Test Categories: IVD, LDT, ASR, RUO

Why the category matters

What a lab must do before reporting patient results depends on where the test came from. Under CLIA, an unmodified FDA-cleared or approved test needs verification; a modified test or a laboratory-developed test needs full validation ¹. The next lesson covers both. First, the categories.

FDA-cleared and approved tests

An in vitro diagnostic (IVD) kit that FDA has cleared (510(k) or De Novo) or approved (premarket approval, for higher-risk tests such as many companion diagnostics) comes with a package insert defining its intended use, specimen types, procedure, and performance.

Used exactly as labeled, it’s an unmodified IVD. The lab verifies it can reproduce the manufacturer’s accuracy, precision, reportable range, and reference intervals ¹.

Changing anything material makes it a modified FDA test:

• A different specimen type (rectal swabs on an assay cleared for urine).
• A different extraction method or instrument.
• Changed volumes, cycling, or cutoffs.
• A different patient population or intended use.

Modified tests are treated like LDTs: the lab must establish performance ¹.

Laboratory-developed tests

A laboratory-developed test (LDT) is designed, validated, and used within a single CLIA-certified high-complexity lab. Much molecular testing is LDTs: rare-disease sequencing, many oncology panels, MRD assays.

For decades FDA claimed authority over LDTs but used enforcement discretion. In May 2024 it issued a rule to phase in device requirements for LDTs. On March 31, 2025, the U.S. District Court for the Eastern District of Texas vacated that rule in ACLA v. FDA and AMP v. FDA, holding that LDTs aren’t “devices” under the Food, Drug, and Cosmetic Act ². FDA formally rescinded the rule effective September 19, 2025 ³. LDTs remain regulated through CLIA (and states such as New York).

Analyte-specific reagents

An analyte-specific reagent (ASR) is a building block - an antibody, a specific primer or probe set - sold for labs to build their own tests. Rules ⁴:

• ASRs may be sold only to IVD manufacturers, CLIA high-complexity laboratories, and organizations using them for non-diagnostic purposes.
• Labels read: “Analyte Specific Reagent. Analytical and performance characteristics are not established.”
• A test built in-house with ASRs carries a report statement that the test “was developed and its performance characteristics determined by (Laboratory Name). It has not been cleared or approved by the U.S. Food and Drug Administration.”

General purpose reagents (buffers, polymerases, nucleotides) aren’t specific to an analyte and carry no such restrictions.

RUO and IUO

• Research Use Only (RUO): labeled “For Research Use Only. Not for use in diagnostic procedures.” ⁵. Instruments and reagents sold for research aren’t meant for clinical testing. A lab that does use an RUO component in a clinical LDT takes on full responsibility for validating it, and regulators and accreditors look hard at the practice.
• Investigational Use Only (IUO): products in clinical investigation, labeled “For Investigational Use Only. The performance characteristics of this product have not been established.” ⁵.

CLIA complexity

Separately, FDA categorizes tests by complexity for CLIA: waived, moderate, or high. Most molecular tests are high complexity, and all LDTs are high complexity by default. A growing number of simple sample-to-answer molecular tests are CLIA-waived (the first molecular waiver came in 2015), which is moving molecular testing into clinics and pharmacies.

What to take from this

An unmodified FDA-cleared or approved test is verified; a modified test or LDT must be fully validated. ASRs are sold only to manufacturers, high-complexity labs, and non-diagnostic users, with a fixed label and a report disclaimer for in-house tests. RUO and IUO products carry their own label statements and aren’t intended for routine diagnosis. FDA’s 2024 LDT rule was vacated in March 2025 and rescinded that September, so LDTs remain under CLIA.