FDA Dual 510(k) and CLIA Waiver Guidance

01 What the document says

Manufacturers of tests meant for waived settings traditionally cleared the device first, then ran a second set of studies to obtain a CLIA waiver. The Dual 510(k) and CLIA Waiver by Application pathway lets a sponsor file both at once, and this guidance explains how to design the comparison and reproducibility studies so that one data set satisfies both reviews. FDA describes the pathway as optional but, in many cases, the least burdensome and fastest route for a new IVD intended for waived use.

The central idea is that the comparison study and the reproducibility study required in a 510(k) can be performed by untrained operators in waived-type settings rather than by laboratory-trained operators. When they are, the same results demonstrate substantial equivalence for the 510(k) and accuracy in the hands of intended users for the waiver. The guidance walks through how to structure the comparison study (prospective enrollment of the intended-use population at representative sites, comparison to an appropriate reference method or cleared predicate, analysis in the categories relevant to the intended use) and the reproducibility study (multiple sites, multiple operators, multiple days, with a sample panel spanning the decision thresholds).

It also describes the remaining elements each submission needs on its own: the 510(k) still requires analytical studies such as limit of detection, precision, interference, and cross-reactivity, and the waiver application still requires the device description, risk analysis, and flex studies described in the companion CLIA waiver guidance. A sponsor can request FDA feedback on the combined protocol through a Pre-Submission before enrolling.

02 What it means when you plan a study

• One prospective clinical study, run by untrained operators at waived-type sites, replaces two sequential studies; the saving is mostly calendar time and a second round of site contracting and IRB review.
• Because the same operators generate the 510(k) data, the usual 510(k) fallback of trained-operator testing is not available; any operator-driven failure in the field counts against both submissions at once.
• The reproducibility study has to be planned as a multi-site, multi-operator, multi-day design with untrained operators and a panel that brackets the cutoffs, which means more coordination than a single-laboratory precision study.
• Sample size is set by the stricter of the two reviews: enough positives and negatives in each category for substantial equivalence, and enough to show accuracy for waiver at every site, so plan for prevalence-driven enrollment and possibly enrichment with archived specimens where the guidance allows it.
• A Pre-Submission on the combined protocol is strongly worth the weeks it takes, because the two review divisions must agree on the single design before data are collected.

03 Pathways it applies to

• 510(k) Clinical Studies
• CLIA Waiver Studies
• Dual Submission Studies

Source document: Recommendations for Dual 510(k) and CLIA Waiver by Application Studies (fda.gov).