What CLIA requires of a laboratory before it reports a result

Before reporting a patient result from a test it developed itself, a laboratory must hold a CLIA certificate that covers the complexity of that test. It must also establish the performance specifications for the test system and staff the testing with personnel who meet the qualification standards in subpart M of 42 CFR part 493. A test system developed in-house falls within the establishment requirement of § 493.1253(b)(2), which is broader than the verification requirement that applies to unmodified FDA-cleared systems.¹

Certificates and the complexity category

Every laboratory must either be CLIA-exempt or hold one of five certificates: a registration certificate, a certificate of waiver, a certificate for PPM procedures, a certificate of compliance or a certificate of accreditation.² Tests are categorized as waived, moderate complexity including the PPM subcategory, or high complexity.² A laboratory may perform any combination of these categories, subject to holding the certificate that covers them.²

Categorization follows the seven criteria in § 493.17(a), each scored 1, 2 or 3. A total score of 12 or less places the test at moderate complexity and a score above 12 places it at high complexity.² For commercial test systems the manufacturer submits supporting data with its 510(k) or PMA application and FDA determines the category.² For test systems that are not commercially available, a laboratory or professional group may submit a written request for categorization to PHS, which forwards it to CDC.²

The default position matters for a laboratory-developed test. A laboratory test system, assay or examination that does not appear on the Federal Register lists is considered high complexity until PHS reviews the matter upon request and notifies the applicant.² Categorization takes effect as of the notification to the applicant.² A request for recategorization is accepted only if it rests on new information, and it is considered no more than once a year from the same applicant.²

Applying for the certificate

An application is filed separately for each laboratory location, with exceptions for mobile testing units, certain limited public health testing and contiguous hospital buildings under common direction.² The application is made on a form prescribed by HHS and signed by an owner or an authorized representative who attests that the laboratory will be operated in accordance with the Secretary’s requirements.² It must describe the name and annual number of test procedures performed, the methodologies used for each test, and the educational background, training and experience of the personnel directing, supervising and performing the testing.²

A certificate of compliance is issued only where the laboratory meets §§ 493.43 and 493.45, remits the fee in subpart F, and meets the applicable requirements of subparts H, J, K, M and Q.² The certificate is valid for no more than two years.² A laboratory seeking renewal returns the renewal application to HHS 9 to 12 months before the certificate expires.² Holders must permit announced or unannounced inspections by HHS.²

Performance specifications before the first patient result

The validation obligation sits in § 493.1253 and attaches before patient test results are reported. A laboratory that introduces an unmodified FDA-cleared or approved test system must demonstrate that it can obtain performance comparable to the manufacturer’s specifications for accuracy, precision and reportable range of test results.¹ It must also verify that the manufacturer’s reference intervals are appropriate for its own patient population.¹

A laboratory that modifies an FDA-cleared or approved test system takes on the establishment duty, as does a laboratory introducing a test system not subject to FDA clearance or approval. Methods developed in-house and standardized methods such as text book procedures fall in this group, as does any test system for which the manufacturer provides no performance specifications.¹ For each such test system the laboratory must establish the following performance specifications, as applicable.¹

• accuracy
• precision
• analytical sensitivity
• analytical specificity including interfering substances
• reportable range
• reference intervals
• any other performance characteristic required for test performance

The laboratory must then determine the calibration and control procedures for the test system on the basis of the specifications it verified or established.¹ All activities under the section must be documented.¹ The requirement reaches test systems put into use from 24 April 2003 onward.¹

Calibration, controls and result comparison

Calibration and calibration verification substantiate the continued accuracy of the test system across the reportable range.² Calibration follows the manufacturer’s instructions and the criteria verified or established under § 493.1253(b)(3), and is repeated whenever calibration verification fails the laboratory’s acceptable limits.² Calibration verification is performed at least once every six months and on the events listed in § 493.1255(b)(3), including a complete change of reagents and major preventive maintenance.²

Control procedures must monitor the accuracy and precision of the complete analytic process for each test system.² At minimum, on each day patient specimens are assayed, a quantitative procedure runs two control materials of different concentrations and a qualitative procedure runs a negative and a positive control.² A test system with an extraction phase runs two controls, one capable of detecting errors in extraction.² A molecular amplification procedure runs two controls, plus a control capable of detecting inhibition where reaction inhibition is a significant source of false negatives.² Control results must meet the laboratory’s criteria and, where applicable, the manufacturer’s criteria before patient results are reported.² Where control materials are unavailable, the laboratory must have a documented alternative mechanism to detect immediate errors and monitor performance over time.²

A laboratory performing the same test by different methods or instruments, or at multiple sites, must evaluate and define the relationship between those results twice a year.² It must also have a system to identify patient results that appear inconsistent with criteria such as patient age, sex and distribution of results.²

Proficiency testing

Enrollment in an HHS-approved proficiency testing program is a condition of participation for each specialty and subspecialty for which the laboratory seeks certification.² Samples are tested with the regular patient workload by the personnel who routinely perform the testing, using routine methods.² The testing individual and the laboratory director attest to that integration.²

For tests the laboratory performs that are not included in subpart I, the laboratory must establish and maintain the accuracy of its testing procedures in accordance with § 493.1236(c)(1).² Most laboratory-developed tests occupy this position. Proficiency testing samples must not be sent to another laboratory for any analysis the laboratory is certified to perform, and a determination of intentional referral can lead to revocation of certification for at least one year.² Records of proficiency testing, including the signed attestation, are kept for at least two years from the date of the event.²

Personnel for high complexity testing

The laboratory director must hold a current State director licence where the State requires one, and must meet one of the qualification routes in § 493.1443(b).² These include board certification in anatomic or clinical pathology, or a medical, osteopathic or podiatric degree with at least two years directing or supervising high complexity testing and 20 CE credit hours in laboratory practice.² A doctoral route requires an approved board certification and two years of laboratory training or experience. It also requires two years directing or supervising high complexity testing and 20 CE credit hours.² An individual qualified and serving as a high complexity laboratory director in a CLIA-certified laboratory as of 28 December 2024, continuously since that date, is considered qualified.²

The director must be on site at least once every six months, with at least four months between the two minimum visits, and must document those visits.² An individual may direct no more than five laboratories.² Among the director’s duties are ensuring that verification procedures are adequate to determine accuracy, precision and other performance characteristics, and specifying in writing what each individual is authorized to perform.²

The laboratory must employ technical supervision for each specialty and subspecialty in which it performs high complexity tests, meeting the qualifications in § 493.1449.² The technical supervisor is responsible for selecting the test methodology, verifying test procedures, establishing test performance characteristics, and establishing the quality control programme.² The technical supervisor evaluates the competency of all testing personnel using the six methods listed in § 493.1451(b)(8), including direct observation of routine patient test performance.² Performance of individuals responsible for high complexity testing is evaluated at least semiannually during the first year and at least annually thereafter, with reevaluation before reporting results whenever the methodology or instrumentation changes.²

General supervisors provide day-to-day supervision of testing personnel and reporting of results.² They must be accessible for on-site, telephone or electronic consultation at all times testing is performed.² Testing personnel must meet one of the routes in § 493.1489(b), which range from a medical degree to an associate degree in laboratory science to specified military laboratory training.² The laboratory must establish and follow written policies to assess employee and, where applicable, consultant competency.²

Personnel for moderate complexity testing

Where the laboratory’s test is categorized as moderate complexity, the director qualification routes in § 493.1405(b) apply. These include pathology board certification and a medical or podiatric degree with one year directing or supervising nonwaived testing and 20 CE credit hours. Doctoral, master’s and bachelor’s routes with specified nonwaived training and supervisory experience also apply.² Testing personnel qualify under § 493.1423, which reaches high school graduates with documented laboratory training covering the eight skill areas in § 493.1423(b)(6)(ii).² The same 28 December 2024 continuity provision appears for both roles.²

The report itself

The test report must identify the patient, name the laboratory location where the test was performed, and state the report date, the test performed, the specimen source where appropriate and the result.² Reference intervals determined by the performing laboratory must be available to the authorized person who ordered the test.² On request, the laboratory must make available to clients a list of its test methods and the performance specifications established or verified under § 493.1253.² Information affecting interpretation, such as test interferences, is provided on request.² Where a reported result is later found to be in error, the laboratory promptly notifies the ordering person, issues a corrected report and keeps duplicates of both.²

Questions people also ask

Does a laboratory-developed test need FDA clearance before a CLIA-certified laboratory reports results from it?

Part 493 addresses the laboratory’s certification and quality obligations. Under § 493.1253(b)(2), a test system not subject to FDA clearance or approval places the laboratory under the duty to establish performance specifications before reporting patient results, which indicates that the regulation contemplates such systems in use.¹ Test categorization for a system that is not commercially available is handled through a written request to PHS, forwarded to CDC.²

What is the difference between verifying and establishing performance specifications?

Verification applies to an unmodified FDA-cleared or approved test system and covers accuracy, precision and reportable range, plus confirmation that the manufacturer’s reference intervals suit the patient population.¹ Establishment applies to a modified system, a system outside FDA clearance or approval, and a system for which the manufacturer supplies no specifications. It covers the following.¹

• accuracy
• precision
• analytical sensitivity
• analytical specificity including interfering substances
• reportable range
• reference intervals
• any other characteristic required for test performance

How often must a laboratory director be physically present in the laboratory?

For both moderate and high complexity testing, the director must be on site at least once every six months, with at least four months between the two minimum visits. Each visit must be documented with evidence of director activities.² Directors may attend more frequently and must remain accessible for telephone or electronic consultation.² An individual may direct no more than five laboratories.²

What happens if a test method has no approved proficiency testing programme?

Enrollment in an approved programme is required for each specialty and subspecialty for which the laboratory seeks certification.² For tests the laboratory performs that are not included in subpart I, § 493.801(a)(2)(ii) requires the laboratory to establish and maintain the accuracy of its testing procedures in accordance with § 493.1236(c)(1).²

How long is a certificate of compliance valid?

A certificate of compliance is valid for no more than two years.² A laboratory seeking renewal completes and returns the renewal application to HHS 9 to 12 months before the certificate expires, and must continue to meet § 493.43, the fee requirement and the inspection requirement.²

Footnotes

1. 42 CFR 493.1253, Standard: Establishment and verification of performance specifications. https://www.ecfr.gov/current/title-42/chapter-IV/subchapter-G/part-493/subpart-K/section-493.1253 ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶ ↩⁷ ↩⁸ ↩⁹ ↩¹⁰ ↩¹¹

2. 42 CFR Part 493, Laboratory Requirements. https://www.ecfr.gov/current/title-42/chapter-IV/subchapter-G/part-493 ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶ ↩⁷ ↩⁸ ↩⁹ ↩¹⁰ ↩¹¹ ↩¹² ↩¹³ ↩¹⁴ ↩¹⁵ ↩¹⁶ ↩¹⁷ ↩¹⁸ ↩¹⁹ ↩²⁰ ↩²¹ ↩²² ↩²³ ↩²⁴ ↩²⁵ ↩²⁶ ↩²⁷ ↩²⁸ ↩²⁹ ↩³⁰ ↩³¹ ↩³² ↩³³ ↩³⁴ ↩³⁵ ↩³⁶ ↩³⁷ ↩³⁸ ↩³⁹ ↩⁴⁰ ↩⁴¹ ↩⁴² ↩⁴³ ↩⁴⁴ ↩⁴⁵ ↩⁴⁶ ↩⁴⁷ ↩⁴⁸ ↩⁴⁹ ↩⁵⁰ ↩⁵¹ ↩⁵² ↩⁵³ ↩⁵⁴ ↩⁵⁵ ↩⁵⁶ ↩⁵⁷ ↩⁵⁸ ↩⁵⁹ ↩⁶⁰ ↩⁶¹ ↩⁶² ↩⁶³ ↩⁶⁴