[Federal Register Volume 91, Number 135 (Thursday, July 16, 2026)]
[Proposed Rules]
[Pages 43586-43591]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2026-14358]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Medicare & Medicaid Services

42 CFR Part 493

[CMS-3485-NC]
RIN 0938-AW01


Request for Information; Clinical Laboratory Improvement 
Amendments of 1988 (CLIA) Regulations

AGENCY: Centers for Medicare & Medicaid Services (CMS) and Centers for 
Disease Control and Prevention (CDC), Department of Health and Human 
Services (HHS).

ACTION: Request for information.

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SUMMARY: Clinical laboratory testing technology has advanced 
significantly since the Clinical Laboratory Improvement Amendments of 
1988 (CLIA) regulations were implemented in 1992. This request for 
information (RFI) seeks input from the public regarding various topics 
related to the CLIA regulations, including: breath testing; laboratory 
processes and procedures; emergency preparedness, biosafety and 
biosecurity, and cybersecurity; and specialty testing areas. Responses 
to this RFI may be used to help inform CMS and the CDC as to what types 
of action, if any, should be taken to update the existing CLIA 
regulations through future notice and comment rulemaking.

DATES: To be assured consideration, comments must be received at one of 
the addresses provided below, by September 14, 2026.

ADDRESSES: In commenting, refer to file code CMS-3485-NC.
    Comments, including mass comment submissions, must be submitted in 
one of the following three ways (please choose only one of the ways 
listed):
    1. Electronically. You may submit electronic comments on this 
regulation at https://www.regulations.gov/docket/CMS-2026-2345. Follow 
the ``Submit a comment'' instructions.
    2. By regular mail. You may mail written comments to the following 
address ONLY: Centers for Medicare & Medicaid Services, Department of 
Health and Human Services, Attention: CMS-3485-NC, P.O. Box 8016, 
Baltimore, MD 21244-8016.
    Please allow sufficient time for mailed comments to be received 
before the close of the comment period.
    3. By express or overnight mail. You may send written comments to 
the following address ONLY: Centers for Medicare & Medicaid Services, 
Department of Health and Human Services, Attention: CMS-3485-NC, Mail 
Stop C4-26-05, 7500 Security Boulevard, Baltimore, MD 21244-1850.
    For information on viewing public comments, see the beginning of 
the SUPPLEMENTARY INFORMATION section.

FOR FURTHER INFORMATION CONTACT: 
    Penny Keller at [email protected], 410-786-2035.
    Jake D. Bunn at [email protected], 404-498-4493.

SUPPLEMENTARY INFORMATION: 
    Inspection of Public Comments: All comments received before the 
close of the comment period are available for viewing by the public, 
including any personally identifiable or confidential business 
information that is included in a comment. We post all comments 
received before the close of the comment period on the following 
website as soon as possible after they have been received: https://www.regulations.gov. Follow the search instructions on that website to 
view public comments. CMS will not post on Regulations.gov public 
comments that make threats to individuals or institutions or suggest 
that the commenter will take actions to harm an individual. CMS 
continues to encourage individuals not to submit duplicative comments. 
We will post acceptable comments from multiple unique commenters even 
if the content is identical or nearly identical to other comments.

I. Background

    On October 31, 1988, Congress enacted the Clinical Laboratory 
Improvement Amendments of 1988 (CLIA) (Pub. L. 100-578), which amended 
section 353 of the Public Health Service Act (PHSA). 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 HHS. CLIA also 
requires such facilities to meet certain requirements such as 
maintaining a quality assurance and quality control program adequate 
and appropriate for the validity and reliability of the laboratory 
examinations and other procedures of the laboratory and maintaining 
laboratory personnel standards. The implementing regulations at 42 CFR 
part 493 specify, in part, the conditions and standards that a clinical 
laboratory must meet to achieve and maintain CLIA certification. These 
conditions and standards strengthen Federal oversight of clinical 
laboratories and help ensure the accuracy and reliability of patient 
test results.

II. Solicitation of Public Comments

    This RFI seeks public comments on various topics related to the 
CLIA regulations. CMS and the CDC are issuing this RFI to gather input 
from the public regarding the following topics related to the CLIA 
regulations: (A) breath testing; (B) laboratory processes and 
procedures; (C) emergency preparedness, biosafety and biosecurity, and 
cybersecurity; and (D) specialty testing areas. CMS, the CDC, 
interested parties, and State Agency surveyors identified the topics in 
this RFI as areas in which the CLIA regulations may need to be updated 
to better reflect current knowledge and advancements in laboratory 
testing. Commenters are encouraged to identify the specific section and 
question number(s) (for example, Section A. Breath Testing, Question 1; 
Section B. Laboratory Processes and Procedures, Subsection 2. Specimen 
Preparation Activities and Personnel, Question 2) addressed in each 
portion of their submission and to organize comments consistent with 
the

[[Page 43587]]

structure of this RFI. We encourage input from a wide variety of 
interested parties on the questions set forth in this RFI.

A. Breath Testing

    CMS and the CDC believe that testing using certain newer 
technologies may fall within the scope of CLIA and its implementing 
regulations because they may involve examination of ``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.'' For example, when the 
CLIA regulations were promulgated in 1992 (57 FR 7002),\1\ breath 
testing had not yet been developed for clinical use and was only 
utilized for purposes of law enforcement. However, during the SARS-CoV-
2 (COVID-19) Public Health Emergency (PHE), researchers and 
manufacturers developed breath tests for COVID-19, demonstrating an 
increased interest in expanding its clinical application. As breath 
testing is not specifically addressed in the current CLIA regulations, 
CMS has received inquiries regarding whether breath testing for cancer 
diagnosis, microbial identification, and gastrointestinal disorders is 
subject to CLIA and its implementing regulations.
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    \1\ Medicare, Medicaid and CLIA Programs; Regulations 
Implementing the Clinical Laboratory Improvement Amendments of 1988 
(CLIA) Final Rule with Comment Period (57 FR 7002, February 28, 
1992), available at https://tile.loc.gov/storage-services/service/ll/fedreg/fr057/fr057040/fr057040.pdf.
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    CMS and the CDC seek public comments on breath testing used in 
clinical settings to inform whether updates to the CLIA regulations 
should be considered. In addition, we seek input on the following 
specific questions:
    1. What breath tests are facilities performing for clinical use?
    2. What methodologies and technologies do facilities use in breath 
testing for clinical use?
    3. What type of facilities (such as hospitals, gastrointestinal 
clinics, and reference laboratories) perform breath testing for 
clinical use?
    4. How do facilities collect, transport, and store clinical breath 
specimens? What challenges, if any, are encountered?

B. Laboratory Processes and Procedures

1. Pathology Specimen Block Retention
    The CLIA regulatory requirement at Sec.  493.1105(a)(7)(ii) 
currently stipulates that pathology specimen blocks must be retained 
for a minimum period of 2 years. However, advancements in molecular 
diagnostics now enable laboratories to perform retrospective testing on 
tissues more than 2 years old.
    CMS and the CDC seek public comments on laboratories' experience 
with requests for additional testing on pathology specimen blocks 
beyond the required 2-year retention period. Specifically, we seek 
input on the following question:
    1. What types of requests does the laboratory receive for 
additional testing on pathology specimen blocks after the required 2-
year retention period, and how frequently does the laboratory receive 
them?
2. Specimen Preparation Activities and Personnel
    The preanalytic phase of laboratory testing encompasses all 
processes that occur before the analytical testing, including specimen 
collection, preparation, and handling. The scope of specimen 
preparation activities is broad, encompassing processes such as 
centrifuging, aliquoting, tissue processing, slide staining, 
inoculating culture plates, and extracting ribonucleic acid (RNA) and 
deoxyribonucleic acid (DNA). At Sec.  493.2, the definition of 
``laboratory'' provides that facilities only collecting or preparing 
specimens (or both) or only serving as a mailing service and not 
performing testing are not considered laboratories for CLIA 
certification purposes. Given the critical role that preanalytic 
processes play in ensuring accurate and reliable test results, and the 
potential impact of preanalytic errors on patient care, CMS and the CDC 
are soliciting public comment on the preanalytic practices currently 
employed by clinical laboratories, as well as the qualifications, 
education, and experience of personnel responsible for performing these 
activities. In addition, we seek input on the following specific 
questions:
    1. What activities does the laboratory consider to be part of 
specimen preparation (for example, centrifuging, aliquoting, loading on 
analyzers, adding chemicals for preparation, tissue processing, slide 
staining, inoculating culture plates, DNA/RNA extraction)?
    2. What is the education and experience of the personnel who 
perform specimen preparation activities for your laboratory?
    3. What types of training does the laboratory provide for the 
personnel who perform specimen preparation activities?
    4. How does the laboratory ensure that personnel who perform 
specimen preparation activities remain competent?
3. Suboptimal Specimens
    Section 493.1242(a) of the CLIA regulations requires laboratories 
to establish and follow written policies and procedures for specimen 
acceptability and rejection. Clinical laboratories sometimes receive 
specimens in suboptimal conditions that do not meet their specimen 
acceptability policies and procedures and are asked by providers to 
perform testing. CMS has received inquiries regarding the handling of 
suboptimal specimens.
    CMS and the CDC seek public comments on how laboratories address 
suboptimal specimens. In addition, we seek input on the following 
specific questions:
    1. What are the circumstances under which the laboratory tests 
suboptimal specimens?
    2. How often does your laboratory test suboptimal specimens 
annually?
    3. How does the laboratory document and report results from 
suboptimal specimens?
    4. How does the laboratory communicate with ordering providers 
regarding suboptimal specimens?
    5. What quality assurance measures does the laboratory apply to the 
testing of suboptimal specimens?
    6. What challenges does the laboratory face in managing suboptimal 
specimens while ensuring test result quality?
4. Establishment and Verification of Performance Specifications
    The CLIA regulatory requirement at Sec.  493.1253 requires 
laboratories to verify performance specifications when introducing any 
unmodified Food and Drug Administration (FDA)-cleared or approved test 
system, and to establish 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. The performance 
specifications required to be established at Sec.  493.1253(b)(2) 
include accuracy, precision, analytical sensitivity, analytical 
specificity to include interfering substances, reportable range of test 
results for the test system, reference intervals (normal values), and 
any other performance characteristics required for test performance. 
CMS has received inquiries regarding the performance specifications of 
tests that are not FDA-cleared or approved, including modifications to 
FDA-cleared or approved tests.

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    CMS and the CDC seek public comments on how laboratories establish 
performance specifications for tests that are not FDA-cleared or 
approved, including modifications of FDA-cleared or approved tests. In 
addition, we seek input on the following specific questions:
    1. 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 associated with such challenges.
    2.a. What testing methods (for example, toxicology and next-
generation sequencing (NGS)), and/or specific applications of those 
methods (for example, 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?
    2.b. What are those performance characteristics (for example, 
stability studies, carry-over, internal standards, ionization, and 
clinical validity)?
    3. How does the laboratory currently design, develop, and prepare 
reagents for tests developed in-house?
    4. What types of modifications does the laboratory commonly make to 
FDA-cleared or approved test systems?
5. Calibration Verification
    Calibration verification procedures are critical to ensuring the 
accuracy and reliability of clinical laboratory test systems. Section 
493.1255 requires laboratories performing nonwaived testing to 
substantiate the continued accuracy of their test systems throughout 
the laboratory's reportable range of results. Specifically, Sec.  
493.1255(b)(1) requires laboratories to follow the manufacturer's 
calibration verification instructions.
    Manufacturers design factory-calibrated, non-adjustable 
instruments, including closed systems and cartridge-based analyzers 
such as point-of-care test systems, with embedded reagents and 
calibration parameters that are locked at the time of manufacture. CMS 
has received inquiries regarding calibration verification for test 
systems that manufacturers entirely calibrate, and that end users 
cannot adjust.
    CMS and the CDC seek public comments on calibration verification 
practices for factory-calibrated, non-adjustable instruments. In 
addition, we seek input on the following specific question:
    1. What technical and operational challenges does the laboratory 
face when performing calibration verification on FDA-cleared or 
approved manufacturer-calibrated devices?
6. Postanalytic Interpretation and Use of Artificial Intelligence (AI)
    CMS has received multiple inquiries regarding which postanalytic 
activities CMS considers part of the testing process. Test systems are 
becoming increasingly complex and integrated with advanced technology 
and AI systems. Certain software and software functions are subject to 
regulation as medical devices under the Federal Food, Drug, and 
Cosmetic Act.
    As test systems become increasingly complex, CMS and the CDC seek 
public comments on the use of advanced technology or AI-assisted 
interpretation in clinical laboratories and the testing process. In 
addition, we seek input on the following specific questions:
    1. How does the laboratory use software algorithms or AI tools in 
the postanalytic process?
    2. 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.
    3. What roles do software functions, including certain AI tools, 
currently play in the interpretation of histopathology slides or 
results?
    4. 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?
    5. 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 
artificial intelligence, that CMS and the CDC should consider 
incorporating into the CLIA regulations?
7. Data-Only Facilities
    Section 493.2 of the CLIA regulations defines a ``laboratory'' as a 
facility for the biological, microbiological, serological, chemical, 
immunohematological, hematological, biophysical, cytological, 
pathological, or other examination of materials derived from the human 
body for the purpose of providing information for the diagnosis, 
prevention, or treatment of any disease or impairment of, or the 
assessment of the health of, human beings. In addition, Sec.  493.2 
defines ``distributive testing'' as laboratory testing performed on the 
same specimen, or an aliquot of it, that requires sharing it between 
two or more laboratories to obtain all data required to complete an 
interpretation or calculation necessary to provide a final reportable 
result for the originally ordered test. When such testing occurs at 
multiple locations with different CLIA certificates, CMS considers it 
distributive testing.
    Facilities that only process analytical data or provide specialized 
data interpretation, some of which may be manufacturers of medical 
device software, have emerged. CMS has received inquiries on whether 
these types of data-only facilities require a CLIA certificate. These 
inquiries have in part focused on facilities that review and interpret 
genetic data, digital images, and perform calculations of risk factors.
    CMS and the CDC seek public comments on data-only facilities. In 
addition, we seek input on the following question:
     What activities do data-only facilities perform to 
generate, or help to generate, test results and interpretations?
8. Remote Direct Observation Competency Assessment
    Sections 493.1413(b)(8)(i) and (iv) and 493.1451(b)(8)(i) and (iv) 
of the CLIA regulations include direct observation of routine patient 
test performance and instrument maintenance and function checks as part 
of the evaluation of testing personnel competency by the technical 
consultant or technical supervisor. CMS has received requests from 
laboratories to include remote technology solutions in their competency 
assessment processes. Interested parties have advocated for the use of 
virtual competency assessments, particularly noting that facilities in 
rural areas would benefit from such remote assessment capabilities. At 
its November 2024 meeting, the Clinical Laboratory Improvement Advisory 
Committee (CLIAC) recommended that CMS allow remote assessment to be 
used for the direct observation component of competency assessment.\2\ 
This recommendation included using both on-site and virtual access 
technology to assess laboratory personnel competency, especially in 
remote or rural areas where in-person assessments are difficult or 
expensive.
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    \2\ CLIAC November 2024 Meeting Summary, https://www.cdc.gov/cliac/php/meetings/index.html#cc-widget-e3e3.
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    CMS and the CDC seek public comments, including evidence,

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research, and trends on the use of remote technology to conduct the 
direct observation component of competency assessments for laboratory 
personnel. In addition, we seek input on the following specific 
questions:
    1. How does the laboratory currently use remote direct observation 
for competency assessment?
    2. What types of devices (for example, smartphones, tablets, 
virtual reality devices/glasses, and dedicated video systems) does the 
laboratory currently use for remote direct observation for competency 
assessment?
    3. What challenges or limitations does the laboratory encounter 
with remote direct observation for competency assessment?

C. Emergency Preparedness, Biosafety and Biosecurity, and Cybersecurity

1. Emergency Preparedness
    In 2016, CMS issued the Medicare and Medicaid Programs; Emergency 
Preparedness Requirements for Medicare and Medicaid Participating 
Providers and Suppliers final rule,\3\ which established national 
emergency preparedness requirements for certain healthcare provider 
types to ensure adequate planning for natural disasters, human-caused 
disasters, facility emergencies, and emerging infectious diseases. 
However, this rule did not include CLIA-certified independent 
laboratories in its scope.
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    \3\ Medicare and Medicaid Programs; Emergency Preparedness 
Requirements for Medicare and Medicaid Participating Providers and 
Suppliers Final Rule, 81 FR 63860 (September 16, 2016), available at 
https://www.federalregister.gov/documents/2016/09/16/2016-21404/medicare-and-medicaid-programs-emergency-preparedness-requirements-for-medicare-and-medicaid.
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    A 2025 Office of Inspector General (OIG) Report recommended that 
CMS consider requiring independent laboratories that participate in 
Medicare to have emergency preparedness plans to better ensure that 
Medicare enrollees have access to diagnostic testing related to an 
emerging infectious disease or a biological toxin in the event of a 
future PHE.\4\ CLIA and its implementing regulations encompass a broad 
spectrum of laboratories, ranging from physician offices to large 
reference laboratories. CLIA regulations apply to laboratories, as 
defined at Sec.  493.2, regardless of their Medicare participation.
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    \4\ U.S. Department of Health and Human Services, Office of 
Inspector General. By Requiring Emergency Preparedness Plans for 
Independent Labs, CMS Could Better Ensure That Medicare Enrollees 
Have Access to Infectious-Disease Diagnostic Testing During a Public 
Health Emergency, OIG Report. 2025, available at https://oig.hhs.gov/reports/all/2025/by-requiring-emergency-preparedness-plans-for-independent-labs-cms-could-better-ensure-that-medicare-enrollees-have-access-toinfectious-disease-diagnostic-testing-during-a-public-health-emergency/.
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    CMS and the CDC seek public comments on how laboratories prepare 
for emergencies and any associated operational challenges. In addition, 
we seek input on the following specific questions:
    1. What are the best practices for laboratory emergency 
preparedness? Indicate the type of laboratory, for example, hospital-
based or independent laboratory.
    2. What challenges does the laboratory face in maintaining 
operations during emergencies such as natural and human-caused 
disasters, facility emergencies, and emerging infectious diseases?
    3. What elements does the laboratory include in its current 
emergency preparedness plans and protocols?
    4. What lessons has the laboratory learned from recent emergency 
situations (for example, natural disasters, pandemics, and power 
outages)?
    2. Biosafety and Biosecurity
    The CLIA regulatory requirement at Sec.  493.1101 requires 
laboratories to, among other things, establish appropriate safety 
procedures and comply with applicable Federal, State, and local 
requirements. Sections 493.1407(e)(2) and 493.1445(e)(2) assign 
laboratory directors the responsibility for ensuring that physical 
plant and environmental conditions provide a safe environment in which 
employees are protected from physical, chemical, and biological 
hazards.
    During the COVID-19 PHE, the CDC provided comprehensive guidance on 
biosafety and biosecurity protocols, risk assessments, and safety 
practices for laboratory personnel handling infectious materials.\5\ 
This guidance highlighted the essential role of proper biosafety and 
biosecurity training in ensuring that laboratory personnel could safely 
conduct testing procedures while minimizing risks to themselves, their 
colleagues, and the broader community. This training was essential at 
the beginning of the COVID-19 PHE, when patient testing volumes and 
operational demands increased, along with exposure risks for personnel. 
Throughout the COVID-19 PHE, the CDC received numerous inquiries from 
laboratories regarding biosafety and biosecurity knowledge and 
training.
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    \5\ Centers for Disease Control and Prevention (CDC), Laboratory 
Biosafety Guidelines for Working with SARS-CoV-2. U.S. Department of 
Health and Human Services, https://www.cdc.gov/covid/php/lab/index.html
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    CMS and the CDC seek public comments on biosafety and biosecurity 
protocols, risk assessments, and safety practices for laboratory 
personnel handling infectious materials. Respondents should not include 
any information that might be considered proprietary or confidential. 
In addition, we seek input on the following specific questions:
    1. What challenges does the laboratory face in biosafety and 
biosecurity?
    2. What elements or best practices does the laboratory include in 
its current biosafety and biosecurity plans and protocols?
    3. How does the laboratory train personnel on biosafety and 
biosecurity plans and protocols?
    3. Cybersecurity
    Cybersecurity threats across the healthcare sector have expanded in 
both scope and severity.\6\ 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. 
Various HHS agencies have a role in cybersecurity.
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    \6\ U.S. Department of Health and Human Services, Office for 
Civil Rights (OCR), Breach Portal: Notice to the Secretary of HHS--
Breach of Unsecured Protected Health Information. https://ocrportal.hhs.gov/ocr/breach/breach_report.jsf.
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    CMS and the CDC seek public comments on laboratory cybersecurity 
practices and experiences. Respondents should not include any 
information that might be considered proprietary or confidential. In 
addition, we seek input on the following specific questions:
    1. What cybersecurity protocols/policies does the laboratory have 
in place to protect patient data and laboratory operations?
    1.a. What is the frequency and process you follow to verify new or 
existing user identity and access requirements?
    1.b. Are individuals, entities, or both outside the U.S. and its 
Territories ever allowed to access your lab systems that contain 
personal information? If so, when and under what conditions?
    1.c. How does your laboratory system(s) restrict ports and/or 
internet protocol (IP) addresses used to access the environment?
    1.d. What elements are included in your cybersecurity incident 
response plan?
    2. What challenges or experiences has the laboratory faced in 
maintaining cybersecurity?

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    3. Which laboratory job position(s) is responsible for 
cybersecurity in the laboratory?
    4. How does the laboratory train personnel on cybersecurity?

D. Specialty Testing Areas

1. General
    CMS has received inquiries about adding additional specialties to 
the CLIA regulations, including, but not limited to, Mohs testing, 
andrology, and molecular testing.
    Given the rapid advancements in laboratory medicine, diagnostic 
technologies, and clinical practice patterns, CMS and the CDC are 
seeking public comments on operational challenges that laboratories 
encounter with specialties or subspecialties that are governed by the 
current CLIA regulations. In addition, we seek input on the following 
specific questions:
    1. What specific challenges or limitations, if any, does your 
laboratory currently experience with the test specialty and 
subspecialty categories in the CLIA regulations? For example, are there 
areas where existing CLIA test specialty and subspecialty categories 
could be revised to better reflect current laboratory testing 
practices?
    2. Are there additional specialties or subspecialties that CMS and 
the CDC should consider incorporating into the CLIA regulations to 
ensure comprehensive oversight of laboratory testing as specialties 
evolve? Provide evidence-based rationale supporting their inclusion, 
including considerations related to patient safety, testing complexity, 
and public health impact.
    2. Clinical Cytogenetics
    If a laboratory provides services in the specialty of clinical 
cytogenetics, in addition to requirements in other subparts of Part 
493, the laboratory must meet the requirements set forth in Sec. Sec.  
493.1225, 493.1230 through 493.1256, 493.1276, and 493.1281 through 
493.1299 of the CLIA regulations.
    Clinical cytogenetics provides genetic testing for chromosome 
abnormalities associated with congenital disorders and cancer. 
Laboratories employ both conventional cytogenetic and molecular 
cytogenomic approaches, including fluorescence in situ hybridization 
(FISH), to analyze genomic abnormalities at chromosomal and 
subchromosomal levels. Cytogenetic test results are important in 
managing patients with constitutional genetic conditions and cancer, as 
well as providing risk assessments for genetic counseling.\7\ Over the 
last 30 years, the field of clinical cytogenetics has seen significant 
technological advances, including molecular testing.\8\
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    \7\ National Institute of Health (NIH), National Library of 
Medicine, Muhammad Zubair, et.al., Genetics, Cytogenetic Testing and 
Conventional Karyotype, https://www.ncbi.nlm.nih.gov/books/NBK563293/.
    \8\ Anniker Biliard, Advances in Cytogenetic Technologies, types 
and their Applications, Perspective, J Clin Exp Oncol, Vol: 13 
Issue:2; https://www.scitechnol.com/peer-review/advances-in-
cytogenetic-technologies-types-and-their-applications-
uNFB.php?article_id=26372#:~:text=Fluorescence%20In%20Situ%20Hybridiz
ation%20(FISH,and%20studying%20complex%20genomic%20rearrangements.
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    CMS and the CDC seek public comments on technical advancements in 
clinical cytogenetic testing. In addition, we seek input on the 
following specific questions:
    1. What clinical cytogenetics test procedures and technologies does 
the laboratory currently use?
    2. What, if any, challenges does the laboratory face with existing 
CLIA regulations applicable to clinical cytogenetics?
    3. Immunohematology
    Immunohematology is an area of laboratory medicine that involves 
the selection and preparation of blood and blood components for 
transfusion as well as the monitoring of those components following 
transfusion.\9\ Electronic crossmatching systems use computer 
algorithms to compare patient blood type information and antibody 
screening results with donor blood characteristics stored in Blood 
Establishment Computer Systems (BECS). The distinction between 
traditional serologic crossmatching and electronic crossmatching 
represents a fundamental shift in laboratory methodology. Serologic 
crossmatching involves the physical mixing of a patient specimen with 
donor red blood cells to directly test for compatibility reactions. 
Electronic crossmatching, by contrast, relies on validated computer 
systems that must receive FDA clearance, for which laboratories must 
verify performance specifications, with qualified technologists 
reviewing and approving all results despite the automated nature of the 
compatibility determination.\10\ Since the CLIA regulations were 
promulgated, the field of immunohematology testing has seen significant 
medical and technological advancements.\11\
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    \9\ National Institute of Health (NIH), National Library of 
Medicine, Edward C C Wong, Blood banking/immunohematology: special 
relevance to pediatric patients, Pediatr Clin North Am, 2013 
Dec;60(6):1541-68; https://pubmed.ncbi.nlm.nih.gov/24237987/.
    \10\ Food and Drug Administration (FDA), ``Computer Crossmatch'' 
(Computerized Analysis of the Compatibility between the Donor's Cell 
Type and the Recipient's Serum or Plasma Type); FDA, https://www.fda.gov/regulatory-information/search-fda-guidance-documents/computer-crossmatch-computerized-analysis-compatibility-between-donors-cell-type-and-recipients.
    \11\ National Institute of Health (NIH), National Library of 
Medicine, Fernanda Morelati, et.al., New technologies in 
immunohaematology; https://pmc.ncbi.nlm.nih.gov/articles/PMC2535883/#sec8.
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    CMS and the CDC seek public comments on technical advancements in 
immunohematology. In addition, we seek input on the following specific 
questions:
    1. What immunohematology practices and technologies does the 
laboratory currently use?
    2. What, if any, challenges does the laboratory face with existing 
CLIA regulations for immunohematology?
    3. What operational challenges does the laboratory face with 
electronic crossmatches?
    4. What type of quality assurance issues does the laboratory 
encounter in electronic crossmatch compared to the traditional 
serologic crossmatch?
    4. Microbiology
    Blood culture contamination (BCC) represents a significant quality 
concern within microbiology specialty testing that directly impacts 
patient care outcomes, healthcare costs, and antimicrobial stewardship 
efforts. Contaminated blood cultures can lead to false-positive 
results, resulting in unnecessary antimicrobial therapy, extended 
hospital stays, additional diagnostic procedures, and increased 
healthcare expenditures. Furthermore, high contamination rates may mask 
true bacteremia cases and compromise the laboratory's ability to 
provide accurate diagnostic information to clinicians.
    There are no specific CLIA regulations governing BCC rates or 
mandating systematic monitoring and corrective action protocols. At its 
November 2023 meeting, CLIAC recommended updating the CLIA regulations 
to include BCC rate monitoring within the laboratory quality management 
system.\12\
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    \12\ CLIAC November 2023 Meeting Summary, https://www.cdc.gov/cliac/php/meetings/index.html#cc-widget-e3e3.
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    Considering the critical nature of blood culture testing in 
diagnosing life-threatening infections, CMS and the CDC seek public 
comments on how laboratories monitor BCC rates. In addition, we seek 
input on the following specific questions:
    1. What best practices has the laboratory implemented to reduce and 
monitor BCC?
    2. What challenges does the laboratory face in maintaining low 
blood culture contamination rates?

[[Page 43591]]

III. Collection of Information Requirements

    This is an RFI only. In accordance with the implementing 
regulations of the Paperwork Reduction Act of 1995 (PRA), specifically 
5 CFR 1320.3(h)(4), this general solicitation is exempt from the PRA. 
Facts or opinions submitted in response to general solicitations of 
comments from the public, published in the Federal Register or other 
publications, regardless of the form or format thereof, provided that 
no person is required to supply specific information pertaining to the 
commenter, other than that necessary for self-identification, as a 
condition of the agency's full consideration, are not generally 
considered information collections and therefore not subject to the 
PRA.
    This RFI is issued solely for information and planning purposes; it 
does not constitute a Request for Proposal (RFP), applications, 
proposal abstracts, or quotations. This RFI does not commit the U.S. 
Government to contract for any supplies or services or make a grant 
award. Further, we are not seeking proposals through this RFI and will 
not accept unsolicited proposals. Responders are advised that the U.S. 
Government will not pay for any information or administrative costs 
incurred in response to this RFI; all costs associated with responding 
to this RFI will be solely at the interested party's expense. We note 
that not responding to this RFI does not preclude participation in any 
future procurement, if conducted. It is the responsibility of the 
potential responders to monitor this RFI announcement for additional 
information pertaining to this request. In addition, we note that CMS 
will not respond to questions about the policy issues raised in this 
RFI.
    We will actively consider all input as we develop future regulatory 
proposals or future subregulatory policy guidance. We may or may not 
choose to contact individual responders. Such communications would be 
for the sole purpose of clarifying statements in the responders' 
written responses. Contractor support personnel may be used to review 
responses to this RFI. Responses to this notice are not offers and 
cannot be accepted by the U.S. Government to form a binding contract or 
issue a grant. Information obtained as a result of this RFI may be used 
by the U.S. Government for program planning on a non-attribution basis. 
Respondents should not include any information that might be considered 
proprietary or confidential. This RFI should not be construed as a 
commitment or authorization to incur cost for which reimbursement would 
be required or sought. All submissions become U.S. Government property 
and will not be returned. In addition, we may publicly post the public 
comments received, or a summary of those public comments.
    Mehmet Oz, Administrator of the Centers for Medicare & Medicaid 
Services, approved this document on July 8, 2026.
    Jay Bhattacharya, MD, Ph.D., Senior Official Carrying out the 
Delegable Duties of the Centers for Disease Control and Prevention 
Director, approved this document on July 13, 2026.

Robert F. Kennedy, Jr.,
Secretary, Department of Health and Human Services.
[FR Doc. 2026-14358 Filed 7-15-26; 8:45 am]
BILLING CODE 4169-69-P