FDA Finalizes CLIA Waiver Guidance for Approval of New In Vitro Diagnostic Devices

On Feb. 25, the FDA issued a pair of final guidances to help manufacturers seeking clearance for new in vitro diagnostic devices. Here is a summary of the key points from each guidance.

CLIA Waivers

The first guidance document, “Recommendations for CLIA Waiver Applications for Manufacturers of In Vitro Diagnostic Devices,” explains how sponsors can demonstrate accuracy, i.e., “insignificant risk of erroneous result,” of in vitro diagnostic tests for purposes of obtaining a CLIA waiver. Among other things, it recommends that sponsors use a two-tier approach to demonstrate that their device is robust and has appropriate and effective risk control measures to ensure insignificant risk of an erroneous result:

• Tier 1: Risk Analysis and Flex Studies. Sponsors should conduct a systematic and comprehensive risk analysis identifying all potential sources of error, including test system failures and operator errors, and which of these errors can lead to a risk of a hazardous situation; and
• Tier 2: Fail-Safe and Failure Alert Mechanisms. Sponsors should also identify the control measures, including fail-safe and failure alert mechanisms that will reduce risks for each of the sources of error they identify. Then, once the control measures have been implemented, they should (1) verify that each control measure has been properly implemented, and (2) verify and/or validate the effectiveness of each control measure.

Dual 510(k) and CLIA Waiver Submissions

The second guidance document, “Recommendations for Dual 510(k) and CLIA Waiver by Application Studies,” aims to make the dual CLIA waiver and Section 510(k) clearance pathway for certain Class I and Class II IVD devices created as part of the Medical Device Use Fee Amendment of 2012 less burdensome. For dual submission, the guidance recommends that sponsors include:

• A device description;
• A determination that a device is simple to use;
• Results of a risk analysis with potential sources of error identified;
• Failure-alert and fail-safe mechanisms that have been verified to mitigate risk of errors;
• Flex studies demonstrating insensitivity of the test to environmental and usage variations under stress conditions;
• Descriptions of the design;
• Results of analytical studies testing sensitivity, measuring interval, specificity, linearity, precision, carry-over, reagent stability and sample stability;
• Comparison studies and reproducibility studies;
• Clinical performance studies, if necessary; and
• Proposed device labeling.

New FDA Approvals

Key new product approvals announced from mid-February 2020 through March 20, 2020 include emergency use authorization (EUA) for eight different commercial tests for qualitative detection of the SARS-CoV-2 virus in patients showing symptoms or suspected of having coronavirus: