Implementing next-generation sequencing (NGS) in routine oncology practice remains a significant undertaking for many pathology laboratories. Beyond selecting the right assay, laboratories must navigate verification requirements, quality management, workflow optimization, reporting, and reimbursement – all while meeting the growing demand for rapid genomic profiling.
In a recent webinar supported by Thermo Fisher Scientific, four speakers explored how an FDA-approved in vitro diagnostic (IVD) workflow can reduce many of these barriers. Together, they presented a roadmap spanning regulatory verification, real-world laboratory implementation, integrated software, and reimbursement, illustrating how standardized workflows can help bring precision oncology testing into routine clinical practice.
Verification, Not Validation
Opening the program, Xia Li addressed a common misconception surrounding implementation of IVD NGS assays: although laboratories are accustomed to validating laboratory-developed tests (LDTs), FDA-approved assays have a much simpler verification process.
Using the Oncomine DX Express Test as an example, Li described how the assay was designed to streamline comprehensive genomic profiling for solid tumors while supporting rapid clinical decision-making.
The test generates results in as little as 24 hours from formalin-fixed, paraffin-embedded tissue, requires only 10 ng each of DNA and RNA, and features an automated workflow requiring approximately 20 minutes of hands-on time. The panel interrogates multiple classes of genomic alterations – including substitutions, insertions/deletions, copy number variants, and gene fusions or splice variants – across multiple cancer types.
The presentation's central message, however, focused on the US regulatory framework governing the assay’s implementation. "Verification is required prior to reporting results for unmodified FDA-cleared or approved non-waived test systems introduced into a laboratory," Li explained, citing Clinical Laboratory Improvement Amendments (CLIA) requirements. Unlike LDTs, which require comprehensive validation, unmodified IVD assays undergo a limited study just to confirm that manufacturer-established performance specifications can be reproduced under local laboratory conditions.
Li outlined a practical approach to verification, recommending the use of representative clinical specimens spanning multiple tumor types and variant classes (Table 1). She recommended that studies should assess analytical accuracy, precision, reportable range, and specificity.
She concluded by contrasting implementation of an FDA-approved assay with development of an LDT. "Verification has a smaller scope requiring fewer samples and less testing than for validation," she said. "It is faster and less expensive, helping the lab implement the test more efficiently."
Laboratories implementing an FDA-approved assay can maintain verification data within their own quality management systems, without the need to submit it for review, while benefiting from more predictable reimbursement pathways. With an appropriately designed verification strategy, Li explained, laboratories can introduce genomic profiling into routine practice in a matter of weeks rather than many months.
From Verification to Clinical Implementation
Where Li outlined the principles of analytical performance verification, Gary Pestano demonstrated how they translate into routine clinical practice, drawing on his laboratory's experience implementing the Oncomine DX Express Test.
"Our study objective was to compare our lab's experiences and extensive technical evaluation to the manufacturer’s approved data," he explained. His team's verification included 48 formalin-fixed, paraffin-embedded tumor specimens representing 13 different tumor types and encompassing 84 genomic variants. While the emphasis was on lung cancer, the study was broadened to include a range of specimen types and genomic alterations.
“I recommend that laboratories expand their verification cohorts to reflect the cancers most commonly encountered in their own institutions,” said Pestano
Performance was benchmarked against independently generated reference results, with any initial discrepancies investigated using orthogonal molecular methods. The outcome was a high level of analytical agreement, with final concordance reaching 98 percent at the variant level and 96 percent at the sample level.
The assay also demonstrated reliable performance across a broad spectrum of variant allele frequencies, supporting confidence in reporting both high- and low-frequency alterations encountered in patient samples. The study results are published in Mol Cell Probes.
Pestano's team complemented these studies with additional analytical verification using reference materials representing every major variant class. All expected copy number alterations and fusion events were detected, while only a single expected single nucleotide variant was initially missed. The discrepancy most likely arose from an artifact in the synthetic reference material, Pestano explained.
For Pestano, the practical advantages extended beyond concordance metrics. His laboratory found that the automated end-to-end workflow, rapid turnaround time of less than two days, and low nucleic acid input requirements supported routine adoption in time-sensitive oncology settings. "Time to treatment is a big focus for us here at Biodesix," he affirmed.
He also acknowledged the assay's intended scope. While well suited to targeted genomic profiling and companion diagnostics, its predefined gene panel is not designed for broader exploratory sequencing or applications requiring ultra-low-frequency variant detection. Even so, when interpreted alongside pathology findings and the clinical picture, Pestano concluded that the assay provides "a reliable and practical solution for delivering timely genomic insights in routine precision oncology."
Streamlining the Path from Sample to Report
Shifting the focus from assay implementation to day-to-day laboratory operations, Teresa Wheeler explored how integrated software can lower the barriers to routine clinical NGS. Her presentation centered on the Genexus DX software, which is designed to simplify the testing process by guiding users through the entire NGS workflow using just two main software interactions.
"The Genexus DX software is designed to make in-house clinical NGS testing fast and easy," Wheeler said. Rather than requiring users to navigate multiple applications or manually coordinate individual workflow steps, the platform consolidates sample management, run planning, quality control, data analysis, and reporting within a single interface.
The first software interaction occurs before sequencing begins, when laboratory staff enter sample information and create a single run plan that carries the specimen through the complete analytical workflow.
Once initiated, the system automates nucleic acid extraction, quantification, library preparation, sequencing, data analysis, and predefined quality control checks with minimal user intervention.
After transferring the prepared samples from the purification system to the integrated sequencer, the workflow resumes automatically without requiring the run to be reconfigured.
Wheeler emphasized that automation extends well beyond the sequencing run itself. Once a run has been initiated, the software continuously monitors progress while automatically performing primary analysis – including base calling and quality assessment – followed by secondary analysis, in which reads are aligned, variants are identified, and clinical reports are generated. Laboratory staff can monitor run status remotely before returning for the final review and sign-off.
"The second and last interaction with the software occurs only after analysis is complete,” Wheeler explained, “when users review quality metrics, inspect variant calls, and authorize the clinical report.” Built-in quality control thresholds are applied automatically at both the run and sample level, allowing laboratories to assess assay performance without developing custom quality control frameworks.
She also highlighted the software's ability to integrate with laboratory information management systems through application programming interfaces, allowing laboratories to automate sample registration and report transfer within existing digital infrastructures.
Wheeler concluded that simplifying software is ultimately about expanding access to precision oncology. By guiding users through standardized workflows, reducing manual intervention, and presenting clinically actionable results in an intuitive format, integrated software can help more laboratories – and more clinicians – adopt comprehensive NGS testing without requiring extensive bioinformatics expertise.
Clearing the Path to Reimbursement
The webinar concluded with a practical overview of the reimbursement landscape from Rob Dumanois, who argued that successful adoption of a new molecular assay depends not only on analytical performance, but also on a clear route to coding, coverage, and payment.
Dumanois outlined the market access strategy developed for the Oncomine Dx Express Test, highlighting the establishment of dedicated coding pathways intended to simplify billing for clinical laboratories (Table 2). "This allows CLIA labs a clear path to coverage and payment," he said, noting that laboratories billing through the MolDX program can also register the assay using an assigned Z-code with minimal administrative effort.
Regarding coverage, Dumanois explained that the assay is covered nationally by Medicare following its FDA approval, with additional commercial insurers beginning to announce reimbursement policies. Looking ahead, he described the ongoing process of establishing a national Medicare payment rate while noting that interim reimbursement has already provided encouraging signals for laboratories considering implementation.
For Dumanois, these developments complement the assay's streamlined verification pathway discussed throughout the webinar. By combining an FDA-approved workflow with defined coding, established coverage pathways, and manufacturer support for billing and payer engagement, laboratories can focus less on reimbursement uncertainty and more on delivering precision oncology testing to patients.
"The PLA code, coverage, and pricing data bring clarity," he concluded, adding that Thermo Fisher aims to work with laboratories to provide "clarity and confidence" as they introduce the test into routine clinical practice.
Toward Routine Precision Oncology
While each speaker approached implementation from a different perspective, a consistent message emerged throughout the webinar: standardization has the potential to accelerate adoption. From streamlined analytical verification and independently demonstrated laboratory performance to integrated software workflows and defined reimbursement pathways, the speakers argued that FDA-approved IVD assays can substantially reduce many of the barriers that have traditionally slowed the introduction of NGS-based genomic profiling into routine pathology practice.
As demand for precision oncology continues to grow, the challenge for laboratories is no longer simply generating high-quality sequencing data, but implementing workflows that deliver clinically actionable results rapidly, reproducibly, and sustainably. The webinar suggested that simplifying the entire testing pathway – from specimen to reimbursement – may be just as important as advances in sequencing technology itself.
For In vitro diagnostics. "The Oncomine DX Express Test is indicated in US as a companion diagnostic (CDx) to identify non-small cell lung cancer (NSCLC) patients with EGFR exon 20 insertion mutations for treatment with ZEGFROVY™ (sunvozertinib) in accordance with the approved therapeutic product labeling. The Oncomine Dx Express Test detects biomarkers recommended by professional guidelines for multiple solid tumors, including substitutions, insertions, and deletions in 42 genes, copy number variants in 10 genes, and fusions or splice variants in 18 genes.
PMR-008501
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