CMS Seeks Broad Stakeholder Input on CLIA Regulations, Signaling Potential Modernization of Current Lab Regulatory Scheme

On July 16, 2026, the Centers for Medicare & Medicaid Services (CMS) and the Centers for Disease Control and Prevention (CDC) announced that they are seeking public input on various issues relevant to the regulations implementing the Clinical Laboratory Improvements Amendments of 1988—which took effect in 1992 (“CLIA Regulations”).

The goal of the request for information (RFI) is to collect information that will help CMS decide what type of rule updates, if any, may be required to modernize the federal lab regulatory scheme through future rulemaking.

Significantly, the RFI seeks comments on issues relating to the validation of non-cleared or approved laboratory tests (commonly referred to as laboratory developed tests, or “LDTs”), which dovetails with certain issues with recently proposed legislation on the subject, such as H.R.8890 (Enhancing CLIA Act of 2026).

What You Need to Know

• Long-Standing Regulatory Framework: The CLIA Regulations, codified at 42 CFR part 493, have remained substantially unchanged, particularly with regard to many of their technical standards and conditions, since taking effect in 1992, at which time most of the technologies the RFI now asks stakeholders to address were not in use.
• Scope of Stakeholder Input: The RFI seeks comment on four major categories: (1) breath testing; (2) laboratory processes and procedures; (3) emergency preparedness, biosafety, biosecurity, and cybersecurity; and (4) specialty testing areas.
• Key Subcategories for Comment: Significant subcategories within the “laboratory processes and procedures” topic include performance and validation standards for LDTs, the use of artificial intelligence (AI) in result interpretation, and the regulation of “data only” facilities.
• Comment Deadline: Stakeholders wishing to comment must do so by September 14, 2026.

The Details

The RFI covers all aspects of the CLIA Regulations, with CMS and the CDC seeking input on (1) breath testing; (2) laboratory processes and procedures; (3) emergency preparedness, biosafety, biosecurity, and cybersecurity; and (4) specialty testing areas and in numerous subcategories. Stakeholders are invited to comment on how laboratory testing, and these areas in particular, have evolved since the CLIA Regulations were enacted.

This Insight summarizes key areas of the RFI, highlighting the significance of the proposed modernization effort for clinical laboratories and other affected stakeholders.

Background

As the RFI explains, Congress enacted CLIA, 42 U.S.C. 263a, on October 31, 1988, amending section 353 of the Public Health Service Act. CLIA requires all facilities that examine materials derived from the human body for purposes of providing information for the diagnosis, prevention, or treatment of any disease or impairment of, or the assessment of the health of, human beings to obtain a certificate from the U.S. Department of Health and Human Services (HHS). CLIA also requires such facilities to meet certain requirements, such as maintaining a quality assurance and quality control program that is adequate and appropriate for the validity and reliability of the laboratory examinations and other procedures of the laboratory, and maintaining laboratory personnel standards.

The CLIA Regulations specify the conditions and standards that a clinical laboratory must meet to achieve and maintain CLIA certification. The goal of CLIA, as commonly understood since its implementation, is to strengthen federal oversight of clinical laboratories while ensuring the accuracy and reliability of patient test results.

Acknowledging that laboratory technology and practices have changed significantly over the last three decades, CMS issued the RFI to seek broad input on practices for “which the CLIA regulations may need to be updated to better reflect current knowledge and advancements in laboratory testing.”

Questions and Topics for Comment

Breath Testing

The RFI notes that when the CLIA Regulations were promulgated in 1992, 57 Fed. Reg. 7002, breath testing had not yet been developed for clinical use. However, during the COVID-19 Public Health Emergency, researchers and manufacturers developed breath tests for COVID-19, demonstrating an increased interest in expanding their clinical application. Further, CMS has received inquiries regarding whether breath testing more broadly—including, for example, for cancer diagnosis, microbial identification, and gastrointestinal disorders—is subject to CLIA and its implementing regulations. Therefore, the RFI seeks input on the following: what types of breath tests are performed for clinical use and at what types of facilities; the methodologies and technologies associated with the use of breath tests; the collection, transport, and storage practices for breath tests; and the specific challenges connected with breath tests.

Laboratory Processes and Procedures

Pathology Specimen Retention. Section 493.1105(a)(7)(ii) currently requires that pathology specimen blocks be retained for a minimum period of two years. However, advancements in molecular diagnostics now enable laboratories to perform retrospective testing on tissues more than two years old. The RFI seeks information on the types of requests the laboratory receives for additional testing on pathology specimen blocks after the required two-year retention period, as well as the frequency.

Specimen Preparation & Personnel Qualifications. The RFI solicits public comment on the preanalytic practices currently employed by clinical laboratories, as well as the qualifications, education, experience, and training of personnel responsible for performing these activities. In particular, the RFI seeks input on how laboratories ensure that personnel who perform specimen preparation activities remain competent.

Suboptimal Specimens. The RFI seeks public comment on how labs handle the problem of being asked to test specimens that do not meet quality standards.

Performance Specifications for Non-FDA Tests. Current regulations require verifying performance specifications (accuracy, sensitivity, specificity, etc.) when introducing any unmodified Food and Drug Administration (FDA)-cleared or approved test system, and establishing performance specifications when introducing any test system that is not FDA-cleared or approved, or that is a modification to an FDA-cleared or approved test system (a/k/a an LDT). The RFI seeks input on how labs establish performance specifications for tests that are not FDA-cleared or approved, including tests that constitute modifications of FDA-cleared or approved tests, and asks the following specific questions:

• For tests that are not FDA-cleared or approved, including modifications of FDA-cleared or approved tests, what challenges does the laboratory encounter when establishing adequate performance specifications and appropriate acceptance criteria? (Specify the relevant test or procedure.)
• What testing methods (for example, toxicology and next-generation sequencing (NGS)) and/or specific applications of those methods (use of NGS to test for somatic or germline variants, minimal residual disease, methylation, bacterial resistance mutations, viral identification, or HLA matching) have unique performance characteristics that need to be established and are not already addressed in the CLIA Regulations or guidance? What are those performance characteristics (e.g., stability studies, carryover, internal standards, ionization, clinical validity)?
• How does the laboratory currently design, develop, and prepare reagents for tests developed in-house?
• What types of modifications does the laboratory commonly make to FDA-cleared or approved test systems?

Calibration Verification. Modern analyzers are factory-calibrated and non-adjustable (point-of-care tests). Current regulations, however, require specific calibration verification procedures. The RFI seeks input on technical challenges with manufacturer-calibrated devices.

Artificial Intelligence and Postanalytic Interpretation. Test systems increasingly use AI/software for interpretation (histopathology, genetic testing, etc.). The RFI seeks input on the use of advanced technology or AI-assisted interpretation in clinical laboratories and the testing process, including the following specific questions:

• How does the laboratory use software algorithms or AI tools in the postanalytic process?
• Under what circumstances are software functions, including certain AI tools, used for the interpretation of the results of a test? (For example, NGS, histocompatibility, and pharmacogenomics testing.)
• What roles do software functions, including certain AI tools, currently play in the interpretation of histopathology slides or results?
• What methods do laboratories use to verify the performance of the software functions (including image resolution accuracy and quality, and AI tools, as well as the performance of computers and monitors) used with a test system?
• Are there additional technology considerations for high-complexity tests, including, but not limited to, laboratory use of automation, laboratory use of cloud analytics, and laboratory use of AI, that CMS and the CDC should consider incorporating into the CLIA Regulations?

Data-Only Facilities. Facilities that only process analytical data or provide specialized data interpretation, such as medical device software, without any traditional “wet lab” activities, have emerged and become more common in the health care ecosystem. As such, the RFI seeks input on whether these types of operations should require CLIA certification. Of note, the general consensus, as informed by CMS’s guidance, is that “dry labs” or facilities that perform only data analysis of lab results are not CLIA-regulated facilities.

Presumably to help CMS determine whether some modification of the current state is needed, the RFI asks specifically: “What activities do data-only facilities perform to generate, or help to generate, test results and interpretations?”

Remote Competency Assessment. Prior to being dissolved by HHS in 2025, the Clinical Laboratory Improvement Advisory Committee (CLIAC) recommended allowing virtual assessments, which are particularly beneficial for rural laboratories. The RFI seeks input on remote technology use for competency evaluation.

Emergency Preparedness, Biosafety, Biosecurity, and Cybersecurity

Emergency Preparedness. A 2025 Inspector General Report found that independent labs lack emergency preparedness plans, which could pose a risk during pandemics or other disasters when labs need to maintain diagnostic testing capacity. The RFI solicits input on best practices and operational challenges associated with implementing a laboratory-specific emergency preparedness plan requirement.

Biosafety and Biosecurity. COVID-19 highlighted the need for proper biosafety training and protocols. The RFI requests input on challenges in handling infectious materials safely.

Cybersecurity. As clinical laboratories increasingly rely on digital systems and connected technologies—such as Laboratory Information System (LIS), Electronic Health Record (EHR) integration, automated diagnostic devices, and virtual or remote access to laboratory and patient data—new cybersecurity risks have emerged. The RFI seeks public comments on laboratory cybersecurity practices and experiences, including data protection protocols, user access verification, and incident response plans.

Specialty Testing Areas

Clinical Cytogenetics. The RFI seeks public comments on technical advancements in clinical cytogenetic testing, which involves chromosome abnormalities associated with congenital disorders and cancer. The RFI also requests input on clinical cytogenetics test procedures and technologies, as well as challenges.

Immunohematology. The RFI solicits public comments on technical advancements in immunohematology, an area of laboratory medicine involving the selection and preparation of blood and blood components for transfusion as well as the monitoring of those components following transfusion. The RFI asks for input on immunohematology practices and technologies; challenges (including operational challenges); and quality assurance issues with respect to electronic crossmatch.

Microbiology. There are no specific CLIA Regulations governing blood culture contamination (BCC) rates or mandating systematic monitoring and corrective action protocols, though CLIAC previously recommended updating regulations to require BCC monitoring. The RFI seeks input on best practices and challenges associated with such a requirement.

Impact on CLIA Regulations

Short-term (Next 6-12 months):

• There are no immediate changes because this is an RFI and not a proposed or final rule.
• The public will submit comments through September 2026.
• CMS/CDC will review feedback for planning purposes.

Medium-term (1-3 years):

• Formal notice-and-comment rulemaking on specific topics is possible, if not likely. Potential updates could address:
  • new verification and validation standards for both FDA-cleared and approved tests and LDTs;
  • the certification of “data-only” facilities;
  • when and how AI/software is used in laboratory testing;
  • emergency preparedness requirements;
  • cybersecurity standards;
  • new testing modalities (breath testing, NGS); and
  • remote competency assessment authorization.

Long-term Impact:

This RFI signals possible regulatory modernization. CLIA may evolve to include rules that:

• cover modern technologies (e.g., AI, cloud analytics, digital systems);
• provide more robust regulation of LDTs;
• address contemporary operational challenges (e.g., cybersecurity activities and measures, emergency response);
• regulate new and emerging specialties; and
• promote workflow flexibility (e.g., remote proficiency testing).

What Laboratories Should Do Now

Responses to the RFI may help CMS and the CDC in their task of updating existing CLIA Regulations through future notice and comment rulemaking; thus, the agencies are encouraging input from a wide variety of stakeholders. Therefore, laboratories and other affected stakeholders should do the following:

• Consider submitting comments to CMS describing your actual practices and challenges.
• Identify specific sections, subsections, and questions consistent with the structure of the RFI when responding.
• Ensure your responses to the RFI are received by September 14, 2026. Comments may be submitted by regular or express mail (refer to the RFI for addresses) or electronically at https://www.regulations.gov/docket/CMS-2026-2345. See Docket CMS-2026-2345 for published comments.
• Prepare for potential regulatory updates in emerging areas (AI, cybersecurity, and emergency preparedness).

* * * *

For additional information about the issues discussed in this Insight, please contact the attorney(s) listed on this page or the Epstein Becker Green Health Care and Life Sciences attorney who regularly handles your legal matters.

Epstein Becker Green Staff Attorney Ann W. Parks contributed to the preparation of this Insight.