CLIA 101: Answers to your most common questions about CLIA- waived tests

These early regulations primarily covered independent and hospital labs. In 1988, a second amendment was passed providing oversight to all laboratory related facilities that also included physician’s offices.

Prior to this point, there were no standard guidelines for regulating laboratory diagnostics or point-of-care laboratory testing in the United States, according to Lisa Bakken, director of laboratory consulting services for McKesson Laboratory Solutions.

These regulations are now the gold standard for every laboratory and must be followed to the letter to avoid sanctioning or shut downs.

Here, we answer some key questions about CLIA and CLIA-waived tests.

1. What is CLIA?

The Clinical Laboratory Improvement Amendments (CLIA) is the federal program that establishes quality laboratory standards to protect patient safety and improve healthcare for laboratory testing performed on humans.¹ The Centers for Medicare & Medicaid Services (CMS) oversees its regulation.

2. What is the main purpose of CLIA?

The CLIA program regulates labs that perform laboratory testing (and diagnostics) on human specimens to maintain the accuracy, reliability and reporting of patient tests and results. It regulates specific types of tests performed, as well as the training and education of personnel, quality control and the timeliness and accuracy of test results.

CLIA inspectors in the 50 states report their findings to CMS, which is how CMS determines a laboratory’s level of quality.

3. What are some common deficiencies that inspections find?

Some common deficiencies that may prevent a laboratory from receiving CLIA certification include:

• Missing signatures of the laboratory director
• Missing policy procedures
• Lack of competency assessments
• Incomplete validations of instrumentation
• Not performing competency assessments on staff
• Incomplete quality assurance plan and quality monitoring

4. What are the main three testing categories of CLIA?²

• CLIA-waived tests are simple to perform and carry a low risk of an incorrect result. These include some of the basic tests used at patient bedside settings, and are often available over the counter to consumers
  • Examples include: urine pregnancy tests, rapid strep tests, dipsticks for urine chemistry testing, glucometers, etc.
• Moderately complex tests are typically found in clinical laboratory instrumentation. Facilities using these types of tests need to complete a proper instrument validation process to show proof of accurate testing, which includes precision, accuracy, verification of reportable range, and reference intervals or reference range for the patient population within the geographical area
  • Examples include: chemistry panels, complete blood counts (CBC), some molecular (PCR) testing, urine dipsticks, urine drug screens and automated immunoassay tests
• High complexity tests require clinical laboratory expertise beyond normal automation to perform
  • Examples include: lipid chromatography-mass spectrometry (LCMS), cytology, flow cytometry, gel electrophoresis and most molecular diagnostic tests that include gene chip array, dot blots, viral loads, expression arrays and CGH arrays

5. What are the different types of CLIA certificates? What are the CLIA certification requirements? How can a laboratory provider apply for certification?

CLIA generally requires facilities that perform a single test, including CLIA-waived tests (more on those below), to obtain a CLIA certificate.

There are five types of CLIA certificates based on the test’s complexity. Exceptions to this rule are New York state and Washington state, which have “exempt” status and operate their own laboratory regulatory programs.

The five types of CLIA certificates are as follows (laboratories are designated based on the highest level of testing performed they require):

1. Certificate of Waiver: The most basic certificate allows any lab to perform any CLIA-waived tests only
2. Certificate of Provider-Performed-Microscopy Procedures: This certificate is for laboratories performing microscopy testing (for example, KOH preps, reviewing slides under a microscope for parasites)
3. Certificate of Registration: Some states require state inspections prior to a lab performing patient testing and prior to CLIA inspection³
4. Certificate of Compliance: This is a certificate granted after an inspection if a laboratory is doing moderate to complex testing, and/or any wet mounts, indicating that the laboratory is meeting the regulatory CLIA standards. The inspection schedule is typically every two years
5. Certificate of Accreditation: Any independent group where CLIA maintains governance but has regulatory oversight (such as COLA, CAP or the Joint Commission) that must obtain CLIA’s accreditation and regulatory standards. The inspection schedule is typically every two years

6. What are the most current CLIA regulations? Do they vary by state?

CLIA regulations break down into subparts. They are:

• Subpart A: General Provisions
• Subpart B: Certificate of Waiver
• Subpart C: Registration Certificate, Certificate for Provider Performed Microscopy Procedures and Certificate of Compliance
• Subpart D: Certificate of Accreditation
• Subpart H: Participation in Proficiency Testing for Laboratories Performing Nonwaived Testing
• Subpart J: Facility Administration for Nonwaived Testing
• Subpart K: Quality System for Nonwaived Testing
• Subpart M: Personnel for Nonwaived Testing
• Subpart Q: Inspection

State, local and accreditation requirements may prove more stringent, but they must all meet the CLIA standards. CLIA is the governing body for all labs in the U.S. outside of military installations.

7. How have CLIA regulations changed/modified during COVID-19?

Throughout the COVID-19 pandemic, the FDA has issued Emergency Use Authorizations (EUAs) to hundreds of vendors and manufacturers of test kits, but this does not modify CLIA law.

Laboratories must still follow all written protocols provided by the vendor or manufacturer and only perform the highest level of testing allowed by their CLIA certificate.

Most COVID-19 tests on the market have only been granted emergency use by the FDA and have a time limit/expiration date on their usage that can change at any time.

8. What are CLIA personnel requirements?

Personnel requirements vary based on test complexity and state requirements. Each state may have their own state regulations and governance that applies (for example, personnel licensure in addition to certification).

9. Are all labs subject to CLIA? Are there any exceptions?

The exceptions to CLIA certification include forensic and research labs that test human specimens but do not report patient-specific results for the diagnosis, prevention or treatment of any disease or impairment of or assessment of the health of individual patients.

Some laboratories may also be exempt if only certified by the Substance Abuse and Mental Health Services Administration (SAMHSA) for toxicology. All other testing conducted by a SAMHSA-certified lab requires a CLIA certificate.

In a nutshell, if it’s a research lab and performing human tests but not providing test results or subsequent treatment for a patient, a CLIA certificate is not required.

10. What is a CLIA waived test? Is this the same as a CLIA Certificate of Waiver?

A waived test is a simple point-of-care (POC) test whose process uses a one- to two-step process, requiring minimal interpretation and rarely requires special training to perform (for example, a urine pregnancy test or a blood glucose test). A CLIA certificate is still required to perform a CLIA-waived test.

11. Which tests can receive a waiver?

A CLIA-waived test is categorized as a simple laboratory examination or procedures that has a low likelihood of an erroneous result according to CLIA^.4 The FDA determines whether a test qualifies as waived or not. However, the method or process of specimen collection can also change the FDA’s designation/classification for a laboratory test. A list of all waived tests can be found at the FDA website.⁵

12. Who can perform CLIA-waived testing?

There are no CLIA personnel requirements for waived testing, but this can depend on the state. A laboratory must have a laboratory director, and in a couple of states, such as Maryland, this director must be an M.D.

13. What is a laboratory-developed test (LDT)?

An LDT is a highly complex test. Typically, these tests are not distributed or sold commercially. These are tests developed in-house in a healthcare facility, independent or reference laboratory and approved by the medical/laboratory director in order to perform and provide results on their own.

An LDT is also any FDA approved commercial test that a lab has modified in any way. Any modifications (testing or other) outside of approval under section 510(k) of the Food, Drug and Cosmetic Act⁶ — intent to register a medical device — renders this test high-complexity and is subject to the regulations applied to all LDTs.

14. What does CMS CLIA require for analytical validity for LDTs?

The federal government, through the CLIA program, thoroughly regulates the evaluation and use of all lab tests including lab-developed assays.

CLIA states that a lab must demonstrate how well the noncommercial and commercial tests perform. The performance specifications are: accuracy, precision, test sensitivity and test specificity.

In addition, the FDA requires validation of a test’s clinical utility. The test should measurably improve health outcomes and show that using it leads to better health benefits. LDT validations are lengthier in nature and require more rigorous proof by the individual lab.

15. What’s the difference between the CMS’s analytical validity review versus the FDA’s analytical validity review for LDTs?

CMS is the federal agency responsible for ensuring the accuracy and quality of an LDT. The FDA provides guidance on how to categorize these tests. The FDA informed Congress of its plans to develop a new draft risk-based approach for overseeing LDTs.⁷

16. How often does a CLIA certification require renewal?

CLIA certification must be renewed every two years. In addition to the renewal fees, there may be inspections and/or regulatory audits involved with the process.

17. What are the three agencies and their roles in assuring quality laboratory testing?

• FDA: Categorizes tests based on complexity; reviews requests for waivers by application; develops rules/guidance for CLIA complexity categorization
• CMS: Issues laboratory certificates; collects user fees; conducts inspections and enforces regulatory compliance; approves private accreditation organizations for performing inspections and approves state exemptions; monitors laboratory performance on proficiency testing (PT) and approves PT programs; publishes CLIA rules and regulations
• CDC: Provides analysis, research and technical assistance; develops technical standards and laboratory practice guidelines, including standards and guidelines for cytology; conducts laboratory quality improvement studies; monitors proficiency testing practices; develops and distributes professional information and educational resources; manages the Clinical Laboratory Improvement Advisory Committee (CLIAC)

Conclusion

To successfully run a laboratory in the United States, clinicians must adhere to CLIA standards, prepare for a CLIA inspection every two years and correct any errors found in such an inspection to remain in operation.

However, laboratories should also check with state/local guidelines to determine if there are additional regulations to follow.