Premarket Review: Laboratory Developed Tests FAQs
Predicate Devices
A: A predicate device for purposes of FDA clearance of a 510(k) submission is a "legally marketed device." A legally marketed device is a device that has been approved or cleared by FDA, or that was legally marketed prior to May 28, 1976 (preamendments device) and for which a PMA is not required. The final rule does not change this requirement.
FDA Review
A: FDA reviews submissions according to the premarket review timelines negotiated with industry in connection with MDUFA reauthorization, regardless of the submitter. The FDA notes that its premarket review timelines are negotiated with industry in connection with MDUFA reauthorization.
As noted in the current MDUFA V commitment letter, "To the extent that laboratories make submissions regarding LDTs that are covered by the MDUFA V agreement, FDA will treat such LDT submissions no less favorably than other submissions to which MDUFA V performance goals apply."
A: As discussed during the webinar, the Medical Device User Fee Amendments, also called MDUFA, authorizes the FDA to collect user fees for the process for the review of medical devices. The user fee program is negotiated with regulated industry every five years. At the end of these negotiations, FDA commits to specific performance goals and program enhancements and Industry commits to providing resources through user fees to support them. This includes goals for FDA to perform our reviews in a specific period of time, with the length of time varying based on the type of submission.
During the current MDUFA V program, FDA aims to complete review of a 510(k) submission within 90 days. For a De Novo submission, FDA aims to complete review within 150 days. And for PMAs, the goal review time is 180 days. If a file is placed on hold, where the FDA has requested additional information from the manufacturer, the time the file is on hold does not count toward the FDA review time, though it does count towards the FDA and Industry's shared outcome goals, referred to as "total time to decision".
MDUFA V began in 2022 and expires on September 30, 2027. This is before FDA expects compliance with pre-market review requirements for IVDs offered as LDTs under the phaseout policy described in the preamble to the LDT Final Rule. We expect that MDUFA VI will be negotiated and authorized before that time.
As noted in the current MDUFA V commitment letter, "To the extent that laboratories make submissions regarding LDTs that are covered by the MDUFA V agreement, FDA will treat such LDT submissions no less favorably than other submissions to which MDUFA V performance goals apply."
More information on user fee agreements can be found on FDA's website.
Submissions
A: Most often, a single submission will contain only a single device with a single indication for use. However, as described in the FDA guidance "Bundling Multiple Devices or Multiple Indications in a Single Submission" there are instances where it may be appropriate to combine information supporting multiple devices or multiple indications for use in a single submission. Generally, this occurs when the devices or indications present scientific and regulatory issues that can most efficiently be addressed during one review. In determining whether it can review a bundled submission during the course of one review, FDA may consider whether:
- the supporting data are similar;
- primarily one review division/group will be involved; and
- the devices or indications for use are similar.
An example of a multianalyte panel that would be appropriate for a single submission would be a panel of general chemistry analytes, all intended for use on the same clinical chemistry analyzer, and all intended for use in the same patient population. For example, a multianalyte panel including sodium, potassium, and calcium could be submitted as a single submission. Similarly, we have received submissions for a panel of respiratory viruses, such as influenza A, influenza B, and RSV, and drugs of abuse panels that include cocaine, THC, opiates, methamphetamine, amphetamine, etc., in a single submission.
An example of a multianalyte panel that would not be appropriate for a single submission would include a panel with different analytes and with different intended uses that are supported by different types of data. For example, a test to assess risk of developing type 2 diabetes in a population of patients who are overweight but otherwise healthy and a test to assess risk of kidney failure in patients who have already been diagnosed with moderate kidney disease would not be appropriate for bundling into a single submission.
User fees are based on the submission type (i.e., 510(k), De Novo, PMA), and are not dependent on the number of analytes or indications included in that submission.
A: The "fast-track" submission program applies specifically to the review of new drugs and biological drug products, as described in the 2014 Expedited Programs for Serious Conditions – Drugs and Biologics Guidance. However, FDA's Breakthrough Devices program is intended to help expedite the development and review of certain devices that provide for more effective treatment or diagnosis of life-threatening or irreversibly debilitating diseases or conditions (21 U.S.C. 360e-3). Submissions for IVDs designated as Breakthrough Devices receive priority review. More information about the Breakthrough Devices Program, including a link to the Breakthrough Devices Program final guidance, can be found on the FDA website: Breakthrough Devices Program | FDA.