FDA Issues Two Guidances on CLIA Waiver Applications, 510(k) Dual Submissions

Regulatory NewsRegulatory News | 28 November 2017 |  By 

The US Food and Drug Administration (FDA) on Tuesday issued two draft guidances aimed at updating its recommendations for in vitro diagnostics (IVDs) seeking a waiver from requirements under the Clinical Laboratories Improvement Amendments (CLIA) in line with provisions of the 21st Century Cures Act and the recently reauthorized Medical Device User Fee Amendments (MDUFA IV).

Under CLIA, clinical laboratories must obtain a certificate to perform complex diagnostic tests, or a waiver from CLIA requirements to perform tests that have "an insignificant risk of an erroneous result." Such tests include ones that have been approved by FDA for home use or are so simple and accurate that the likelihood of an erroneous result is negligible.

When FDA clears or approves IVDs it categorizes the tests as either waived, of moderate complexity or high complexity. Tests that are categorized as waived can be performed by laboratories with a CLIA waiver, while laboratories must have a CLIA certificate to perform moderate and high complexity tests. IVD makers can also request that FDA re-categorize moderate complexity tests as waived through FDA's CLIA waiver by application pathway.

Demonstrating Accuracy

The first of the two draft guidances details proposed updates to FDA's 2008 guidance on CLIA waiver applications for demonstrating accuracy as required under Cures, which called on FDA to provide recommendations on demonstrating comparable performance between a waived test user and a "moderately complex laboratory user."

For the time being, FDA says IVD makers should follow the recommendations for demonstrating accuracy in the 2008 guidance. However, once the draft guidance is finalized, FDA says it will replace the section on accuracy in the 2008 guidance with the new recommendations.

According to FDA, the changes introduced in the new draft guidance provide "additional details and pathways for demonstrating that a test has an insignificant risk of erroneous result[s]."

Dual 510(k) and CLIA Waiver by Application Studies

The second guidance provides recommendations on the studies IVD makers should conduct to support both 510(k) clearance and CLIA waiver by application submissions.

Under MDUFA III, FDA established a dual submission pathway for 510(k) and CLIA waivers that allows IVD makers to conduct a single set of comparison and reproducibility studies with untrained test operators to satisfy both types of submission.

Under MDUFA IV, industry committed that applicants would inform FDA of their intent to submit a dual 510(k) and CLIA waiver during the pre-submission process.

FDA says it believes the dual submission pathway represents the least burdensome approach for many new IVDs that are likely to be categorized as moderate risk and can provide cost savings for IVD makers by allowing them to streamline their development program.

While FDA notes that both types of submissions contain a number of different components, both require comparison and reproducibility studies that can be streamlined to fulfill requirements for both submissions.

In general, FDA says it recommends that IVD makers include the following in their dual submissions:

  • Device description and determination that the device is "simple"
  • Risk analysis
  • Failure-alert and fail-safe mechanisms
  • Flex studies
  • Analytical studies
  • Comparison study
  • Reproducibility study
  • Labeling

The agency also notes that because dual submissions include a complete 510(k), its formatting requirements, refuse to accept policy and any applicable device-specific guidance still apply.

Recommendations for Dual 510(k) and CLIA Waiver by Application Studies, Federal Register Notice

Select Updates for Recommendations for Clinical Laboratory Improvement Amendments of 1988 (CLIA) Waiver Applications for Manufacturers of In Vitro Diagnostic Devices, Federal Register Notice


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