United States: FDA Issues Draft Guidance Regarding Waiver Of Single Shared System REMS Requirement

Last Updated: June 14 2018
Article by Ropes & Gray LLP's FDA Regulatory Practice

FDA Commissioner Scott Gottlieb has vowed to take steps to speed the review and approval of generic drugs as part of his overall priority to address concerns about drug prices. While FDA has very limited authority regarding drug pricing, Commissioner Gottlieb has pushed to encourage generic competition and has sought to address regulatory issues that he believes could be impediments to that competition. To that end, Commissioner Gottlieb has cited the statutory provision requiring a single, shared system ("SSS") for a risk evaluation and mitigation strategy ("REMS") with elements to ensure safe use ("ETASU") as a potential obstacle in the way of generic drug approval. Pending legislation, discussed more fully below, may clarify FDA's ability to move away from the statutory preference for the SSS REMS. In the meantime, however, on May 31, 2018, FDA issued draft guidance regarding the waiver of the SSS REMS requirement that (1) largely replicates what is already in the statute; (2) sets forth the agency's current standards and processes for assessing a waiver application; and (3) implies that FDA may be interested in granting more waivers going forward.

Statutory Background

Section 505-1 of the Federal Food, Drug, and Cosmetic Act ("FD&C Act") authorizes FDA to require a REMS if FDA determines that a REMS is necessary to ensure that the benefits of a drug outweigh its risks. Examples of such REMS include medication guides that provide risk information to patients, communication plans for health care providers, and/or ETASU, when such elements are necessary for risk mitigation. ETASU may include such elements as training for health care providers or monitoring of patients. REMS generally involve a timetable of submission of assessments of the strategy, and may include an ETASU implementation system.

Section 505-1(i)(1)(B) of the FD&C Act requires abbreviated new drug application ("ANDA") applicants referencing a drug with a REMS with ETASU to use an SSS, unless otherwise waived. However, FDA is authorized by statute to grant a waiver of the SSS requirement and permit the ANDA applicant to use a "different, comparable aspect" of the ETASU. Such waivers have been granted by FDA three times. Section 505-1(i)(B) expressly allows for waiver of the SSS requirement in two situations. FDA may grant a waiver if it finds that, pursuant to section 505-1(i)(B)(i), the burden of creating an SSS outweighs the benefits of a single system. FDA may also grant a waiver if, pursuant to section 505-1(i)(B)(ii), an aspect of the ETASU is claimed by an unexpired patent or is a method or process that is entitled to protection as a trade secret, and the ANDA applicant certifies that it sought a license for use of the aspect, but was unable to obtain one.

Draft Guidance

FDA's draft guidance seeks to clarify the agency's policy on SSS REMS waiver requests, but is limited to waivers of the SSS requirement where there is no previously established SSS and no previously approved separate REMS for ANDA(s) that the application can join.

The draft guidance primarily addresses waivers pursuant to section 505-1(i)(1)(B)(i). According to the draft guidance, in order to determine whether a waiver is appropriate, FDA will compare the benefits of an SSS compared to the burden, taking into account the impact on health care providers, patients, ANDA applicant(s), and the reference listed drug ("RLD") holder. Some of the benefits contemplated by FDA include increased efficiency and potential for sharing costs between ANDA applicants and RLD holders, as well as shared infrastructure for health care providers. With respect to the burdens involved in forming an SSS, the draft guidance notes that development of an SSS REMS ordinarily involves negotiations and/or agreements between companies that are often competitors and potential adversaries in patent litigation. Additionally, formation of an SSS REMS may be time-consuming and complicated, which may create a delay in access to generic versions of drugs for health care providers and patients.

The draft guidance notes that, while FDA generally notifies an ANDA applicant of a SSS REMS requirement after the ANDA has been received for review, FDA will consider a waiver request at any time. An ANDA applicant may either submit an SSS REMS, or a proposed separate REMS with request for waiver. Regardless of whether the applicant submits an SSS REMS or a proposed separate REMS, FDA will then review the application and recommend that the proposed REMS be submitted to FDA by the midpoint of the pending application review cycle to allow for sufficient time for review. Although a waiver request is not required, FDA encourages the submission of a written waiver request to facilitate its review of the application. The draft guidance instructs ANDA applicants to include a discussion and analysis of the benefits and burdens of having an SSS, as well as a description of the proposed separate program and a description of how aspects of the required ETASU are comparable to those of the RLD REMS. Once a waiver is submitted, FDA will conduct a case-specific analysis for a proposed separate REMS. FDA states that a separate system for ETASU with a waiver of the SSS requirement must include the same ETASU as described in the statute. By detailing the process and standards, the draft guidance appears to provide a roadmap for ANDA applicants seeking to obtain a waiver.

In furtherance of transparency in this area, FDA also issued a second guidance document on May 31, 2018, that describes general principles and recommendations to assist sponsors with developing SSS REMS programs. This draft guidance provides recommendations on the development of an SSS REMS for multiple prescription drug products and discusses benefits of an SSS REMS. FDA outlines situations where it will require or recommend SSS REMS, suggests formation of industry working groups ("IWGs"), and outlines its role in the development of REMS. Notably, FDA does not advise on business arrangements being negotiated, nor arbitrate substantive disputes about terms of contract; instead, its role is limited to setting expectations and "facilitat[ing] collaborations" throughout the process, if necessary. The draft guidance also provides links to resources for industry in preparing REMS submissions, and an outline of timing for REMS applications.

Pending Legislation

In April 2017, Senator Patrick Leahy introduced the Creating and Restoring Equal Access to Equivalent Samples Act of 2017 ("CREATES Act") that includes provisions to address the SSS REMS requirement and waiver authority. At this time, press reports indicate there are still ongoing negotiations regarding the CREATES Act, but it is unclear if it will be considered or enacted by this Congress. The sponsors of the CREATES Act claim that it is essential for developers of generic drugs to be able to join the RLD manufacturers (also known as "license holders" within the statute) in an SSS of ETASU, and that certain license holders are preventing generic drug developers from doing so through the REMS requirement. Those sponsors assert that antitrust laws are insufficient and that a "more tailored legal pathway" is necessary to ensure competition in the drug and biological products marketplace, and call for "clearer regulatory authority" with respect to the FDA's ability to waive the SSS requirement. In addition to providing a clearer avenue for SSS waivers, the legislative proposal also allows generic drug providers to bring suit against license holders for failure to provide sufficient quantities of a covered product. If the proposals outlined in the CREATES Act are enacted into law, they will supersede the provisions of the draft guidance on waiver of the SSS REMS requirement.

FDA will accept comments on both draft guidance documents until July 31, 2018.

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.

Similar Articles
Relevancy Powered by MondaqAI
McDermott Will & Emery
In association with
Related Topics
Similar Articles
Relevancy Powered by MondaqAI
McDermott Will & Emery
Related Articles
Related Video
Up-coming Events Search
Font Size:
Mondaq on Twitter
Mondaq Free Registration
Gain access to Mondaq global archive of over 375,000 articles covering 200 countries with a personalised News Alert and automatic login on this device.
Mondaq News Alert (some suggested topics and region)
Select Topics
Registration (please 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.


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.


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