United States: FDA Notifies Congress Of Framework For Long-Awaited Guidance On Laboratory Developed Tests And Issues Final Guidance On Companion Diagnostics

Last Updated: August 26 2014
Article by Linda Bentley

Laboratory Developed Tests

After many years of promising that it would be providing guidance on the regulation of laboratory developed tests (LDTs), the Food and Drug Administration (FDA) provided notice to Congress on July 31, 2014 that it intends to issue a draft guidance document entitled, "Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs)" and an accompanying draft guidance document entitled, "FDA Notification and Medical Device Reporting for Laboratory Developed Tests (LDTs)." The notice, which may be found here, includes the anticipated details of the draft guidance documents ("Draft Guidance").1

The FDA has consistently claimed that it has the authority to regulate LDTs, which it defines as in vitro diagnostic tests (IVDs) intended for clinical use and designed, manufactured and used within a single laboratory, as medical devices. As long as the single laboratory was a laboratory certified under the Clinical Laboratory Improvement Amendments (CLIA), however, the FDA generally exercised enforcement discretion in not otherwise regulating most LDTs. For a variety of reasons, including the increasing growth of personalized medicine and the introduction of technological advances that have enabled the use of IVDs in guiding critical patient care decisions, the FDA has decided that additional and more consistent and predictable regulatory oversight is necessary.

In the Draft Guidance, the FDA describes its proposed regulatory framework as a phased-in risk-based approach to the regulation of LDTs in a manner that is consistent with the FDA's current regulation of IVDs. This means that new LDTs could be subject to requirements for premarket review of higher-risk LDTs that have the same intended uses as IVDs that were (i) cleared for marketing by the FDA under section 510(k) of the Food, Drug and Cosmetic Act, or (ii) approved for marketing after submission, review and FDA approval of a premarket approval application, or PMA.2

For high-risk or Class III devices, the FDA has indicated that registration and listing requirements (with a notice option) and adverse event reporting will begin 6 months after the Draft Guidance is finalized with premarket review requirements (PMAs for Class III devices) beginning 12 months after the Draft Guidance is finalized for the highest risk devices. A 4-year phase-in will apply to the remaining high-risk devices. Devices that are already on the market would be allowed to remain on the market during FDA's review and consideration of applications. The FDA's initial focus will likely be on (i) LDTs that act like already cleared or approved companion diagnostics, (ii) LDTs with the same intended use as an FDA-approved Class III medical device, and (iii) certain LDTs for determining the safety or efficacy of blood or blood products.

For moderate-risk or Class II devices, FDA registration and listing requirements (with a notice option) and adverse event reporting will begin 6 months after the Draft Guidance is finalized. Premarket notice requirements (510(k)s for Class II devices) will begin after the high-risk LDTs are completed (or 5 years after the Draft Guidance is finalized) with a 4-year phase in.

There will be a 12-month phase-in period for LDTs on the market at the time that the Draft Guidance is finalized which may be extended if an appropriate premarket application is made during that period.

For some manufacturers of LDTs, notification to FDA that they are developing LDTs 6 months after the Draft Guidance becomes finalized may take the place of registration and listing, although they will still be required to begin reporting significant adverse events.

The FDA will continue to exercise enforcement discretion for LDTs used solely for forensic purposes, certain LDTs for transplantation, low-risk LDTs, as well as LDTs intended for rare diseases and unmet needs where there is no FDA-cleared or approved alternative. However, the FDA may require compliance with certain non-review requirements such as registration, listing and adverse event reporting.

Additional details regarding the proposed framework for regulation and procedural and timing information are provided in the Draft Guidance and will be helpful for planning purposes, but the Draft Guidance will not be considered "issued" until at least 60 days after the July 31, 2014 notice to Congress. Although FDA received comments on its anticipated guidance for many years preceding the notice to Congress, it will consider additional comments for some period of time before the Draft Guidance is finalized.3 Also, as is the case with all guidance documents, the final guidance will be a statement of the FDA's thinking on a particular topic and recommendations at the time that it is issued, and does not create or confer any rights nor bind the FDA. Alternative approaches may be used if they satisfy the applicable law and regulations.

Companion Diagnostics

On the same day the FDA provided notice regarding its intended LDT regulatory framework, it also issued a final guidance document entitled, "In-Vitro Companion Diagnostic Devices" (the Guidance). The Guidance, dated August 6, 2014, found here, made few revisions to the draft guidance which was issued 3 years earlier. The Guidance is intended to assist companies developing in vitro companion diagnostic devices (IVD Companion Diagnostics) and companies developing therapeutic products that depend on the use of a specific IVD Companion Diagnostic for the safe and effective use of the therapeutic product.

The FDA defines an IVD Companion Diagnostic as a device that provides information that is essential for the safe and effective use of a corresponding therapeutic product. If the FDA determines that an IVD Companion Diagnostic is essential to the safe and effective use of a new drug or a new indication for an already approved drug, it will not approve the new drug or the new indication unless the IVD Companion Diagnostic is also cleared or approved for that indication. The FDA expects that the therapeutic sponsor will address the need for an approved (PMA) or cleared (510(k)) IVD Companion Diagnostic in its product development plan in most cases, but recognizes that there are certain situations in which contemporaneous clearance or approval of the drug and IVD Companion Diagnostic may not be possible.

The FDA had already approved 18 IVD Companion Diagnostics, all of which were linked to cancer drugs, as of the date of the Guidance, and it encourages sponsors of IVD Companion Diagnostics and the related therapeutic drugs to meet early with the relevant review divisions at the FDA to solicit pre-submission feedback.


1 The Food and Drug Administration Safety and Innovation Act of 2012 (FDASIA) required the FDA to provide Congress with at least 60 days' notice of its intent to issue draft guidance on the regulation of LDTs.

2 The FDA acknowledged that many tests being marketed as LDTs don't meet its definition of an LDT and therefore are out of compliance with the Food Drug and Cosmetic Act. Nevertheless, it intends to apply the same risk-based approach set forth in the Guidance Documents to any IVD being offered as an LDT by a CLIA laboratory.

3 The FDA has on occasion published draft guidance documents that have never been finalized.

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.

Linda Bentley
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
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
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.


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