FDA Provides Some Clarity to Complex Regulatory Environment for Molecular Diagnostics

Posted 10 November 2014 By Alexander Gaffney, RAC


A new guidance document issued by the US Food and Drug Administration's (FDA) Center for Devices and Radiological Health (CDRH) aims to clarify the regulatory processes by which certain molecular diagnostic devices are approved or cleared by federal regulators.


As FDA explains in its guidance document, Molecular Diagnostic Instruments With Combined Functions, molecular diagnostic instruments are "critical components of certain in vitro diagnostic devices (IVDs)."

"These types of instruments are not generally approved/cleared alone, i.e., without an accompanying assay, because their safety and effectiveness or substantial equivalence cannot be evaluated without reference to the assays they run and the assay's defined performance parameters," FDA continued. "The same instruments may also be used for additional purposes that do not require FDA approval or clearance, such as for basic scientific research-purposes this document refers to as functions for which approval/clearance is not required."

Such uses most notably include lab-developed tests (LDTs), which historically have not been cleared or approved for use by FDA.

The problem, FDA says, is that because some devices can have a multitude of claims and uses—some approved by FDA and some not—companies frequently solicit the agency for advice regarding "the permissibility of having functions for which approval/clearance is not required on an instrument intended to be used with approved/cleared in vitro diagnostic assays."

In other words, does a company need to separately market the devices' applications, or may a single device have the full information, including the approved and unapproved labeling?

Guidance Details

FDA's final guidance indicates that no, companies may not market a single device using a single label containing both approved and unapproved uses. However, FDA said it will permit molecular diagnostic instruments that have both approved/cleared functions as well as "additional functions for which the sponsor need not seek approval or clearance" to be marketed so long as there are certain controls in place.

For example, devices will need to be able to assure that the unapproved/uncleared functions of the devices do not "interfere with or adversely affect the safety or effectiveness of the approved/cleared functions.” Similarly, controls will need to be in place to ensure that end users cannot confuse the FDA-sanctioned uses of the device and those unsanctioned by FDA.

FDA offers five potential control measures which companies may use, including the use of clearly marked "result reports," the implementation of a risk mitigation plan tailored to the devices' use, clear and separate labeling for the devices' use, software controls on the device (i.e. a "dual-boot" design), and validation procedures.

If FDA deems those control measures to be sufficient, it is likely to approve or clear the device, it says in its guidance. As for the review of functions not required to be cleared or approved by FDA, the agency says it will only do so "for the purpose of evaluating the risks posed to the approved/cleared functions and adequacy of the device."

Notably, FDA will also require the manufacturer of the device to report all device-related adverse events through FDA's Medical Device Reporting (MDR) system regardless of whether the malfunction is for a purpose approved or cleared by FDA. "All instrument device functions, whether approved/cleared or not required to be approved/cleared can have a direct or indirect adverse impact on approved/cleared indications," the agency explained.

Also notable is FDA's advocacy for a "dual-boot" design to be used in many devices. "When using dual-boot design, at start-up the instrument gives a choice of either the approved/cleared functions or functions for which approval/clearance is not required, requiring the user to choose one or the other depending on the type of assay to be performed," FDA explained. "The user would not be able to switch between functions without first going back to the start-up screen," thereby separating the functions of the device and preventing any user confusion, FDA added.


Molecular Diagnostic Instruments With Combined Functions (FR)

Share this article:

Categories: In vitro diagnostics, Medical Devices, Submission and registration, News, US, CDRH

Tags: Molecular Diagnostic Instruments, Guidance, Final Guidance, Molecular Diagnostics, IVDs

Regulatory Exchange: Latest Updates From the Community