What Is a Biomarker in Drug Testing?

In federal workplace drug testing, a biomarker is "an endogenous substance used to validate a biological specimen," as defined in Section 1.5 of the HHS Mandatory Guidelines for both urine and oral fluid. A biomarker is a substance the body produces naturally. Its absence, or an unusual concentration, can show that a specimen is not genuine human urine or oral fluid.

How biomarkers are used. Under both sets of HHS guidelines, a laboratory reports a specimen as substituted when a biomarker is not detected, or is present at a concentration inconsistent with human urine or oral fluid, on both the initial and confirmatory tests using the analytes and cutoffs in the biomarker testing panel (urine and oral fluid Section 3.7). Part 40 gives albumin and immunoglobulin G (IgG) as examples of biomarkers a laboratory may test in oral fluid (49 CFR 40.93).

Current status. In its most recent testing panel notice, published March 13, 2026 (91 FR 12308), HHS states that SAMHSA has not yet authorized routine testing for any biomarker in urine or oral fluid. HHS-certified laboratories (and, for urine, IITFs upon Medical Review Officer request) may request authorization to test federal agency specimens for a biomarker by submitting supporting documentation and assay validation records to the National Laboratory Certification Program for SAMHSA review and approval. In its January 16, 2025 panel notice (90 FR 4662), HHS noted that creatinine in urine meets the definition of a biomarker but is not sufficient as a sole analyte, and that the urine guidelines require testing both creatinine and specific gravity.

Pending proposals. HHS has proposed revisions to the urine and oral fluid guidelines (FR 2026-22122 and FR 2026-22121). Both proposals would require a laboratory to obtain HHS authorization before testing federal agency specimens for a biomarker, and both would allow a split testing laboratory to test for any HHS-authorized biomarker to reconfirm substitution. The urine proposal would also allow a Medical Review Officer (MRO) to authorize a biomarker test for a specimen with an invalid result based on creatinine and specific gravity. The proposals are not final.

The FAQ on oral fluid versus urine testing covers related validity testing.