CLIA Waived Tests: What Labs Can Perform Under a Certificate of Waiver

What Makes a Test Waived

The CLIA statute defines waived tests as "simple laboratory examinations and procedures that have an insignificant risk of an erroneous result." This definition has two components that work together. The test must be simple enough that an untrained person can perform it correctly by following instructions, and the consequences of an incorrect result must be low enough that the error would not reasonably harm the patient or cause them to seek inappropriate treatment.

The FDA makes the determination of whether a specific test system meets these criteria. No test category is automatically waived by virtue of what it measures. A glucose test on one manufacturer's device may be waived; a glucose test on a different device that requires additional sample processing steps may be classified as moderate complexity. The waiver is granted to a specific test system, not to an analyte in the abstract. This is why the FDA waived analytes list is organized by analyte and linked to the individual test systems cleared under each one.^[2]

The Three FDA Waiver Pathways

FDA grants waiver through three distinct pathways, each with different requirements for the manufacturer.^[2]

FDA maintains the complete database of all waived analytes at accessdata.fda.gov. Selecting an analyte from the list opens the specific test systems cleared under that analyte, including the manufacturer name, device name, and the FDA database record number. The list is continuously updated as new tests are approved. A laboratory should always verify waived status for any new test through the FDA database before ordering the test under a CoW certificate.^[2]

The 155 Waived Analytes: A Clinical Overview

The FDA currently recognizes 155 unique waived analytes across five broad clinical categories. The number of analytes understates the actual number of waived test systems, because multiple manufacturers may offer different waived devices for the same analyte. The categories below reflect the clinical scope of what a CoW laboratory can test for.

Chemistry and metabolic testing (34 analytes)

This is the largest single category, covering many of the most commonly ordered point-of-care tests. Waived chemistry analytes include glucose (in multiple device categories including home-use meters, prescription meters, and fluid glucose), cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, HbA1c (glycosylated hemoglobin), creatinine, urea (BUN), uric acid, albumin, microalbumin, bilirubin (total), alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), B-type natriuretic peptide (BNP), prothrombin time (PT), lactic acid, ionized calcium, total calcium, sodium, potassium, chloride, phosphorus, carbon dioxide, lithium, and fructosamine.

The clinical breadth here is notable. A physician office holding only a CoW can test for cardiac risk factors (cholesterol, triglycerides, LDL/HDL), diabetes monitoring (glucose, HbA1c, microalbumin), kidney function (creatinine, BUN), liver function (ALT, AST, ALP, GGT, bilirubin), electrolytes, coagulation (prothrombin time for patients on warfarin), and heart failure screening (BNP) all without requiring a nonwaived certificate.^[1]

Infectious disease testing (24 analytes)

Infectious disease is the category that expanded most dramatically following the COVID-19 pandemic. Current waived infectious disease analytes include influenza A, influenza B, and combined influenza A/B; SARS-CoV-2; SARS-CoV-2 combined with other respiratory viruses; respiratory syncytial virus (RSV); Group A Streptococcus; Helicobacter pylori (antigen and antibody); HIV-1 antibody, HIV-1 and HIV-2 antibodies, and HIV-1/HIV-2 antigen/antibody combination tests; hepatitis C virus antibody and HCV RNA; herpes simplex I and/or II antibodies; chlamydia; Neisseria gonorrhoeae; Trichomonas; Candida (yeast only); Lyme disease antibodies; Treponema pallidum (syphilis) antibodies; and infectious mononucleosis antibodies.^[2]

Several of these analytes carry requirements for confirmatory testing that a CoW site cannot perform in-house. A reactive rapid HIV test, a reactive rapid syphilis test, and a reactive rapid hepatitis C test all require follow-up testing at a nonwaived laboratory before a definitive diagnosis can be communicated to the patient. The CoW site should have a referral laboratory relationship established before offering these tests.

Urinalysis (17 analytes)

Urinalysis is one of the original waived categories. Waived urinalysis analytes include urine dipstick or tablet analytes (nonautomated), urine qualitative dipstick tests for bilirubin, blood, creatinine, glucose, ketone, leukocytes, nitrite, pH, protein, specific gravity, urobilinogen, and ascorbic acid, as well as urinary leukocyte esterase, urinary nitrite, urinary albumin, and qualitative urinary protein. Urine hCG (pregnancy) by visual color comparison is also in this category.^[2]

The "nonautomated" qualifier on several dipstick analytes is operationally significant. Automated urine dipstick readers that process the strip and produce an electronic result are frequently classified as moderate complexity rather than waived. A laboratory that switches from reading dipstick results visually to using an automated reader must verify the specific reader's complexity classification before continuing to operate under a CoW.

Hematology (11 analytes)

Waived hematology analytes include hemoglobin, hematocrit, spun microhematocrit, hemoglobin by copper sulfate (nonautomated), glycated hemoglobin (HbA1c), glycosylated hemoglobin, erythrocyte sedimentation rate (nonautomated), red blood cell count, white blood cell count, white blood cell differential, and platelet count and platelet aggregation.

The same nonautomated qualifier applies here. Many common automated hematology analyzers are classified as moderate complexity. A physician office using an automated complete blood count (CBC) analyzer is almost certainly operating under a nonwaived requirement, regardless of how simple the device seems. The complexity classification is determined by the specific instrument, not by the analyte being measured.

Drug testing (20 analytes)

The drug testing category covers a range of substances relevant to pain management clinics, urgent care, occupational health, and addiction medicine. Waived drug testing analytes include amphetamines, methamphetamine/amphetamine, cannabinoids (THC), cocaine metabolites, opiates, oxycodone, morphine, 6-acetylmorphine, phencyclidine (PCP), benzodiazepines, barbiturates, buprenorphine, methadone, methadone metabolite (EDDP), fentanyl, norfentanyl, tramadol, propoxyphene, cotinine (nicotine metabolite), oxazepam, and ethanol/alcohol (saliva).

An important distinction applies here. Drug testing for employment purposes under SAMHSA-certified programs is exempt from CLIA entirely, as described in the What Is CLIA article. However, drug testing performed for clinical purposes, including medication compliance monitoring in chronic pain patients, is subject to CLIA and requires a CoW for waived tests or a nonwaived certificate for confirmatory or quantitative testing.

Other clinical categories (49 analytes)

A substantial group of waived analytes falls outside the major categories above. These include thyroid stimulating hormone (TSH), follicle stimulating hormone (FSH), luteinizing hormone (LH) and ovulation tests, lead in blood, amylase, creatine kinase (CK), immunoglobulins IgE, vaginal pH, fern test (saliva), bacterial vaginosis organisms, respiratory bacterial pathogens, Bordetella species, Mycoplasma genitalium, adenovirus, osmolality of tears, host biomarker proteins, matrix metalloproteinase-9 (MMP-9), various urine and blood ketone tests, total protein, collagen crosslinks, pregnanediol glucuronide, several tricyclic antidepressants, nortriptyline, semen analysis, and gastric and bladder tumor markers.^[2]

What a Certificate of Waiver Requires

The Certificate of Waiver is the least burdensome CLIA certificate category, but it is not obligation-free. The regulatory requirements for a CoW laboratory are fewer than those for nonwaived labs, but they are specific and non-negotiable.^[4]

• The site may only perform tests that are classified as waived. Performing any nonwaived test under a CoW is a regulatory violation.
• All testing personnel must follow the current manufacturer's instructions for every waived test being performed.
• The CoW certificate must be renewed every two years, including payment of the biennial certificate fee.
• The State Agency must be notified within 30 days of any change in ownership, name, location, or laboratory director.
• The State Agency must be notified immediately, before testing begins, if the site wishes to add any test that is not waived to its menu.
• The site must allow CMS representatives on-site for announced or unannounced inspections when CMS determines one is warranted.
• All applicable state and local requirements must be followed, including any state personnel licensure or phlebotomy regulations, which vary significantly by state.

There are no CLIA requirements under a CoW for personnel qualifications, quality control frequency beyond what the manufacturer specifies, quality system documentation, or proficiency testing enrollment. However, the complete absence of these requirements means the laboratory director or person overseeing testing must make deliberate decisions about each of them rather than simply following a regulatory checklist.

The Manufacturer's Instructions Rule

The single most important operational requirement for a CoW laboratory is following the current manufacturer's instructions for each test. Studies of problems found at waived testing sites consistently identify failure to follow manufacturer instructions as the most common cause of incorrect results. This rule has several practical dimensions that are easy to overlook.^[3]

The instructions must be current. Manufacturers periodically update their instructions as new data accumulates, and the instructions that came with a test kit purchased a year ago may no longer reflect the current approved procedure. When a new lot or shipment of reagents or test kits arrives, the instructions should be checked for changes and compared against previous versions. If instructions have changed, the new version replaces the old and must be communicated to all testing personnel.

Quick reference cards are not a substitute. Many manufacturers provide a quick reference instruction card or poster to post in the testing area. These cards are a supplement to the full package insert, not a replacement. The full manufacturer's instructions must remain on hand at the testing site. If the manufacturer updates the full instructions, the quick reference card may also need to be updated. Testing performed using only a quick reference card, without access to the full instructions, is not in compliance with the CoW requirement.

Instructions are test-system-specific. The instructions for one manufacturer's glucose meter do not apply to another manufacturer's glucose meter, even if they measure the same analyte. Reagents and supplies from different manufacturers or different lot numbers should never be mixed or substituted between test kits, because the waiver applies to the entire test system as a unit, and substituting components is a modification that takes the testing outside the approved procedure.

Expiration dates and storage conditions are part of the instructions. Using expired reagents or test kits, or storing them outside the temperature and humidity ranges specified in the instructions, constitutes a departure from the manufacturer's instructions. Temperature logs for reagent and test kit storage areas are a recommended practice for CoW sites precisely because storage condition failures are a common source of incorrect results.

Off-Label Use: The Hidden Compliance Risk

The most consequential misunderstanding in waived testing compliance is the assumption that using an FDA-cleared waived test system always produces waived testing. That assumption is wrong as soon as the test is used in any way not described in the manufacturer's approved instructions. Under CLIA, any modification to a waived test system, however minor it may appear, is called off-label use and is automatically reclassified as high-complexity testing.^[3]

This reclassification is not gradual. There is no intermediate step where a slightly modified waived test becomes moderate complexity. The modification jumps the testing directly to the highest complexity tier, with all the attendant requirements for proficiency testing, quality control, quality assessment, and personnel qualifications. A CoW laboratory performing off-label testing must upgrade to a Certificate of Compliance or Certificate of Accreditation to be in compliance.

Common examples of off-label use

Good Testing Practices for CoW Sites

CDC and CMS have developed extensive guidance for waived testing sites under the "Ready? Set? Test!" framework, which organizes good testing practices into three phases: before testing, during sample collection, and during and after the test itself. These recommendations exceed the minimum CLIA requirements for CoW labs but reflect the practices that reliably produce accurate results.^[3][5]

Before testing (Ready?)

• Select a testing area that is well-lit, clean, level, and stable, with adequate space to collect samples and maintain patient privacy.
• Check and record temperatures of testing, reagent, and test kit storage areas daily. Reagents stored outside the manufacturer's specified temperature range may be compromised even if they are not yet expired.
• Inspect reagents and test kits for damage, discoloration, or contamination before use. Discard any compromised materials.
• Verify that all test kit component reagents are from the same kit lot. Do not mix components between different lot numbers.
• Check expiration dates and discard expired materials. Recording lot numbers and expiration dates at the time of use is a critical element of the record-keeping system.
• Allow refrigerated reagents, test kits, and patient samples to come to room temperature before testing, as specified in the manufacturer's instructions.
• Perform quality control testing at least as often as the manufacturer's instructions specify. QC should also be run with each new shipment of reagents or test kits, with each new lot number change, and when a new staff member begins performing the test.

Sample collection (Set?)

• Verify the test order and confirm patient identity using at least two unique patient identifiers (name and date of birth) before collecting the sample.
• Follow the manufacturer's instructions for the specimen type, collection device, handling, and storage. Waived tests may only be performed on unprocessed samples. Examples of unprocessed samples include whole blood from fingerstick or anticoagulated venipuncture, urine, throat or nasal swab, saliva or oral fluid, stool, and gastric biopsy.
• Use only the collection device specified in the manufacturer's instructions or the test kit. Do not substitute swabs, lancets, or collection containers from other sources.
• Label the sample immediately after collection with at least two unique patient identifiers. If the test requires the patient's sample to be applied directly to the test device, label the device before collecting the sample.
• Wear appropriate personal protective equipment including gloves, and clean hands and change gloves between patients.

During and after the test (Test!)

• Follow the manufacturer's instructions in the exact sequence. Use a timer for all steps with specified timing intervals. Do not read results before the specified time or after the read window has closed.
• Read and record results before discarding the test device, in case questions arise later about the result.
• Invalid results require troubleshooting, not ignoring. Check for expired materials, improper storage, inadequate sample volume, and technique errors. Retest after correcting the identified issue.
• Identify and follow up on critical results. Know which results for each test require immediate clinical action and who to notify.
• When a waived test result indicates the need for confirmatory testing, refer the specimen to a nonwaived laboratory. Do not perform confirmatory testing in a CoW lab using a nonwaived method.
• Maintain records of test orders, results, QC results, reagent lot numbers and expiration dates, personnel training and competency assessments, and temperature logs. These records allow problems to be identified and resolved and support any inspections that may occur.

Quality control for waived tests

Waived test kits typically include two types of controls. Internal controls (also called procedural or built-in controls) verify that the test is working correctly, that the sample volume was adequate, and that the sample is moving through the device as expected. External controls are separate liquid or solid materials that simulate a patient sample and test the entire process from sample application through result interpretation. External controls may be included with the kit or purchased separately.

The manufacturer's instructions specify when and how to run external controls. At a minimum, QC should be performed when a new shipment of reagents or test kits arrives, whenever there is a change in lot number, and whenever a new testing staff member begins performing the test. Failing QC results require troubleshooting before patient testing continues. Patient results obtained while QC is failing may not be reportable.^[3]

When a CoW Lab Must Upgrade Its Certificate

Several situations require a CoW laboratory to obtain a higher-level certificate. Understanding these triggers prevents unintentional compliance violations.^[4]

Frequently Asked Questions