EMERGO SUMMARY OF KEY POINTS:

• New FDA recommendations issued for IVD manufacturers using the Dual 510(k) and CLIA Waiver by Application registration pathway.
• The FDA’s Dual Submission pathway allows IVDs to reach the US market faster than if registrants obtain 510(k) clearance and then CLIA waived categorization in a stepwise process.
• The Dual Submission registration pathway is best suited for simple IVDs  subject to 510(k) rather than Premarket Approval (PMA) review.

New guidance from the US Food and Drug Administration explains requirements for in vitro diagnostic manufacturers to register for premarket notification using the agency’s Dual 510(k) and Clinical Laboratory Improvement Amendments (CLIA) Waiver by Application.

The draft guidance notes that the dual pathway allows manufacturers of new IVD devices faster US market access by obtaining 510(k) clearance alongside CLIA waived categorization, which would otherwise occur after premarket notification or approval of an IVD in what the agency calls a “stepwise approach.” CLIA requirements, covered in separate guidance, apply to FDA categorization of IVD products according to their complexity.

What constitutes a Dual Submission?

According to the guidance, Dual Submissions are most appropriate for IVDs with the following characteristics:

• Simple
• Include fail-safe and failure alert features
• Have few or no pre-analytical steps
• Subject to 510(k) rather than Premarket Approval review

FDA recommends that an IVD registrant first request a Pre-Submission (Pre-Sub) meeting in order to inform the agency that it plans to submit a Dual Submission. Then, the registrant should include the following components in the Dual Submission itself:

• IVD device description showing that it is demonstrably simple according to criteria listed in Section III of FDA CLIA Waiver Application guidance
• Risk analysis results of the device that identify potential sources of error
• Description of device’s failure-alert and fail-safe mechanisms, including validation and verification studies showing effectiveness of these measures
• Results of flex studies demonstrating effectiveness of the device under stress conditions
• Analytical study results covering sensitivity and specificity, measuring intervals, linearity and related issues
• Design and results of comparison studies showing insignificant risk of the device’s use by untrained operators
• Design and results of reproducibility studies of the device carried out by untrained operators
• Proposed device labeling and instructions for use

Dual Submission registrants should also include appropriate 510(k) documents in their applications.

Dual Submission study recommendations

The guidance also recommends that Dual Submission applicants design comparison and reproducibility studies that closely replicate CLIA waived patient samples and environments. Study designs should identify CLIA Waiver testing sites, untrained operators and intended sample types and matrices.

Related US FDA regulatory resources from Emergo:

• FDA 510(k) premarket notification consulting for medical device and IVD companies
• FDA Pre-Submission (Pre-Sub) consulting support
• Whitepaper: US FDA 510(k) submission preparation