Analytical Validation: The Bedrock of Reliable Diagnostics

In the evolving world of diagnostics, analytical validation often sits quietly behind the scenes. Often overshadowed by its flashier cousin, clinical validation. But make no mistake: analytical validation is the bedrock of every credible diagnostic test. Without it, no claim of accuracy, reliability, or utility can stand.

As the regulatory spotlight shifts, particularly with the recent court decision stating that FDA does not have authority over laboratory developed tests (LDTs)—the burden to ensure strong analytical validation falls even more heavily on both CLIA-certified labs and FDA-regulated manufacturers. Whether you’re launching an LDT or submitting a device for clearance or approval, the same truth holds: your test must be precise, reproducible, and within defined parameters.

What Is Analytical Validation?

Analytical validation answers the fundamental question: Can the test reliably measure what it claims to measure?

This process includes:

• Accuracy: How close is the result to the true value?

• Precision: How consistent are results across runs, operators, or instruments?

• Analytical sensitivity: What is the test’s lower limit of detection?

• Analytical specificity: Can it distinguish the target analyte from others?

• Reportable range: Over what range does the test yield reliable results?

• Reference intervals: What values are expected in a healthy (“normal”) population?

• Interfering substances: What factors can skew the results?

Every one of these components matters—and cutting corners here means risking test performance downstream.

For CLIA-Certified Labs Running LDTs

Under CLIA, high-complexity labs developing and offering LDTs are required to perform rigorous analytical validation before patient results are reported. But unlike FDA requirements, the CLIA framework offers labs broad discretion in designing and documenting their processes. This flexibility is beneficial - but it also introduces risk.

In the absence of FDA oversight, labs must hold themselves accountable. Robust analytical validation isn’t just a regulatory requirement—it’s a matter of professional ethics and patient safety. Laboratories should adopt best practices from FDA guidance, CLSI standards, and peer-reviewed methods to assure the quality of their LDTs.

If you’re running an LDT today, ask yourself:

• Have we fully characterized our assay’s performance?

• Is our documentation sufficient to stand up to payer audits, malpractice claims, or scientific scrutiny?

• Are we validating for real-world use—not just under ideal lab conditions?

  
  

For Manufacturers Submitting to FDA

Manufacturers pursuing FDA clearance or approval face a different level of scrutiny. Analytical validation is a non-negotiable pillar of the submission process. The FDA requires detailed, statistically justified studies that meet specific performance thresholds and follow Good Laboratory Practices (GLP) when applicable.

Unlike CLIA, where flexibility is built in, FDA expects manufacturers to submit a full validation package—complete with protocols, raw data, summary reports, and analyses that demonstrate reproducibility, robustness, and accuracy across intended use populations and environments.

Manufacturers must also consider the test system holistically—reagents, software, instruments, and workflows—ensuring the entire system delivers valid results. This includes rigorous validation of instruments and software.  These requirements aren’t burdensome red tape. They are essential protections for the patients, clinicians, and systems that rely on diagnostic tools every day.

One Standard, Shared Responsibility

Whether you’re a CLIA lab serving your community or a manufacturer launching a national diagnostic, the responsibility is the same: Deliver reliable, reproducible, analytically sound results. Our industry thrives on trust—and trust begins with precision and reproducibility.

As regulatory frameworks shift, analytical validation remains the non-negotiable starting point for any test meant to impact patient care. It’s time we treat it that way—openly, consistently, and with the rigor it deserves.

Let’s commit to a future where every result is not just available, but reliable.