The emergence of next-generation sequencing (NGS) technologies has marked a critical advancement for clinicians in the transformation of diagnosis and disease management—from cancer to rare genetic disorders. This technological impact is accelerating alongside a rapid market expansion: the global market is projected to grow from $11.8 billion this year to $38.34 billion by 2034.
This rapid growth brings significant challenges for labs, particularly when it comes to navigating the evolving regulatory guidelines for NGS testing. To stay in compliance with the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), and other agencies overseeing diagnostic devices, labs must develop robust validation infrastructures, with standardized procedures to guarantee quality and traceability.
Validate the scalability of bioinformatics platforms
One of the biggest challenges facing NGS developers is the requirement that they validate their bioinformatics platforms to demonstrate that their analytical methods can be scaled up without hampering results. After all, a bioinformatics platform that has been used to successfully process 1,000 samples may look very different when put to the test with 100,000 samples if it has not been properly validated. Any lab that creates its own bioinformatics platform must take the time to collect a sufficiently robust sample set to adequately validate it.
An alternative strategy that can ease the regulatory pathway is to use off-the-shelf bioinformatics platforms. These platforms have already been put through rigorous validation processes with data that has been collected over time, helping to ensure the consistency of the output.
Optimize reagent selection
Another hurdle NGS assay developers face is the need to establish standardized practices for the specification, validation, and quality control of reagents. When labs depend on research-use-only (RUO) reagents in their NGS workflows, due to their regulatory status, the use of such reagents often requires labs to validate each new lot they used within their assay workflow.
A solution to this challenge is to use reagents that are classified as in vitro diagnostic (IVD) when possible. Reagents classified as IVD not only offer a clear pathway to reducing lot-to-lot validation burden but also come with higher quality assurance requirements. Oftentimes, labs shy away from IVD-grade reagents for cost reasons—they can be twice as expensive as RUO-grade reagents, but ultimately, IVD-grade reagents could potentially reduce a lab’s overall costs. A thorough cost and risk analysis to understand laboratory throughput, potential quality events, and deviation activities associated with the historical use of RUO reagents may be a helpful tool in assessing the right pathway for your laboratory.
In Europe, labs developing and marketing NGS diagnostics now have an added incentive to use IVD-grade reagents. Under the recently updated In Vitro Diagnostic Medical Device Regulation (IVDR), labs must use IVD reagents, if available, regardless of cost. While enforcement of such provisions remains unclear as the regulatory environment evolves, addressing this requirement early during new assay implementation is likely to be beneficial in the future and alleviate the need for costly remediation.
Choose vendors with regulatory chops
Partnering with vendors that have deep regulatory experience can help clinical labs establish and maintain robust workflows that meet regulatory requirements, while at the same time offering flexibility. It’s important to choose technology providers that can accommodate widely used sample types, such as DNA and RNA, even when the samples are low-input or degraded. From there, considering vendors whose IVD-grade reagents can be manually prepared or automated without requiring specific instrumentation allows a lab maximum flexibility to build their assays using readily available instruments with minimal-to-no additional investment.
Most labs will face audits from regulatory agencies and certification requirements from organizations such as the Centers for Medicare & Medicaid Services, which administers the Clinical Laboratory Improvement Amendments (CLIA) quality standards for labs that handle human samples. These organizations require stringent, precise documentation that validates the specific components of workflows. Partnering with vendors that have the know-how to anticipate and support compliance with regulatory requirements can ensure clinical labs are providing the information these agencies need.
The future of precision diagnostics cannot be shaped by harnessing the power of NGS technology alone. Strong collaboration between clinical labs and NGS providers can create partnerships that accelerate the path toward accurate and actionable insights for patient care.
