The US Food and Drug Administration (FDA) reissued two draft guidances on Wednesday to help in vitro diagnostic (IVD) manufacturers apply for and obtain Clinical Laboratory Improvement Amendments (CLIA) waivers.
The newly drafted guidance documents—first issued
last November—were updated to reflect input from the comment period that closed after an extension granted per the request of the Coalition for CLIA Waiver Reform earlier this year.
Modifications to the 2017 draft policies include a rewritten section in the overarching recommendations for IVD manufacturers seeking CLIA waivers and revamped policies on the dual 510(k) clearance and CLIA waiver pathway. The new draft guidance on 510(k)-CLIA waiver polices was condensed to just 12 pages vs. the 49 pages in the previous version, though the latter also include several nixed appendices.
FDA’s Center for Devices and Radiological Health (CDRH) chose to redraft the policies in the form of new draft guidance to welcome any additional comments for further policy modifications, if appropriate.
The new 14-page draft guidance on recommendations for CLIA waiver applications will replace the 2017 “select updates” to the 39-page guidance finalized in 2008 as outlined in section V on demonstrating “an insignificant risk of an erroneous result.” Firms are required to demonstrate the unlikelihood of erroneous results and unreasonable risk of harm to obtain a certificate of waiver (CW), which is essentially CDRH’s OK for a laboratory to perform clinical studies on IVDs of low complexity indicated for home use or for over-the-counter use.
The revised version of section V in the “select updates” draft guidance increases the number of recommended study design routes when seeking CLIA waivers for candidate tests from two in 2017 to four new options, including three comparison study designs and an alternative for certain test systems.
The four options were initially set forth in a joint proposal from AdvaMed’s IVD division and the Coalition for CLIA Waiver Reform, submitted to CDRH during the open comment period. These relate to test performance in the hands of trained users, study designs modeled after FDA guidance on assay migration studies for IVD devices as well as use of an “appropriate comparative method” to demonstrate accuracy of a candidate test in the hands of untrained operators. The third option is limited to certain test system scenarios, including “intended use patient populations are sufficiently familiar.”
“While our proposal recommendations were aimed at the section V guidance and specific requirements for CLIA waiver applications, we note that they would apply in the case where a submitter seeks a sequential, or stepwise, 510(k) clearance followed by CLIA waiver approval,” Khatereh Calleja, senior vice president of technology and regulatory affairs at AdvaMed, wrote in a submitted comment.
Updated recommendations in the 12-page 510(k)-CLIA waiver draft guidance cover the process and content of a dual submission and general considerations for both comparison and reproducibility study designs. CDRH said it “believes that increased use of this pathway will speed up the process of bringing simple and accurate IVD devices to CLIA waived settings, which will better serve patients and providers.”
Select Updates for Recommendations 1 1 2 for Clinical Laboratory Improvement 3 Amendments of 1988 (CLIA) Waiver 4 Applications for Manufacturers of 5 In Vitro Diagnostic Devices: Draft Guidance
Recommendations for Dual 510(k) and CLIA Waiver by Application Studies: Draft Guidance