Galbo et al. have published, "A Comprehensive Guide to Achieving New York State Clinical Laboratory Evaluation Program Approval for Next-Generation Sequencing Assays," in J Molec Dx, March 28, 2025. Even better, it's open-access.
Many labs have to get NYState approval, either because they're based in NY State, or have patients who originate in NYState. What's more, understanding this template for NYState approval for NGS tests will probably give you a leg-up with Medicare MolDx tech assessment as well (a review system that has no comparable publication.)
Find it here:
https://www.jmdjournal.org/article/S1525-1578(25)00067-4/fulltext
17 pages.
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Here’s a detailed summary of the new Galbo et al. 2025 Journal of Molecular Diagnostics paper for your genomic policy blog readers:
Galbo et al., 2025: A Practical Roadmap for NY State CLEP Approval of NGS Assays
Title: A Comprehensive Guide to Achieving New York State Clinical Laboratory Evaluation Program Approval for Next-Generation Sequencing Assays
Authors: Galbo, Klees, Burgher, Miles, Morrison, and Glenn
Journal: Journal of Molecular Diagnostics, April 2025
Link: https://doi.org/10.1016/j.jmoldx.2025.02.009
Why This Paper Matters
Given a prominent role in FDA's plan to regulate LDTs, New York State's CLEP program offers a longstanding and rigorous model for oversight.
However, detailed peer-reviewed documentation of what CLEP actually requires—especially for complex NGS oncology panels—has been limited. This paper addresses that gap.
What’s in the Paper
The authors walk readers through step-by-step CLEP approval using their own in-house validated assay—RPPH (Rapid Pan-Heme)—as a case study. RPPH is a DNA/RNA-based NGS assay targeting >400 genes relevant to hematologic malignancies.
Key features of the paper include:
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Structure of CLEP Approval: CLEP validation is broken down into six major phases:
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SOP documentation
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Quality control (QC) metrics
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Run-level control requirements
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Analytical validation for accuracy
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Precision/reproducibility studies
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Clinical reporting
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Detailed Protocols: The paper provides meticulous documentation of wet lab methods for DNA and RNA workflows (e.g., extraction, library prep, sequencing on Illumina NextSeq, QC thresholds).
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QC Criteria and Controls: It defines exact metrics for pass/fail thresholds (e.g., >90% coverage at 200×, SNV/indel detection ≥80% in positive controls, contamination cutoffs in NTCs).
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Performance Studies:
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Batch size impact: The RPPH panel shows high concordance (≥98%) for SNVs, indels, and fusions across batch sizes from 1 to 21 samples.
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Sensitivity studies: Variant detection was reliable down to VAF ~5%, but sensitivity dropped sharply below that—particularly for indels.
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Orthogonal validation: Over 200 SNVs and 200 indels were confirmed using Sanger sequencing, achieving ~98% concordance.
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Fusion Detection: RNA-based fusion detection showed robust performance, with 100% detection of known fusions in positive controls and low false positives in NTCs.
Who Should Download This
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Lab directors navigating CLEP submissions
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Regulatory consultants preparing for increased LDT scrutiny
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Molecular pathologists seeking a CLEP-aligned SOP template
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Assay developers designing new heme panels or preparing orthogonal validation datasets
Bottom Line
This paper isn’t just a report of a validated assay—it’s a roadmap for CLEP approval. Think of it as both a how-to manual and a regulatory benchmark. For labs seeking New York approval—or preparing for a future FDA-aligned world—this is one of the most practically useful publications in recent years.
Let me know if you’d like a one-slide version of this summary or a visual comparing CLEP to FDA expectations.