A Liquid Biopsy Assay Validation Challenge

About Fulgent Genetics

Fulgent Genetics is a technology-driven leader in flexible and affordable diagnostics and therapeutics spanning oncology, infectious and rare diseases, and reproductive health. Founded in 2011, the company has evolved into a premier, full-service genomic testing company built around a foundational technology platform — including over 18,000 single-gene tests and more than 200 multi-gene panels—transforming patient care through innovation and scale.

Enter Reference Medicine - A partner with deep oncology specimen and data access

Reference Medicine brought a fundamentally different model to the table, delivering a curated, centralized inventory with standardized collection protocols (SOPs), transparent pricing, and robust metadata. For Fulgent, this meant:

• Availability: Consistent access to rare and hard-to-find matched samples that other vendors lacked
• Speed: Specimens delivered in weeks, not months or years, reducing bottlenecks at the start of validation
• Complete data: Comprehensive clinical and genomic information, continually updated as new outcomes emerged
• Cost efficiency: No wasted spend on low-quality or unusable samples—every purchase was purposeful

Matched biospecimen sets in action: Liquid biopsy assay validation

One high-stakes validation project highlights how the partnership worked in practice. For its liquid biopsy assay, Fulgent needed matched tumor tissue, plasma, and buffy coat samples for a tissue-informed validation approach for their new liquid biopsy assay.

This is where the distinction between plasma-only validation and tissue-informed validation becomes critical. Many labs validate liquid biopsy tests using only circulating DNA from plasma. While this can demonstrate technical reproducibility, it leaves unanswered the most important clinical question: Does the variant seen in the liquid biopsy actually reflect the biology of the tumor in that same patient? Without matched tissue to serve as the ground truth, a plasma-only approach risks false negatives, spurious positives, and limited credibility with regulators, payers, and clinicians.

Other vendors promised access but failed to deliver: Some shipments were indefinitely delayed; others lacked the variant data required. Without these samples, Fulgent’s team potentially faced years of additional study—delaying product launch and reimbursement.

Reference Medicine rose to the challenge. Within weeks, the team provided verified matched sets with complete genomic data, allowing Fulgent to directly compare circulating tumor DNA results against the corresponding tumor tissue. This tissue-anchored validation dramatically increased the confidence in assay performance, satisfied stringent regulatory requirements, and positioned Fulgent’s test as not only technically sound but clinically trustworthy.

This enabled Fulgent to complete validation in months rather than years, satisfy stringent regulatory requirements without compromise, and launch their assay into clinical use faster, with high confidence.

“We were able to finish this validation in a few months and get it approved and on the market. Working with Reference Medicine circumvented other options that would’ve taken years.”

— Phil Stafford, PhD, VP Bioinformatics & Regulatory, Fulgent Genetics

Unlocking tissue-informed validation

Before Reference Medicine, matched biospecimen sets that combined tumor tissue, plasma, and germline controls were almost impossible to access. Researchers had to choose between working with only plasma samples or cobbling together partial datasets from disparate vendors — approaches that could not definitively tie liquid biopsy findings back to the patient’s actual tumor biology. The result was a scientific and regulatory ceiling: assays could be optimized for sensitivity and specificity in blood, but they could not be proven against the “ground truth” of the tissue itself.

This limitation shaped the first generation of liquid biopsy tests. Developers did the best they could within the constraints, validating assays for consistency in plasma while acknowledging that unknowns remained. Variants detected in blood might or might not be present in the tumor. Missed variants could simply reflect biological shedding patterns rather than assay performance. Regulators and payers, aware of these gaps, often treated plasma-only validations with caution — slowing approvals, limiting reimbursement, and tempering clinical adoption.

Reference Medicine’s purpose-built workflows changed this paradigm. By systematically procuring and quality-controlling matched tumor, plasma, and buffy coat sets from the same patient, the company created a new categorical resource for biospecimens. For the first time, liquid biopsy developers could rigorously validate their assays in a tissue-informed way— comparing blood-based results directly against the tumor’s genomic profile. This not only raised confidence in assay performance but also accelerated regulatory timelines, unlocked reimbursement potential, and gave clinicians confidence that liquid biopsy results reflect true tumor biology.

The ability to validate against tissue has transformed liquid biopsy from a promising technology into a clinically robust tool. What was once a best-effort validation process constrained by specimen availability is now a high-confidence pathway to faster approvals, broader adoption, and ultimately, better patient care.