Table 5.

Elements for liquid biopsy regulatory submissions

Tools	Characteristics
Single‐site approvals	Simplify regulatory review and approval for liquid biopsy diagnostics, which cannot be submitted for approval with FDA‐cleared instruments. Strategic decision early in development. Instinctive for product evolution from a CLIA laboratory to FDA approval.
Narrow contexts of use	Narrow clinical phenotype for populations that will benefit from the liquid biopsy test result in smaller and more accurate clinical studies for liquid biopsy tests.
Breakthrough designation	Requested before pre‐submission meetings. Enhance regulatory review communications for the liquid biopsy product.
Third‐party review	Novel approach, which in the case of the MSK‐IMPACT panel led to essentially simultaneous New York State Department of Health and FDA approvals.
CDx vs. other NGS genes and variants	PMA classifications and clinical utility demonstrations are expected for both novel as well as follow‐up CDx sequences. Other sequences of potential value in therapeutic decision making require only analytical validation to be included in the final reportable result.

CDx, companion diagnostics; CLIA, Clinical Laboratory Improvement Amendment; FDA, US Food and Drug Administration; NGS, next‐generation sequencing; PMA, premarket approval.