consistent with the FDA-required labeling and therefore will not be considered violative.

  • Conditions of Use. FDA states that the information in the communication relating to the product's conditions of use should be consistent with the FDA-required labeling for the product. FDA states that it would not consider a communication to be consistent with the required labeling if, for example, the communication represents the product for a different indication or patient population than reflected in the required labeling, or suggests conflicting information on limitations or directions for using the product, or its route of administration or strength.
  • Potential to Increase Risk of Harm. The draft guidance states that, if a communication alters the benefit-risk profile of a product in a way that may result in increased harm to health, this indicates that the communication is not consistent with the FDA-required labeling.
  • Ability to Use the Product Safely Under Required Labeling. The draft guidance states that, unless the directions for use in the FDA-required labeling enable the product to be used safely and effectively for the conditions suggested in the communication, the communication is not consistent with the FDA-required labeling.

FDA also provides examples of information that would and would not be considered consistent with the required labeling. Information consistent with the required labeling may include, for example, comparative information based on "a" head-to-head study with another medical product approved/cleared for the same indication (raising the question of whether FDA is abandoning the standard of two head-to-head studies for drug comparative claims), information on long-term safety or efficacy of products approved/cleared for chronic use, information on effects in a patient subgroup included within the approved/cleared patient population, or additional context on the product's mechanism of action described in the FDA-required labeling. Examples of information that would not be consistent with the FDA-required labeling include information on a different disease or condition, patients outside the approved/cleared patient population, a different disease stage or severity, or dosages or dosage forms that differ from the FDA-required labeling.

In addition to addressing consistency with FDA-approved labeling, the draft guidance outlines criteria for evaluating whether a communication may be considered false or misleading. FDA states that any data, studies, or analyses relied on should be "scientifically appropriate and statistically sound to support the representations or suggestions made in the communication." In addition, FDA states that the information must be presented in a truthful and non-misleading manner, with appropriate disclosures and contextual information.

Although FDA's drug regulations have long permitted manufacturers to disseminate some promotional information "consistent with" but not the same as the FDA-required labeling, the draft guidance represents the first time FDA has provided detailed guidance on how it assesses consistency with the approved labeling. The draft guidance also addresses medical devices in addition to drugs, which may be helpful to device manufacturers given the relative lack of device-specific rules or guidance in this area.

First Amendment Memorandum

As discussed in a previous Ropes & Gray Alert, FDA held a two-day public hearing relating to FDA's regulation of off-label communications on November 9-10, 2016. Ropes & Gray partner Kellie Combs (Washington, D.C.) testified at the hearing on behalf of MIWG, expressing concern that FDA had "fail[ed] to address or even mention First and Fifth Amendment dictates." FDA recently acknowledged the concern that it "had not sufficiently discussed the First Amendment in the notice of the public hearing," and published a memorandum entitled "Public Health Interests and First Amendment Considerations Related to Manufacturer Communications Regarding Unapproved Uses of Approved or Cleared Medical Products."

The memorandum reaffirms and seeks to bolster the basis for FDA's long-standing restrictions on manufacturer speech regarding unapproved uses of medical products. It focuses on explaining the public health interests served by the agency's current regulatory approach, describes harms associated with false or misleading off-label promotion, and asserts that various alternative approaches that have been proposed would be inadequate. In response, industry is likely to argue that the memorandum downplays the public health benefits of off-label use, instead stressing isolated historical examples of harm from unapproved uses, and inadequately considers the impact of recent court decisions challenging FDA's regulatory framework on First Amendment grounds, including United States v. Caronia, 703 F.3d 149 (2d Cir. 2012) and Amarin Pharma v. FDA, 119 F. Supp. 3d 196 (S.D.N.Y. 2015). It remains to be seen whether, under the new Administration, FDA will continue to advance the arguments set forth in the memorandum.

FDA will accept comments to the two draft guidance documents and First Amendment memorandum until April 19, 2017.

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
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 you may opt out by clicking here

    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.

    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.

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