[Federal Register Volume 87, Number 131 (Monday, July 11, 2022)]
[Rules and Regulations]
[Pages 41194-41242]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-14513]



[[Page 41193]]

Vol. 87

Monday,

No. 131

July 11, 2022

Part II





Department of Health and Human Services





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Centers for Medicare & Medicaid Services





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42 CFR Part 493





Clinical Laboratory Improvement Amendments of 1988 (CLIA) Proficiency 
Testing Regulations Related to Analytes and Acceptable Performance

  Federal Register / Vol. 87 , No. 131 / Monday, July 11, 2022 / Rules 
and Regulations  

[[Page 41194]]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Medicare & Medicaid Services

42 CFR Part 493

[CMS-3355-F]
RIN 0938-AT55


Clinical Laboratory Improvement Amendments of 1988 (CLIA) 
Proficiency Testing Regulations Related to Analytes and Acceptable 
Performance

AGENCY: Centers for Medicare & Medicaid Services (CMS), HHS; Centers 
for Disease Control and Prevention (CDC), HHS.

ACTION: Final rule.

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SUMMARY: This final rule updates proficiency testing (PT) regulations 
under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) to 
address current analytes (that is, substances or constituents for which 
the laboratory conducts testing) and newer technologies. This final 
rule also makes technical changes to PT referral regulations to better 
align them with the CLIA statute.

DATES: Effective August 10, 2022, except for the amendments to 
Sec. Sec.  493.2 and 493.801 through 493.959 (amendatory instructions 2 
and 5 through 21), which are effective July 11, 2024.

FOR FURTHER INFORMATION CONTACT: Sarah Bennett, CMS, (410) 786-3531; or 
Nancy Anderson, CDC, (404) 498-2741.

SUPPLEMENTARY INFORMATION: 

I. Background

    On October 31, 1988, Congress enacted the Clinical Laboratory 
Improvement Amendments of 1988 (Pub. L. 100-578) (CLIA '88), codified 
at 42 U.S.C. 263a, to ensure the accuracy and reliability of testing in 
all laboratories, including, but not limited to, those that participate 
in Medicare and Medicaid, that test human specimens for the purpose of 
providing information for the diagnosis, prevention, or treatment of 
any disease or impairment, or the assessment of health, of human 
beings. The Secretary established the initial regulations implementing 
CLIA on February 28, 1992 at 42 CFR part 493 (57 FR 7002). Those 
regulations required laboratories conducting moderate or high-
complexity testing to enroll in an approved proficiency testing (PT) 
program for each specialty, subspecialty, and analyte or test for which 
the laboratory is certified under CLIA. PT referral was further 
addressed by enactment of the Taking Essential Steps for Testing Act of 
2012 (Pub. L. 112-202, December 4, 2012) (TEST Act) and our 
implementing regulations (79 FR 25435 and 79 FR 27105). As of January 
2020, approximately 35,967 CLIA-certified laboratories were required to 
enroll in a U.S. Department of Health and Human Services (HHS)-approved 
PT program and comply with the PT regulations.
    Participation in PT is required under the CLIA statute for 
laboratories that perform moderate or high complexity testing. PT 
evaluates a laboratory's performance by testing unknown samples just as 
it would test patient samples. An HHS-approved PT program sends unknown 
samples to a laboratory for analysis. After testing, the laboratory 
reports its results to the PT program. The program grades the results 
using the CLIA grading criteria and provides the laboratory with its 
scores. PT is crucial to maintaining the quality of laboratory testing 
because it independently verifies the accuracy and reliability of 
laboratory testing, including the competency of testing personnel.
    Testing has evolved significantly since 1992, and today's 
technology is more accurate and precise than the methods used when the 
PT regulations became effective in 1994. In addition, many tests for 
analytes for which PT was not initially required are now in routine 
clinical use. For example, tests for troponins, which are used to 
diagnose myocardial infarction, and the hemoglobin A1c test commonly 
used to monitor glycemic control in persons with diabetes were not 
routinely performed prior to 1992. Recognizing these changes, we 
proposed revisions to update the existing PT regulations in a proposed 
rule entitled, ``Clinical Laboratory Improvement Amendments of 1988 
(CLIA) Proficiency Testing Regulations Related to Analytes and 
Acceptable Performance'', published in the February 4, 2019 Federal 
Register (84 FR 1536) (hereinafter the proposed rule).
    Generally, a final rule must be issued within 3 years of publishing 
a proposed rule, except under exceptional circumstances. As discussed 
in a notice entitled, ``Clinical Laboratory Improvement Amendments of 
1988 (CLIA) Proficiency Testing Regulations Related to Analytes and 
Acceptable Performance; Extension of Timeline for Publication of Final 
Rule'', published in the January 19, 2022, Federal Register (87 FR 
2736) (hereinafter the notice of extension), we could not meet the 
February 4, 2022 deadline due to the necessary reallocation of 
resources to respond to the COVID-19 public health emergency. 
Therefore, in the notice of extension, we announced an extension of the 
timeline to publish the final rule by 1 year until February 4, 2023.
    As part of the process for developing the proposed rule, HHS 
solicited input from the Clinical Laboratory Improvement Advisory 
Committee (CLIAC), the official Federal advisory committee charged with 
advising HHS regarding appropriate regulatory standards for ensuring 
accuracy, reliability, and timeliness of laboratory testing. Taking 
CLIAC's recommendations into account, CMS and CDC collaborated to 
develop a process to revise the list of required PT analytes listed in 
subpart I to determine which analytes should be retained, which should 
be deleted, and which analytes not currently listed in subpart I should 
be added to the regulations. Following the data-driven process and 
step-wise criteria used to select the candidate analytes to be included 
in the proposed rule, CMS and CDC sought feedback from PT programs on 
the following topics: current PT program practices using ``peer 
grouping'' to determine target values; the potential to include new 
analytes as required PT; the mechanism for grading current analytes; 
possible changes to the criteria for acceptable performance; and 
potential changes to microbiology subspecialties, including the 
replacement of the types of service as outlined currently at Sec. Sec.  
493.911(a), 493.913(a), 493.915(a), 493.917(a) and 493.919(a), with the 
proposed categories of required PT for each microbiology subspecialty 
at the above citations and the replacement of the list of specific 
organisms for each subspecialty with a proposed list of types of 
microorganisms.
    Based on empirical data and clinical relevance, CMS and CDC next 
worked to determine or revise the acceptance limits (ALs) (as defined 
in Sec.  493.2) for new and existing required analytes, respectively. 
Whenever possible, we proposed ALs as percentages. For each analyte, PT 
programs voluntarily provided data simulations using real PT data as a 
means of pilot testing our potential ALs. As stated in the proposed 
rule, ALs are intended to be used for scoring PT performance by PT 
programs and are not intended to be used by individual laboratories to 
satisfy the requirement at Sec.  493.1253(b) to establish performance 
specifications.

II. Provisions of the Proposed Regulations

    The proposed rule, if finalized, would amend the definitions and PT

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requirements in subpart A--General Provisions, Sec.  493.2 Definitions; 
subpart H--Participation in Proficiency Testing for Laboratories 
Performing Nonwaived Testing; and subpart I--Proficiency Testing 
Programs for Nonwaived Testing in the CLIA regulations.

A. Proposed Changes to Microbiology PT

1. Categories of Testing
    Subpart I of the CLIA regulations includes PT requirements for each 
subspecialty of microbiology, Sec. Sec.  493.911 through 493.919, which 
describe ``Types of services offered by laboratories'' for each 
subspecialty. In addition, since the regulations do not specify 
required analytes for microbiology as they do for other specialties, 
they include descriptions of levels or extents (for example, 
identification to the genus level only, identification to the genus and 
species level) used to determine the type of laboratory for PT 
purposes. CLIAC discussed the usefulness and limitations of the types 
of services listed in subpart I in helping laboratories enroll properly 
or in helping surveyors conduct laboratory inspections. It was noted 
that the types of services listed in subpart I do not allow for 
reporting growth or no growth, presence or absence, or presumptive 
identification of microorganisms on PT samples, which are common ways 
that physician office laboratories report patient results. CLIAC 
suggested revision of the regulations to include broad categories for 
the types of PT required for each microbiology subspecialty to allow 
flexibility for the inclusion of new technologies.
    After deliberation, CLIAC made the following recommendations:
     A system for categorizing types of service should be 
maintained in the regulations to help laboratories determine what PT 
they need to perform and assist surveyors in monitoring PT performance 
and patient testing.
     The regulations should include four categories of testing 
for each microbiology subspecialty, as applicable: stain(s), 
susceptibility and resistance testing, antigen and/or toxin detection, 
and microbial identification or detection.
    Based on these recommendations, we conducted a review of the PT 
modules offered by HHS-approved PT programs and consulted with CDC 
microbiology subject matter experts, who concurred that not all four 
recommended categories above are applicable to each microbiology 
subspecialty nor do PT programs have PT available for each category. If 
at some point in the future PT becomes available, we may propose to 
include additional categories of testing for microbiology 
subspecialties in future rulemaking. Based on these recommendations and 
our review, we proposed to modify Sec. Sec.  493.911 through 493.919 to 
remove the types of services listed for each microbiology subspecialty 
and to add the recommended categories of testing (that is, replace the 
list with broader categories of organisms) for each microbiology 
subspecialty as described in the bullets below. We believe that the 
revised microbiology PT regulations would better reflect current 
practices in microbiology.
    ++ Section 493.911(a): For bacteriology, we proposed that the 
categories required include, as applicable: Gram stain including 
bacterial morphology; direct bacterial antigen detection; bacterial 
toxin detection; detection and identification of bacteria which 
includes either: detection of growth or no growth in culture media or 
identification of bacteria to the highest level that the laboratory 
reports results on patient specimens; and antimicrobial susceptibility 
or resistance testing on select bacteria.
    ++ Section 493.911(a)(3): We proposed that the bacteriology annual 
PT program content described must include representatives of the 
following major groups of medically important aerobic and anaerobic 
bacteria if appropriate for the sample sources: Gram-negative bacilli; 
Gram-positive bacilli; Gram-negative cocci; and Gram-positive cocci.
    ++ Section 493.913(a): For mycobacteriology, we proposed that the 
categories for which PT is required include, as applicable: acid-fast 
stain; detection and identification of mycobacteria which includes one 
of the following: detection of growth or no growth in culture media or 
identification of mycobacteria; and antimycobacterial susceptibility or 
resistance testing.
    ++ Section 493.913(a)(3): For mycobacteriology, we proposed that 
the annual program content must include Mycobacterium tuberculosis 
complex and Mycobacterium other than tuberculosis (MOTT), if 
appropriate for the sample sources.
    ++ Section 493.915(a): For mycology, we proposed the categories for 
which PT is required include, as applicable: direct fungal antigen 
detection; detection and identification of fungi and aerobic 
actinomycetes which included one of the following: detection of growth 
or no growth in culture media or identification of fungi and aerobic 
actinomycetes; and antifungal susceptibility or resistance testing.
    ++ Section 493.915(a)(3): We proposed that annual program content 
must include the following major groups of medically important fungi 
and aerobic actinomycetes if appropriate for the sample sources: yeast 
or yeast-like organisms; molds that include dematiaceous fungi, 
dermatophytes, dimorphic fungi, hyaline hyphomycetes, and mucormycetes; 
and aerobic actinomycetes.
    ++ Section 493.917(a): For parasitology, we proposed requiring PT 
for direct parasite antigen detection and detection and identification 
of parasites.
    ++ Section 493.917(a)(3): We proposed that the annual program 
content must include intestinal parasites and blood and tissue 
parasites, if appropriate for the sample source.
    ++ Section 493.919(a): For virology, we proposed requiring PT, as 
applicable, for viral antigen detection; detection and identification 
of viruses; and antiviral susceptibility or resistance testing.
    ++ Section 493.919(a)(3): We proposed that the annual program 
content must include respiratory viruses, herpes viruses, enterovirus, 
and intestinal viruses, if appropriate for the sample source.
    We proposed revising the requirements for evaluating a laboratory's 
performance at Sec. Sec.  493.911(b) through 493.919(b) to be 
consistent with these categories. We did not propose to include antigen 
and toxin detection in the mycobacteriology subspecialty because no PT 
program currently offers applicable PT modules. We did not propose to 
include stains and antiparasitic susceptibility or resistance testing 
in the subspecialty of parasitology because no PT program offers 
applicable PT modules. We invited the public to comment on these 
proposals and specifically on the proposed categories of testing for 
the subspecialties listed above. We stated that if public comments 
indicate that applicable PT modules are available for antigen and toxin 
detection or stains and antiparasitic susceptibility or resistance 
testing, we may finalize their inclusion in the final rule, as 
applicable. If PT becomes available at some point in the future for 
mycobacteriology antigen and toxin detection testing, and stains and 
antiparasitic susceptibility or resistance testing, we may propose to 
include this category of testing for PT in future rulemaking. We 
summarize and respond to the public comments on these proposals and 
summarize our final policies in section III.E. of this final rule.

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    ++ Sections 493.911(b)(1), 493.913(b)(1), 493.915(b)(1), 
493.917(b)(1), and 493.919(b)(1): We proposed amending these provisions 
to clarify that to achieve consensus, PT programs must attempt to grade 
using both participant and referee laboratories \1\ before determining 
that the sample is ungradable. We believe that this change will enhance 
consistency among the PT programs when grading samples. The current 
regulations noted above allow for scoring either with participants or 
with referees before calling a sample ungradable. We summarize and 
respond to the public comments we received on these proposals and 
summarize our final policies in section III.D. of this final rule.
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    \1\ https://www.ecfr.gov/current/title-42/chapter-IV/subchapter-G/part-493#493.2.
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2. Major Groups of Microorganisms
    In the proposed rule (84 FR 1536, 1538), we proposed to remove the 
lists of specific example organisms from each microbiology subspecialty 
and add a more general list of organisms. This change clarifies that PT 
programs are able to be flexible in selecting which samples to provide 
to laboratories for PT, especially as new organisms are identified as 
being clinically important.
    Each subspecialty of microbiology, Sec. Sec.  493.911 through 
493.919, currently includes a list of the types of microorganisms that 
might be included in an HHS-approved PT program over time. Several PT 
programs have suggested to HHS that the regulations should include a 
more general list of types of organisms that must be included in 
required PT instead of a specific list. CLIAC considered whether there 
needs to be a more general list of organisms in the regulations to 
ensure a variety of challenges are offered over the course of the year. 
Following their deliberation, CLIAC made the following recommendation:
     Require PT for a general list of types of organisms in 
each subspecialty. For example, in bacteriology, the groups listed 
should include Gram-negative bacilli, Gram-positive bacilli, Gram-
negative cocci, and Gram-positive cocci.
    Generally, we have found that PT programs include only those 
organisms listed in the current regulations, and do not include 
additional organisms outside the current regulatory list. By 
restructuring to a more general list of organisms, it will be more 
apparent that PT programs are able to be flexible in selecting which 
samples to provide to laboratories for PT, especially as new organisms 
are identified as being clinically important. Therefore, we proposed to 
remove the lists of specific example organisms from each microbiology 
subspecialty, Sec. Sec.  493.911 through 493.919, and to add the 
following list of types of organisms to each.
    ++ Section 493.911(a)(3): For bacteriology, we proposed that the 
annual program content must include representatives of the following 
major groups of medically important aerobic and anaerobic bacteria if 
appropriate for the sample sources: Gram-negative bacilli; Gram-
positive bacilli; Gram-negative cocci; and Gram-positive cocci. The 
more general list of types of organisms will continue to cover the six 
major groups of bacteria currently listed in the regulations.
    ++ Section 493.913(a)(3): For mycobacteriology, we proposed that 
the annual program content must include Mycobacterium tuberculosis 
complex and Mycobacterium other than tuberculosis (MOTT), if 
appropriate for the sample sources.
    ++ Section 493.915(a)(3): For mycology, we proposed that the annual 
program content must include the following major groups of medically 
important fungi and aerobic actinomycetes if appropriate for the sample 
sources: yeast or yeast-like organisms; molds that include dematiaceous 
fungi, dermatophytes, dimorphic fungi, hyaline hyphomycetes, and 
mucormycetes; and aerobic actinomycetes.
    ++ Section 493.917(a)(3): For parasitology, we proposed that the 
annual program content must include intestinal parasites and blood and 
tissue parasites, if appropriate for the sample sources.
    ++ Section 493.919(a)(3): For virology, we proposed that the annual 
program content must include respiratory viruses, herpes viruses, 
enterovirus, and intestinal viruses, if appropriate for the sample 
sources.
    We summarize and respond to the public comments we received on 
these proposals and summarize our final policies in section III.E. of 
this final rule.
3. Declaration of Patient Reporting Practices
    The PT requirements at Sec.  493.801(b) specify that laboratories 
must examine or test, as applicable, the proficiency testing samples it 
receives from the proficiency testing program in the same manner as it 
tests patient specimens. CLIAC considered this requirement as applied 
to microbiology and agreed that PT programs should instruct 
laboratories to perform all testing as they normally would on patient 
specimens, including reporting PT results for microorganism 
identification to the same level reported on patient specimens. CLIAC 
deliberated on this issue and made the following recommendation:
     Laboratories should declare their patient reporting 
practices for organisms included in each PT challenge. However, PT 
programs should only gather this information as the inspecting agency 
is responsible for reviewing and taking action if necessary.
    We believe that laboratories should be instructed to report PT 
results for microbiology organism identification to the ``highest'' 
level that they report results on patient specimens to ensure that they 
do so to the ``same'' level that they report results on patient 
specimens. As a result, we proposed to amend Sec. Sec.  493.801(b), 
493.911(b), 493.913(b), 493.915(b), 493.917(b), and 493.919(b), to 
state that laboratories must report PT results for microbiology 
organism identification to the highest level that they report results 
on patient specimens. If finalized, this proposal should address an 
issue we identified during the PT program reapproval process in which 
we found laboratories inappropriately deciding whether to participate 
in a PT event based on the reporting criteria required by the PT 
program. We believe that this change will enhance consistency among the 
PT programs when grading samples.
    We summarize and respond to the public comments we received on 
these proposals and summarize our final policies in sections III.C. and 
III.E. of this final rule.
4. Gram Stain PT
    CLIAC considered whether the required PT for Gram stains should 
include both stain reaction and morphology. CLIAC concluded it should 
and recommended:
     PT results for Gram stains should include both stain 
reaction and morphology.
    We agree with this recommendation because knowing the bacterial 
morphology is essential for accurate identification of specific groups 
of bacteria. Therefore, we proposed the following in Sec.  493.911:
    ++ Section 493.911(a): The addition of required morphology for Gram 
stains.
    ++ Section 493.911(b): The evaluation of a laboratory's performance 
would be modified to include bacterial morphology as one part of the 
performance criterion for scoring the Gram stain.
    We summarize and respond to the public comments on these proposals

[[Page 41197]]

and summarize our final policies in section III.E. of this final rule.
5. Mixed Culture Requirement
    The current CLIA requirements for bacteriology Sec. Sec.  
493.911(b)(1), mycobacteriology 493.913(b)(1), and mycology 
493.915(b)(1) specify that at least 50 percent of the PT samples in an 
annual program must be mixtures of the principal organism and 
appropriate normal flora. This requirement aims to simulate the 
findings that would occur with actual patient specimens. In 
bacteriology, this 50 percent mixed culture requirement must be met for 
two required sample types, those that require laboratories to report 
only organisms that the testing laboratory considers to be a principal 
pathogen that is clearly responsible for a described illness (excluding 
immunocompromised patients) and those that require laboratories to 
report all organisms present. The CLIA requirements for 
mycobacteriology and mycology PT do not specify two sample types. 
Still, they include the 50 percent requirement for cultures containing 
a mixture of the principal organism and appropriate normal flora. None 
of the 50 percent mixed culture requirements in these subspecialties 
applies to samples that would only contain normal flora and no 
reportable organisms.
    CLIAC considered whether PT should include mixed cultures and 
discussed the difficulties of having mixed cultures in challenges for 
antimicrobial susceptibility testing. CLIAC considered lowering the 
mixed culture requirement to 25 percent for all subspecialties in 
microbiology. Upon deliberation, CLIAC made the following 
recommendation:
     Lower the mixed culture requirement from 50 percent to 25 
percent for PT challenges of both sample types (those that require 
laboratories to report only the principal pathogen and those that 
require laboratories to report all organisms present).
    We agree it is appropriate to lower the mixed culture requirement 
from 50 percent to 25 percent for bacteriology, mycobacteriology, and 
mycology to better reflect actual patient samples. As a result, we 
proposed the following changes:
    ++ Section 493.911(a)(2): In bacteriology, we proposed to decrease 
the required mixed cultures from 50 percent to 25 percent for culture 
challenges that require laboratories to report only the principal 
pathogen and those that require laboratories to report all organisms 
present.
    ++ Sections 493.913(a)(2) and 493.915(a)(2): In mycobacteriology 
and mycology, respectively, we proposed to decrease the mixed culture 
requirement from 50 percent to 25 percent.
    Since the requirements for parasitology and virology do not 
currently include requirements for mixed cultures (or mixed PT 
challenges), we did not propose to make any changes to these 
subspecialties. We summarize and respond to the public comments we 
received on these proposals and summarize our final policies in section 
III.E. of this final rule.
6. Antimicrobial Susceptibility Testing
    PT for antimicrobial susceptibility testing is currently required 
for bacteriology at Sec.  493.911(b)(1) and mycobacteriology at Sec.  
493.913(b)(1), but it is not required for mycology, parasitology, or 
virology. For antimicrobial susceptibility testing in bacteriology at 
Sec.  493.911(b)(3), at least one sample per testing event must include 
one Gram-positive or Gram-negative sample, and for mycobacteriology at 
Sec.  493.913(b)(3), at least one sample per testing event must include 
a strain of Mycobacterium tuberculosis with a predetermined pattern of 
susceptibility or resistance to the common antimycobacterial agents. In 
some instances, laboratories appreciate the opportunity to participate 
in additional susceptibility testing challenges as educational tools. 
Under the current regulations, some laboratories may perform the 
minimum required susceptibility testing on some organisms, such as 
Gram-positive cocci. When CLIAC discussed this issue, the point was 
made that by increasing the frequency and number of required 
susceptibility testing PT challenges for different groups of organisms, 
potential issues with patient testing in a laboratory may be detected 
sooner. CLIAC considered recommending increasing the susceptibility 
testing challenges to two per event and requiring one Gram-positive and 
one Gram-negative organism in each bacteriology testing event. CLIAC 
also considered whether PT should be required for resistance as well as 
susceptibility testing and whether these requirements should be 
extended to other microbiology subspecialties. Following this 
deliberation, CLIAC made the following recommendations:
     Required PT for antimicrobial susceptibility and/or 
resistance testing should be increased to two challenges per event for 
a total of six challenges per year in bacteriology and should include 
one Gram-positive and one Gram-negative organism in each event.
     PT should be required for laboratories that perform 
susceptibility and/or resistance testing in all microbiology 
subspecialties. It should include two challenges per event and should 
include resistant organisms.
    In considering these recommendations, we reviewed the modules 
currently offered by PT programs that include susceptibility testing 
and noted that there is a limited number of applicable PT modules 
currently available for resistance testing. Also, no PT program 
currently offers applicable PT modules for antiparasitic susceptibility 
or resistance testing in the subspecialty of parasitology. We believe 
it could be beneficial to increase the number of challenges per event 
from one to two for each microbiology subspecialty to increase the 
likelihood of detecting a problem in a laboratory. Antiparasitic 
susceptibility or resistance testing is not included in the 
subspecialty of parasitology because no PT program currently offers 
applicable PT modules. Therefore, we proposed the following:
    ++ Section 493.911(a)(4): For bacteriology, we proposed requiring 
at least two PT samples per event for susceptibility or resistance 
testing, including one Gram-positive and one Gram-negative organism 
with a predetermined pattern of susceptibility or resistance to common 
antimicrobial agents.
    ++ Section 493.913(a)(5): For mycobacteriology, we proposed 
requiring at least two PT samples per event for susceptibility or 
resistance testing, including mycobacteria that have a predetermined 
pattern of susceptibility or resistance to common antimycobacterial 
agents.
    ++ Section 493.915(a)(4): For mycology, we proposed requiring at 
least two PT samples per event for susceptibility or resistance 
testing, including fungi that have a predetermined pattern of 
susceptibility or resistance to common antifungal agents.
    ++ Section 493.919(a)(4): For virology, we proposed requiring at 
least two PT samples per event for susceptibility or resistance 
testing, including viruses that have a predetermined pattern of 
susceptibility or resistance to common antiviral agents.
    In each of these subspecialties, we also proposed to revise the 
requirements for the evaluation of a laboratory's performance at 
Sec. Sec.  493.911(b), 493.913(b), 493.915(b), and 493.919(b) to 
account for the fact that PT would be required for susceptibility or 
resistance

[[Page 41198]]

testing and that the scoring should be consistent with the testing 
performed.
    We summarize and respond to the public comments we received on 
these proposals and summarize our final policies in section III.E. of 
this final rule.
7. Direct Antigen Testing
    PT for direct antigen testing is only required for bacteriology and 
virology under Sec. Sec.  493.911(a) and 493.919(a), respectively, not 
for the other microbiology subspecialties of mycobacteriology, 
mycology, and parasitology. Since this type of testing is commonly used 
for testing patient specimens, especially in mycology and parasitology, 
CLIAC considered whether PT for direct antigen testing should be part 
of all of the microbiology subspecialty requirements. CLIAC indicated 
that direct antigen PT should be required in subspecialties where these 
methods are used, and PT is available and made the following 
recommendation:
     PT for direct antigen testing should be required for all 
microbiology subspecialties.
    We reviewed the modules currently offered by PT programs and 
determined that several modules include direct antigen testing for all 
microbiology subspecialties except mycobacteriology, for which this 
technology is not commonly used for testing patient specimens. In 
addition, we recognized that in bacteriology, PT for direct antigen 
testing to detect toxins produced by organisms such as Clostridioides 
(formerly Clostridium) difficile is also commonly available. Based on 
the information collected from the PT programs, availability of the 
modules, and importance to the health and safety of the public, we 
proposed to:
    ++ Retain the requirement for direct antigen detection for:

--Section 493.911(a)(1)(ii): Bacteriology.
--Section 493.919(a)(1)(i): Virology.

    ++ Add the requirement for direct antigen testing detection for:

--Section 493.915(a)(1)(i): Mycology.
--Section 493.917(a)(1)(i): Parasitology.

    ++ Require PT for bacterial toxin detection under Sec.  
493.911(a)(1)(iii). No changes were proposed for mycobacteriology.
    ++ Add the evaluation criteria of a laboratory's performance for 
two of the affected subspecialties under Sec. Sec.  493.911(b) and 
493.917(b) to include performance and scoring criteria that address 
direct antigen and toxin detection. Evaluation of a laboratory's 
performance for direct antigen testing at Sec.  493.917(b) would align 
with the other microbiology subspecialties and reflect current 
microbiology practices in reporting patient results. Evaluation of a 
laboratory's performance for bacterial toxin detection at Sec.  
493.911(b) would reflect the current practice of reporting patient test 
results (that is, absence or presence of bacterial toxin).
    We summarize and respond to the public comments we received on 
these proposals and summarize our final policies in section III.E. of 
this final rule.

B. Proposed Changes to PT for Non-Microbiology Specialties and 
Subspecialties

    In addition to determining which analytes should be added or 
deleted, CMS and CDC proposed to establish or change, if necessary, the 
criteria for acceptable performance, which include the target value and 
ALs, for the analytes. Currently, the CLIA regulations at Sec. Sec.  
493.927(c)(2), 493.931(c)(2), 493.933(c)(2), 493.937(c)(2), and 
493.941(c)(2) prescribe a variety of ALs, including: a multiple of the 
standard deviation (SD) of results from the mean of all laboratories in 
the peer group; fixed limit as a percentage of the assigned value; 
fixed limit in concentration units; and a mixture of percentage and 
concentration units, depending on the concentration of the analyte. As 
discussed in section II.B. of the proposed rule, for all new and 
currently required non-microbiology analytes, we proposed to amend 
certain analytes in Sec. Sec.  493.927, 493.931, 493.933, 493.937, and 
493.941 to include percentages with or without fixed ALs. Additionally, 
we proposed to tighten ALs for certain current analytes in Sec. Sec.  
493.927, 493.931, 493.933, 493.937, 493.941, and 493.959.
    We summarize and respond to the public comments we received on 
these proposals and summarize our final policies in section III.F. of 
this final rule.
1. Analytes Proposed for Addition to Subpart I
    The CLIA statute requires the PT standards established by the 
Secretary to require PT for each examination and procedure for which 
the laboratory is certified ``except for examinations and procedures 
for which the Secretary has determined that a proficiency test cannot 
reasonably be developed'' (42 U.S.C. 263a(f)(3)(A)). In determining 
whether PT can reasonably be developed for a given analyte, we 
considered whether the estimated cost of PT is reasonable in comparison 
to the expected benefit. We attempted to maximize improvements to the 
effectiveness of PT to improve accuracy, reliability and timeliness of 
testing while minimizing costs to the laboratories. In addition, we 
recognize that requiring PT for every analyte to derive benefits 
generalizable to all test methods is unnecessary. For example, 
systematic analytical problems on a multichannel analyzer might be 
detected by participation in PT for any of the analytes tested. 
Further, laboratories are already required under Sec.  493.1236(c)(1) 
to verify the accuracy of any test or procedure they perform that is 
not included in subpart I at least twice annually. Also, based on the 
results of the national PT survey conducted by CDC and the Association 
of Public Health Laboratories (APHL) in 2013, many laboratories 
voluntarily purchased PT materials for many nonrequired analytes. 
Keeping this in mind, as discussed in section II.B.2. of the proposed 
rule, we proposed adding the most crucial analytes based upon the 
following criteria:
    (1) Current availability of PT materials and the number of PT 
programs offering PT.
    (2) Volume of patient testing performed nationwide.
    (3) Impact on patient health and/or public health.
    (4) Cost and feasibility of implementation.
2. Process for Ranking Analytes Proposed for Addition to Subpart I
    We used a sequential process to narrow the list of eligible 
analytes for addition based on each of the four criteria listed above.
a. Current Availability of PT Materials and the Number of PT Programs 
Already Offering PT
    We believe that the availability of these PT samples for a 
particular analyte is an appropriate criterion for narrowing the list 
of eligible analytes and that scaling up a program would be relatively 
less difficult than creating a PT sample for a particular analyte that 
had not previously been offered. For the reasons noted below, we 
believe that at least three PT programs offering PT samples for a 
particular analyte under consideration would provide a sufficient 
number of programs to offer immediate access to PT by laboratories and 
a reasonable starting point for the analytes under consideration. CMS 
and CDC want to ensure that the laboratories could choose the best PT 
program for the services that their laboratories offered as well as not 
create a market advantage for a small number of PT programs. To 
evaluate the current availability of PT materials and PT

[[Page 41199]]

programs offering PT samples for a particular analyte, we analyzed the 
distribution of available PT programs for analytes for which PT is 
currently not required by subpart I of the CLIA regulations. The 
supporting data were collected from available sources, including data 
from PT program catalogs and data routinely reported by PT programs, 
including enrollment data. We examined the number of PT programs 
offering these analytes at any number of events per year and any number 
of challenges per event. We initially determined the number of analytes 
under consideration for which PT was offered by at least two, three, or 
four of the 11 existing PT programs. We determined that limiting the 
analytes under consideration to those for which PT was offered by at 
least three PT programs allowed a sufficient number of programs to 
offer immediate access to PT by laboratories and provided a reasonable 
starting point of 199 for the number of analytes under consideration 
(96 in routine chemistry, 27 in endocrinology, 28 in toxicology, 25 in 
general immunology, 21 in hematology, two for antibody identification). 
The expected impact on laboratories and PT programs was also considered 
(for example, minimizing the cost of purchasing and providing samples) 
when determining the minimum number of PT programs. Decreasing the 
minimum PT programs to two rather than three would increase the number 
of analytes under consideration to 303 but presumably decrease PT 
program availability and access for a given analyte. Conversely, 
increasing the minimum number of PT programs to four while presumably 
increasing PT program availability and access for a given analyte 
decreased the number of analytes under consideration to 164. This was 
the first cut based upon available PT modules.
b. Volume of Patient Testing Being Performed Nationwide
    For the second cut, we prioritized the remaining 199 analytes under 
consideration based upon estimated national testing volumes. We decided 
that an estimated national test volume of 500,000 per analyte annually 
was an appropriate threshold as it was based upon testing volumes of 
the majority (68 out of 81) of analytes currently listed in subpart I. 
For comparison, of the analytes currently required under subpart I, 63 
had a total national test volume above 1,000,000; five had national 
test volumes between 500,000 and 1,000,000, and 13 had national test 
volumes below 500,000. We used 500,000 annual tests as a preliminary 
cut-off for retention on the list of analytes under consideration. We 
also retained analytes below the 500,000 threshold that we determined 
to be clinically important based on literature already footnoted in 
section II.B.2.b. of the proposed rule and consultation with CDC health 
experts. The following analytes with test volumes less than 500,000 
that were retained are: carbamazepine, alpha-1-antitrypsin, 
phenobarbital, hepatitis Be antigen, antibody identification, 
theophylline, gentamicin, and tobramycin.
    In estimating national testing volumes to rank the remaining 199 
analytes under consideration in the proposed rule, we were unable to 
identify a single source of available data for all patient testing 
being performed nationwide. We had complete data for Medicare payment, 
as well as the most current MarketScan Commercial Claims and Encounters 
(CCAE) and MarketScan Medicaid Multi-state data sets \2\ and 
extrapolated accordingly. We used data provided by an HHS-approved 
accreditation organization, specifically a list of the number of their 
accredited laboratories offering each test we considered for addition 
to, or deletion from, subpart I to determine how many laboratories were 
performing testing for the proposed analytes. We also considered 
smaller representative data sets, including data sets obtained from a 
large healthcare network, a large reference laboratory, and a 
university hospital network, to evaluate the testing trends for the 
proposed analytes. We analyzed national testing trends based upon 
Medicare Part B payment data \3\ to determine the analytes in each 
specialty that are increasingly used for patient diagnosis and/or 
management. We concluded that the trends revealed in the data could 
continue to show increases in payment for the proposed analytes.
---------------------------------------------------------------------------

    \2\ 2009 Truven Health MarketScan[supreg] data, https://truvenhealth.com/your-healthcare-focus/life-sciences/data_databases_and_online_toolsMarkets/Life-Sciences/Products/Data-Tools/MarketScan-Databases.
    \3\ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4698806/.
---------------------------------------------------------------------------

    We estimated the 2009 national test volumes based upon two data 
sets: (1) Medicare Part B payment statistics (excluding waived 
testing); and (2) CCAE. For all analytes under consideration for the 
addition to subpart I, we used Current Procedural Terminology (CPT) 
codes from claims data. We identified all possible occurrences of a 
particular analyte and combined them into one count. For example, if 
bicarbonate could be performed in a panel and by itself, we included 
all possible occurrences.
    A complete count was available for the Medicare Part B data, and no 
estimation of total counts was necessary for this sector. MarketScan 
data, a sample of approximately 40 million covered individuals, was 
necessary to estimate CCAE data and approximately 6.5 million covered 
individuals for Medicaid data. Therefore, we estimated the total number 
of tests in both categories for the entire United States. The Agency 
for Healthcare Research and Quality (AHRQ) data showed that an 
estimated total of 181.5 million covered individuals enrolled in CCAE 
healthcare insurance; from this we derived a factor of 4.5 (181.5 
million individuals/40 million individuals) by which to multiply the 
MarketScan CCAE estimates to extrapolate estimates for the entire 
United States. Similarly, for the Medicaid estimates, we knew from CMS 
data that there were approximately 52.5 million individuals covered by 
Medicaid, so we derived a factor of 8.0 (52.5 million individuals/6.5 
million individuals) by which to multiply the MarketScan Medicaid 
estimates to extrapolate estimates for the entire United States.
    We note that these estimates did not account for some inpatient 
testing that was paid through capitation arrangements for inpatient 
testing. Testing paid directly by patients was also not counted 
because, in these cases, CPT codes would not be captured in the data 
because there was no request for reimbursement. Even with this 
limitation, we believe that these estimates provide a relative sense of 
the number of tests being performed annually per analyte. No other 
accurate data were available to us.
    As noted previously in this section, for the second cut, based upon 
our estimates of national testing volumes, we decided that an estimated 
national test volume of 500,000 per analyte annually was an appropriate 
threshold as most of the analytes listed in subpart I had national 
testing volumes above this threshold. Together with the above-described 
analytes below the 500,000 threshold that we determined to be 
clinically important, this narrowed our list of potential analytes 
under consideration for addition to subpart I to 73, representing 
analytes in five specialties or subspecialties
c. Impact on Patient and/or Public Health
    For the third cut, we considered the evidence available related to 
each analyte under consideration to assess patient and public health 
impact of

[[Page 41200]]

testing. Because there was no standardized, generally accepted way to 
assess this impact on clinical care and public health, we used the 
following to get a relative sense of the importance of the analytes 
under consideration: a review of published laboratory practice 
guidelines (LPGs); a review of critical values; and a review of the 
analyte's classification by the Food and Drug Administration (FDA).\4\ 
We accessed several data sources, including tests listed in the CDC 
Guide to Community Preventive Services; \5\ National Healthcare 
Priorities/Disparities reports; \6\ clinical practice guidelines 
including the National Guideline Clearinghouse (NGC) database available 
from AHRQ (https://www.guideline.gov/); critical values available in 
publications; and (CAP) Q-Probes.
---------------------------------------------------------------------------

    \4\ http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfClia/Search.cfm.
    \5\ https://www.thecommunityguide.org.
    \6\ https://www.ahrq.gov/research/findings/nhqrdr/index.html.
---------------------------------------------------------------------------

    In reviewing published LPGs, we hypothesized that if there were a 
relatively large number of LPGs available for a particular analyte, 
that analyte would be important for health testing. To estimate the 
number of LPGs, we used the AHRQ's NGC database. For example, there 
were 60 LPGs listed in the NGC for LDL cholesterol, 31 for hemoglobin 
A1c, and 27 for troponin, all of which are proposed for addition in 
Table 1. However, this approach did not differentiate analytes for 
which there were conflicting recommendations. For example, there are 
controversies about the value of screening men with prostate specific 
antigen (PSA) testing, and there is an ongoing debate about the 
prudence of testing vitamin D in asymptomatic adults (Kopes-Kerr, 
2013).
    To review critical values, which are pre-determined limits for 
specific analytes that, when exceeded, may suggest that immediate 
clinical intervention is required, we assessed analytes included in 
published on ``critical values'' lists. This approach allowed us to 
gauge the importance of an accurate result because an incorrect result 
could lead to a life-threatening intervention or a failure to 
intervene. We reviewed published literature and critical values posted 
online from 16 institutions, including small hospitals, university 
hospitals, and reference laboratories.
    As mentioned earlier in this proposed rule, we also assessed the 
clinical impact of an analyte by reviewing its medical device 
classification (Class I, II, or III) as categorized by the Food and 
Drug Administration's risk classification list. Similarly, we assessed 
the public health importance of the eligible analytes by counting the 
number of recommendations for testing the analytes from CDC's Morbidity 
and Mortality Weekly Report, the Infectious Disease Society of America, 
and the Council of State and Territorial Epidemiologists for 
surveillance of health conditions related to the particular analyte 
under consideration. We found supporting evidence for national 
prioritization in some of the following: the U.S. Preventive Services 
Task Force,\7\ the National Healthcare Quality and Disparities 
Report,\8\ and the CDC Hormone Standardization Program.\9\ For some 
analytes that are important to measure towards addressing health 
disparities and have public health impact, such as blood lead, we 
consulted with subject matter experts in CDC's National Center for 
Environmental Health, which promotes national testing and/or has 
standardization programs for some priority analytes, specifically 
estradiol and testosterone. CMS and CDC used this information to help 
determine which analytes should be included in the proposed rule.
---------------------------------------------------------------------------

    \7\ https://www.uspreventiveservicestaskforce.org/Page/Name/recommendations.
    \8\ https://www.ahrq.gov/research/findings/nhqrdr/index.html.
    \9\ https://www.cdc.gov/labstandards/hs.html.
---------------------------------------------------------------------------

    After assessing patient and public health impact on a case-by-case 
basis for the third cut, we narrowed the analytes down to 34 for 
consideration of addition to the proposed list of analytes in subpart 
I.
d. Cost and Feasibility of Implementation
    For the final analysis to determine whether an analyte would be 
proposed for inclusion in subpart I of the CLIA regulations, we focused 
on feasibility and costs of conducting PT for each of the remaining 34 
analytes under consideration. We provided each of the HHS-approved PT 
programs the opportunity to submit comments in writing related to: 
inclusion/deletion of analytes, grading schemes, method(s) for 
determining target values, evaluating data using peer groups, cost of 
including new analytes, and structure of microbiology PT. Analytes for 
which it would be difficult for the PT programs to scale up production 
to meet the CLIA required frequency of three events per year with five 
challenges per event were eliminated from consideration because we 
believe that the costs passed down to laboratories to purchase the PT 
would be overly burdensome. In other cases, the decisions were based on 
the difficulty of finding any suitable PT materials. Some potential 
analytes were eliminated because they were too unstable for product 
development or shipping or because the testing methodology was not 
sufficiently standardized to support PT, such as vitamin D testing. 
After assessing the cost and feasibility of implementing PT on a case-
by-case basis, we made the final cut, narrowing the analytes down to 29 
potential analytes for the proposed list of analytes in subpart I.
3. Specific Analytes Proposed for Addition to Subpart I
    Based upon the sequential process described previously in this 
final rule, information received from the PT programs, and consultation 
between CDC and CMS, we narrowed the list down to 29 analytes that we 
are proposing to add to subpart I of the CLIA regulations (Table 1).
BILLING CODE 4120-01-P

[[Page 41201]]

[GRAPHIC] [TIFF OMITTED] TR11JY22.000

BILLING CODE 4120-01-C
4. Analytes Proposed for Removal From Subpart I
    Recognizing that changes in the practice of clinical medicine have 
resulted in less frequent use of certain analytes, we used the same 
process to review the existing list of analytes in subpart I to 
determine which should be retained. In addition to requesting CLIAC's 
recommendations, we generally used the same criteria for retention of 
an analyte in subpart I as those used for determining which PT analytes 
to propose adding; however, as such PT testing was already available on 
the market, we did not consider the availability of PT material or the 
feasibility of implementation; therefore, we believe that PT programs 
already have the mechanism(s) in place to manufacture and ship PT for 
these analytes.
5. Process for Ranking and Assessing Existing Analytes and Proposals 
for Removal From Subpart I
a. Estimating Nationwide Testing Volume
    We generally used the same rationale to select currently required 
analytes to propose for deletion. Specifically, we used the same 
threshold of 500,000 tests performed annually as an initial criterion 
for considering PT analytes. Those estimated to be lower than this 
threshold were considered for deletion from required PT. In particular, 
we focused on PT for several therapeutic drugs (ethosuximide, 
quinidine, primidone, and procainamide and its metabolite, N-acetyl 
procainamide). New drugs that are more effective or safer have entered 
the market since 1992 and may have replaced the use of therapeutic 
drugs that were included in the 1992 regulations. If so, we would 
expect to see a continued decline in the volume of testing for the use 
of such drugs. In addition to identifying decreases in testing for 
these drugs, we looked for probable causes of those decreases. These 
decreases in testing could result from new and emerging tests, 
including methodologies, replacing older tests, new technology, and 
changes to the way that the medical community orders laboratory 
testing. For example, the decrease in testing for LDH isoenzymes could 
be explained by the increased reliance on better alternative cardiac 
markers, especially troponin. For some anticonvulsant drugs, there may 
have been changes in medical practice, including alternative drugs and 
other treatments, possibly decreasing the need to measure them. We 
identified 13 currently required analytes with national test volumes 
less than our 500,000 annual test volume threshold.
b. Estimated Impact on Patient and Public Health
    For any analyte still under consideration for removal, we performed 
literature reviews to determine if testing for alternative analytes or 
other diagnostic strategies had begun to supplant testing for the 
considered analyte. We took into account testing trends over the past 
10 years and we attempted to project

[[Page 41202]]

expected testing trends. We then assessed the critical importance of 
candidates for deletion from subpart I based upon the number of 
guidelines available in the AHRQ NGC and the same sources used for 
considering inclusion in subpart I, bearing in mind that for all 
analytes and tests that are not listed in subpart I, laboratories must 
demonstrate accuracy twice per year as specified at Sec.  
493.1236(c)(1). We also considered the potential impact of deleting 
these analytes on clinical medicine and public health. Based on our 
literature review and consultation with CDC health experts, we decided 
not to propose the elimination of eight analytes based upon their 
critical importance for patient testing: carbamazepine, alpha-1-
antitrypsin, phenobarbital, hepatitis B e antigen (HBeAg), antibody 
identification, theophylline, gentamicin and tobramycin. These are used 
for making important health decisions, for example, diagnosing 
hepatitis B (HBeAg), performing crossmatching for blood transfusions 
(antibody identification), or assessing compliance with medication for 
critically ill asthmatic patients (theophylline).
6. Analytes Proposed for Deletion From Subpart I
    Based upon the sequential process described previously in this 
final rule, we proposed that the following analytes be deleted from 
subpart I: at Sec.  493.931 LDH isoenzymes and at Sec.  493.937 
ethosuximide, quinidine, primidone, and procainamide (and its 
metabolite, N-acetyl procainamide).
7. Determining Criteria for Acceptable Performance
    ``Criteria for Acceptable Performance'', as that term is used in 
Sec. Sec.  493.923, 493.927, 493.931, 493.933, 493.937, 493.941, and 
493.959, is defined by the target value and acceptance limits. Criteria 
for acceptable performance is meant for PT scoring only and not 
intended to be used to set acceptability criteria for a laboratory's 
verification or establishment of performance specifications.
8. Setting Target Values
    Under Sec.  493.2, ``target value'' for quantitative tests is 
currently generally defined as either the mean of all participant 
responses after removal of outliers (those responses greater than 3 
standard deviations from the original mean) or the mean established by 
definitive or reference methods acceptable for use in the National 
Reference System for the Clinical Laboratory (NRSCL) by the National 
Committee for the Clinical Laboratory Standards (NCCLS). However, in 
instances where definitive or reference methods are not available or a 
specific method's results demonstrate bias that is not observed with 
actual patient specimens, as determined by a defensible scientific 
protocol, a comparative method or a method group (``peer'' group) may 
be used. If the method group is less than 10 participants, ``target 
value'' means the overall mean after outlier removal (as defined above) 
unless acceptable scientific reasons indicate that such an evaluation 
is inappropriate.
    Based on input from PT programs, we recognize, that peer grouping 
is generally the way that target values are set for most analytes. 
Therefore, in the proposed rule, we proposed to continue allowing PT 
programs to use peer grouping to set the target values. In addition, we 
proposed removing the reference to the NRSCL and NCCLS, while retaining 
the other options for setting target values.
9. Changing Acceptance Limits
    Because there have been improvements in technology resulting in 
better sensitivity, specificity, and precision, routinely using peer 
grouping to set target values means that the AL that were originally 
specified in each specialty and subspecialty of the CLIA `88 
regulations in subpart I effectively allow for more tolerant acceptance 
criteria for most analytes than would occur if targets were set by a 
reference method or overall mean. Based on feedback from several HHS-
approved PT programs, we believe it would be appropriate to update the 
ALs to reflect advancements in technology and analytical accuracy since 
the PT regulations were implemented in 1992. While narrowing limits may 
increase miss rates per challenge, we do not expect a high unsuccessful 
rate based on the data simulations provided by the PT programs. We 
expect the rates of unsatisfactory events would be low based on the 
simulation data and that the rates of unsuccessful events (two 
consecutive or two out of three testing events being unsatisfactory) 
would be even lower; therefore, we believed it was reasonable to 
propose tighter limits given current analytic accuracy. We used all 
data available to us to minimize the negative consequences of the 
proposed changes (for example, too many unsuccessful performances) to 
acceptance limits, including simulations provided by PT programs.
10. Changes to Percentage Acceptance Limits (ALs)
a. Basis for Using Fixed Percentage PT ALs
    Currently, the CLIA regulations at Sec. Sec.  493.927(c)(2), 
493.931(c)(2), 493.933(c)(2), 493.937(c)(2), and 493.941(c)(2) 
prescribe a variety of ALs, including: a multiple of the SD of results 
from the mean of other participants in the peer group; fixed limit as a 
percentage of the assigned value; fixed limit in concentration units; 
and a mixture of percentage and concentration units, depending on the 
concentration of the analyte. For all new and currently required non-
microbiology analytes, we proposed to use fixed ALs, preferably as 
percentage limits rather than concentration units.
    There are 53 analytes (existing or proposed) for which we proposed 
a percentage-based AL, for which biological variability data were 
published. There were no biological variability data for several 
analytes (for example, therapeutic drugs). Where there were such data, 
we used AL to get as close to, or below, an accuracy goal for the test 
that was based on biological variability data. Then we simulated 
several percentage-based ALs to see if their results would have passed 
or failed at each simulation. We wanted to get miss rates (that is, 
percent of laboratories that did not meet the criteria for acceptable 
performance per PT challenge) of somewhere in the 1 to 2 percent range 
as was observed in the data provided by the PT programs for current 
ALs. Of the 53 analytes, 34 of the proposed ALs were tighter than or 
equal to biological variability limits. For 19 analytes, the limits we 
are proposing are looser (greater) than the limits required to meet 
accuracy based upon biological variability. For these 19 analytes, 
using ALs based on biological variability would be untenable because 
the current analytical accuracy for such testing would not be expected 
to meet such limits. White blood cell differential is the only 
remaining analyte that would have ALs in SD. In this case there were no 
biological variability data available.
    In general, fixed ALs, either in percentages or concentration 
units, are preferred to SDs for PT for several important reasons: they 
can be tied directly to objective goals for performance, such as goals 
for analytical accuracy and technical expectations; they are constant 
in all PT events and do not vary because of statistical randomness, 
masked outliers, or small sample size; they assure the same evaluation 
criteria are used by all PT programs and discourage opportunities

[[Page 41203]]

for participants to ``shop'' for PT programs with less stringent 
criteria for which it is easier to achieve acceptable performance; they 
do not unfairly result in tighter effective ALs for peer groups that 
use analyzers that have tighter analytical precision; they can combine 
a fixed percentage and a fixed absolute concentration to allow for more 
robust evaluation while also fairly evaluating low analyte 
concentrations; and they are commonly used worldwide in other PT and 
external quality assessment programs.
    Our analysis of existing PT and external quality assessment 
programs showed that ALs using two or three SDs have been used in PT in 
a wide variety of settings for several reasons, such as: limited 
experience with PT or matrix effects for a particular analyte; lack of 
consensus on criteria for acceptable performance; inertia with no 
compelling pressure for change; and analytical performance so poor that 
multiples of the overall SD are considered to be the only fair 
approach. We believe all of these reasons to some extent contributed to 
initial reliance on SD limits for certain analytes when CLIA `88 was 
implemented. We also note that while regulations promulgated under CLIA 
`67 used ALs of three SD for several analytes, regulations finalized 
under CLIA`88 replaced these with fixed limits and PT programs 
successfully made the transition. Therefore, we believe it is likely 
that the proposed changes from SD-based ALs to fixed ALs will not be 
problematic.
    Therefore, as discussed in section II.B. of the proposed rule, we 
proposed to amend certain analytes in Sec. Sec.  493.927, 493.931, 
493.933, 493.937, and 493.941 to include fixed ALs with or without 
percentages. Three analytes have only concentration-based ALs (that is, 
no percentage-based ALs): pH, potassium, and sodium.
b. Adding Fixed Concentration Units to Fixed Percentage Units
    A percentage-based criterion can be unnecessarily stringent at low 
concentrations--either because of technical feasibility or because 
medical needs at the low concentration do not require such tight 
precision. Thus, when percentage-based fixed criteria are used for ALs, 
it may be necessary to place a minimum on the percentage as currently 
occurs with the criterion for acceptable performance for glucose (Sec.  
493.931) for which the AL switches from 10 percent to 6 mg/dL below a 
concentration of 60 mg/dL. The combined ALs direct PT programs to score 
with whichever of the specifications is more tolerant; at lower limits 
of the analytical range this will be the fixed concentration limit. 
Therefore, to allow for fairer and more realistic ALs, we proposed to 
use combinations of percentage and concentration limits as appropriate. 
These combination limits are similar to limits that already exist in 
CLIA `88 regulations for glucose and other analytes.
    Therefore, we proposed to amend certain analytes in Sec. Sec.  
493.927, 493.931, 493.933, 493.937, 493.941, and 493.959 to include 
percentage-based ALs with or without additional fixed ALs.
c. Establishing ALs Based on Analytical Accuracy Goals for Proposed New 
and Several Current Analytes
    For the newly proposed analytes and several current analytes for 
which current ALs are in units other than percentages such as three SDs 
or concentration units, we proposed to change the ALs to percentages. 
Over the years, there have been many proposed criteria for establishing 
goals for analytical performance. The various possible approaches were 
reviewed and a hierarchy was established based on a 1999 consensus 
conference. These strategies were reconsidered at the 2014 European 
Federation of Clinical Chemistry and Laboratory Medicine Strategic 
Conference in Milan. Participants in both conferences acknowledged that 
the ability of a test method to meet clinical needs is the highest 
priority, and the most defensible approach would be clinical trials in 
which patient outcomes could be compared using different analytical 
accuracy goals. This approach was not feasible for many reasons. 
Although clinical outcomes studies would be the most rigorous basis for 
establishing analytical performance goals, these are seldom possible, 
leaving the natural dispersion of levels for each analyte (biological 
variability) as the next best scientifically defensible approach for 
establishing analytical accuracy goals. The less the biological 
variability, the more stringent the analytical accuracy needs to be. 
This approach makes sense for two of the most important reasons to 
conduct patient testing: diagnosis of disease, that is, differentiating 
an abnormal result from a normal one, and monitoring a patient's 
progress during treatment. In the former case, we believe that the 
``within-group'' biological variability is the important limiting 
factor defining an appropriate error goal for a test method. 
Furthermore, we believe the most important factor for monitoring 
progress is the ``within individual'' variability. It was not possible 
for us to differentiate how analytes are being used or will be used 
clinically, with respect to diagnosis versus monitoring. Therefore, we 
accounted for both needs and used an approach that accounted for both 
kinds of biological variability to estimate analytical accuracy goals 
as the basis for our proposals for acceptance limits in percentages. 
The advantage of using analytical accuracy goals that are expressed in 
terms of percentages is that they can be directly related to ALs in a 
mathematical way expressed as percentages.
    We have assumed that a laboratory that can meet the clinical needs 
for test accuracy based upon biological variability should perform 
successfully on PT most or all of the time. Therefore, whenever 
possible, we have used publicly available estimates of allowed total 
error based upon estimates of biological variability to approximate the 
proposed AL. CDC has shown in a recent poster \10\ that it is possible 
to design ALs based upon such accuracy goals, and it is possible to 
simulate the ability of a PT program to identify laboratories that 
cannot meet such goals, while minimizing the likelihood of 
misidentifying laboratories that are meeting analytical accuracy goals 
based upon biological variability.
---------------------------------------------------------------------------

    \10\ Astles, Tholen, and Mitchell, 2016, https://www.aacc.org/science-and-practice/annual-meeting-abstracts-archive.
---------------------------------------------------------------------------

    Therefore, we proposed to amend ALs for certain current analytes as 
well as establish ALs for analytes proposed for addition in Sec. Sec.  
493.927, 493.931, 493.933, 493.937, 493.941 and 493.959 based on 
analytical accuracy goals.
d. Tightening Existing Percentage ALs as Needed
    There have been significant improvements in laboratories' 
performance in PT for the great majority of analytes and PT 
unsatisfactory rates have dropped for all types of laboratories. The 
improvements are such that, for many analytes, laboratories that began 
to use PT to comply with CLIA `88 now perform as well as the hospital 
and independent laboratories that were previously required to perform 
PT under CLIA `67. Howerton, et al., showed that for almost all 
analytes examined, PT performance improved somewhat after CLIA `88 was 
implemented, but the improvements were greater for laboratories that 
were not previously required to perform PT. The rates of unsatisfactory 
PT are now roughly the same for analytes listed in subpart I, 
regardless of the laboratory type. This is consistent with CLIA's 
intent to ensure accurate clinical testing regardless of the setting 
where testing is performed. There are several factors

[[Page 41204]]

contributing to the improvements in PT performance, including improved 
analytical methods being used in all settings, technological advances 
resulting in improved precision, sensitivity and specificity, and 
increased familiarity with handling preparation, and reporting of PT 
samples. Therefore, for the reasons above as well as supporting 
simulation data date from the PT programs, we proposed to make criteria 
for acceptable performance for existing analytes listed in subpart I 
(Sec. Sec.  493.927, 493.931, 493.933, 493.937, 493.941 and 493.959) 
tighter, so they are in closer agreement with analytical accuracy goals 
which are based upon biological variability and simulation data.
e. Simulating the Impact of New ALs on Unacceptable Scores for 
Challenges and Unsatisfactory Rates for Events
    We evaluated a very specific PT data set to help set appropriate 
limits. The total simulations reproduced PT that covered 2 years, 
representing 30 challenges (three events per year; five challenges per 
event; 2 years) of each proposed new analyte and for the analytes for 
which we propose to modify ALs. We reviewed the aggregated percentage 
of unacceptable scores for each PT challenge using retrospective data. 
We then reviewed the simulation data which applied two or three new ALs 
for each of 84 analytes (consisting of 27 new analytes and 57 existing 
analytes). Based on the simulation data, we were able to make informed 
decisions to help us create or adjust the ALs.
    Based upon our analysis of the simulation results, we further 
refined the proposed ALs and added potential absolute concentrations in 
lieu of percentage ALs, as was described previously in this final rule. 
We then requested narrowly tailored data from PT programs as described 
previously in this final rule using retrospective PT data and peer 
group data for scoring, as they ordinarily would do. We focused on 
unsatisfactory scores with the data so that we could calculate the 
unsatisfactory rate per analyte among all participating laboratories 
that might occur with each proposed AL. The final simulations were 
conducted by several of the PT programs and this set of data was used 
to determine the proposed ALs.
    We compared the unacceptable scores for each challenge and each 
proposed AL to determine at which concentrations it would be necessary 
to switch to a fixed concentration AL. Using this approach, we were 
able to identify an AL for each analyte and, in some cases, an 
additional concentration-based AL. This approach enabled us to identify 
an AL that would be sensitive enough to identify poor-performing 
laboratories, yet not so sensitive that it will incorrectly identify 
laboratories that likely meet requirements for accuracy.
f. Limitation in Our Ability To Predict the Number of New 
Unsatisfactory and Unsuccessful Scores
    It is not possible for us to predict the precise effect of the 
proposed changes on the number of unsatisfactory and unsuccessful 
scores. The occurrence of an unsatisfactory score for a PT event 
depends upon at least two of five challenges being graded as 
unacceptable or outside the criteria for acceptable for performance. PT 
programs select different combinations of samples for each event and it 
is impossible to predict how their selection could be modeled 
statistically. Finally, the distribution of unsatisfactory and 
unsuccessful PT scores is not randomly distributed across all 
participants.
    ++ Sections 493.923(a), 493.927(a), 493.931(a), 493.933(a), 
493.937(a), 493.941(a), and 493.959(b): We proposed to amend these 
provisions to remove the option that PT samples, ``at HHS' option, may 
be provided to HHS or its designee for on-site testing''.
    ++ Section 493.927: We proposed to amend the criteria for 
acceptable PT performance to permit scoring of quantitative test 
results for the following immunology analytes: antinuclear antibody; 
antistreptolysin O; rheumatoid factor; and rubella. For these analytes, 
we have determined that there are one or more test systems that 
currently report results in quantitative units; therefore, we added ALs 
based on percentages or target values in addition to retaining the 
qualitative target values. We proposed to make this allowance in CLIA 
for reporting PT which reflects current practice.
    ++ Section 493.931(b): We proposed making a technical change to the 
description for creatine kinase isoenzymes to be CK-MB isoenzymes, 
which may be measured either by electrophoresis or by direct mass 
determination.
    ++ Section 493.933: We proposed adding the following analytes: 
estradiol, folate (serum), follicle stimulating hormone, luteinizing 
hormone, progesterone, prolactin, parathyroid hormone, testosterone, 
and vitamin B12.
    ++ Section 493.937(a): We proposed revising this provision by 
including the requirement that annual PT programs must provide samples 
that cover the full range of values that could occur in patient 
specimens. We proposed this amendment so that PT programs must provide 
samples across a toxicology sample's entire reportable range rather 
than just provide samples within a sample's therapeutic range.
    ++ Section 493.941: We differentiated the criteria for units of 
reporting of the analyte prothrombin time. We proposed to amend the 
criteria for acceptable performance to reflect both in seconds and/or 
INR (international normalized ratio) and to add the requirement that 
laboratories must report prothrombin time for PT the same way they 
report it for patient results. We also proposed to add criteria for 
acceptable performance for directly measured INR for prothrombin time. 
Additionally, we proposed to require laboratories performing both cell 
counts and differentials to conduct PT for both (that is, the ``or'' 
would be changed to an ``and''). Finally, we proposed changing the 
criteria for acceptable performance for ``cell identification'' from 90 
percent to 80 percent. We proposed this change as the requirement of 
five samples per event does not allow for a score of 90 percent (that 
is, five samples would allow for scores of zero percent, 20 percent, 40 
percent, 60 percent, 80 percent, or 100 percent). PT for cell 
identification is currently required in Sec.  493.941. Further, Sec.  
493.851(a) states that ``failure to attain a score of at least 80 
percent of acceptable responses for each analyte in each testing event 
is unsatisfactory performance for the testing event.'' If the 
requirement for acceptable performance remains at 90 percent, a 
laboratory can only have satisfactory performance if they receive 100 
percent; however, Sec.  493.851(a) allows satisfactory performance for 
both 80 percent and 100 percent.
    ++ Section 493.959: We proposed changing the criteria for 
acceptable performance for unexpected antibody detection from 80 
percent accuracy to 100 percent accuracy. We proposed this change 
because it is critical for laboratories to identify any unexpected 
antibody when crossmatching blood in order to protect public health and 
not impact patient care.
    ++ Sections 493.923(b)(1), 493.927(c)(1), 493.931(c)(1), 
493.933(c)(1), 493.937(c)(1), 493.941(c)(1), and 493.959(d)(1): We 
proposed amending these provisions to clarify that to achieve 
consensus, PT programs must attempt to grade using both participant and 
referee laboratories before determining that the sample is ungradable. 
We believe that this change will enhance consistency among the PT 
programs when grading samples. The current regulations noted previously

[[Page 41205]]

allow for scoring either with participants or with referees before 
calling a sample ungradable.

C. Additional Proposed Changes

    We proposed to amend Sec.  493.2 by modifying the definition of an 
existing term and defining new terms as follows:
     Target value: We proposed removing the reference to NRSCL 
and NCCLS and retaining the other options for setting target values in 
this final rule.
     Acceptance Limit: We proposed defining this term to mean 
the symmetrical tolerance (plus and minus) around the target value.
     Unacceptable score: We proposed defining this term to mean 
PT results that are outside the criteria for acceptable performance for 
a single challenge or sample.
     Peer group: We proposed defining this term as a group of 
laboratories whose testing process utilizes similar instruments, 
methodologies, and/or reagent systems and is not to be assigned using 
the reagent lot number. PT programs should assign peer groups based on 
their own policies and procedures and not based on direction from any 
manufacturer.
    We proposed the following revisions to the regulation text at 
subpart A:
     Sections 493.20 and 493.25: We proposed to amend the 
regulations to reflect that if moderate and high complexity 
laboratories also perform waived tests, compliance with Sec.  
493.801(a) and (b)(7) are not applicable. However, we proposed to 
continue to require compliance with Sec.  493.801(b)(1) through (6) to 
align the regulations with the CLIA statute (42 U.S.C. 263a (i)(4)), 
which does not exclude waived tests from the ban on improper PT 
referral.
    We proposed to revise the regulation text at subpart H:
     Section 493.861: We proposed amending the satisfactory 
performance criteria for failure to attain an overall testing event 
score for unexpected antibody detection from ``at least 80 percent'' to 
``100 percent.'' We proposed this change because it is critical for 
laboratories to identify any unexpected antibody when crossmatching 
blood to protect the public health and not impact patient care.
    We proposed to revise the regulation text at subpart I:
     Section 493.901(a): We proposed to require that each HHS-
approved PT program must have a minimum of 10 laboratory participants 
before offering any PT analyte. We recognize that PT programs do not 
grade results when there are fewer than 10 laboratory participants. 
This would require the laboratory to perform additional steps to verify 
the accuracy of their results. If at any time a PT program does not 
meet the minimum requirement of 10 participating laboratories during 
the reapproval process for an analyte or module, HHS may withdraw 
approval for that analyte, specialty, or subspecialty. This change 
reduces some burden on laboratories that have incurred the expense of 
enrolling in a PT program but do not receive a score or receive an 
artificial score requiring the laboratory to take additional steps to 
verify the accuracy of the analyte as required by Sec.  493.1236(b)(2).
     Section 493.901(c)(6): We proposed to add the requirement 
that PT programs limit the participants' online submission of PT data 
to one submission or that a method be provided to track changes made to 
electronically reported results. Many PT programs currently allow 
laboratories an option to report PT results electronically, while some 
other PT programs only allow laboratories to report PT results 
electronically with no other option such as facsimile or mailed PT 
submission forms. However, at this time, the PT programs that do 
participate in the online reporting have no mechanism to review an 
audit trail for the submitted result. In some cases of PT referral, it 
has been discovered that laboratories have sent PT samples to another 
CLIA-certified laboratory for testing, received results from the other 
laboratory, and then changed their online reported results to the PT 
program since those results can be modified up until the PT event close 
date. In an effort to assist in PT referral investigations and 
determinations, an audit trail that includes all instances of reported 
results would aid in determining if a laboratory compared PT results 
obtained from another laboratory and changed their previously submitted 
results.
     Section 493.901(c)(8): We proposed to add to the 
requirement previously found at Sec.  493.901 that contractors 
performing administrative responsibilities as described in Sec. Sec.  
493.901 and 493.903 must be a private nonprofit organization or a 
Federal or State agency or nonprofit entity acting as a designated 
agent for the Federal or State agency. Several PT programs have divided 
their administrative and technical responsibilities into separate 
entities or have had the administrative responsibilities performed by a 
contractor. We were made aware that administrative responsibilities 
were being performed by a for-profit entity. Because the CLIA statute 
(42 U.S.C. 263a(f)(3)(C)) requires PT programs to be administered by a 
private nonprofit organization or a State, we are proposing to amend 
Sec.  493.901 to state that all functions and activities related to 
administering the PT program must be performed by a private nonprofit 
organization or State.
     Section 493.901(e): We proposed the requirement that HHS 
may perform on-site visits for all initial PT program applications for 
HHS approval and periodically for previously HHS-approved PT programs 
either during the reapproval process or as necessary to review and 
verify the policies and procedures represented in its application and 
other information, including, but not limited to, review and 
examination of documents and interviews of staff.
     Section 493.901(f): We proposed an additional requirement 
to the regulation that specifies we may require a PT program to reapply 
for approval using the process for initial applications if widespread 
or systemic problems are encountered during the reapproval process. The 
initial application for the approval as an HHS PT program requires more 
documentation in the application process than that which is required of 
PT programs seeking HHS reapproval.
     Section 493.903(a)(3): It has come to our attention that 
PT programs may have on occasion modified a laboratory's PT result 
submission by adding information such as the testing methodology which 
was inadvertently omitted by the laboratory. Therefore, we proposed 
adding the requirement that PT programs must not change or add any 
information on the PT result submission for any reason, including, but 
not limited to, the testing methodology, results, data, or units.
     Section 493.905: We proposed adding that HHS may withdraw 
the approval of a PT program at any point in the calendar year if the 
PT program provides false or misleading information that is necessary 
to meet a requirement for program approval or if the PT program has 
failed to correct issues identified by HHS related to PT program 
requirements. We also proposed adding a requirement that the PT program 
may request reconsideration should we determine that false or 
misleading information was provided if the PT program has failed to 
correct issues identified by HHS related to PT program requirements.

III. Analysis of and Responses to Public Comments

    We received 107 public comments in response to the February 4, 
2019,

[[Page 41206]]

proposed rule. The commenters represented individuals, PT programs, 
accreditation organizations, laboratory professional organizations, and 
businesses, including in vitro diagnostics manufacturers. Commenters 
were generally supportive of the proposed changes, and some noted that 
these changes would increase flexibility and be a positive change for 
both laboratories and PT programs, especially in the specialty of 
microbiology. A few commenters recommended clarification of proposed 
changes or suggested specific changes, including alternative language, 
to the proposed requirements. After analyzing the comments received, we 
have modified or deleted several provisions in this final rule. A few 
commenters raised issues that are beyond the scope of our proposals. We 
are not summarizing or responding to those comments in this final rule. 
However, we reviewed the comments to consider whether to take other 
actions, such as revising or clarifying the CLIA program operating 
instructions or procedures, based on the information or recommendations 
in those comments. Our responses to specific comments are as follows:

A. Delayed Effective Date and Ongoing Process for Updating PT 
Regulations (Sec. Sec.  493.2 and 493.801 Through 493.959)

    Comment: Several commenters requested that there be a delayed 
effective date or phase in approach for implementation of the updated 
PT requirements to give all affected constituents time to accommodate 
the changes. Two commenters suggested that CMS develop an ongoing 
process to make changes to the PT regulations to ensure timely 
implementation of the updates.
    Response: We recognize that time will be needed for laboratories, 
PT programs, accreditation organizations, exempt States, and surveyors 
to adopt the updated PT requirements related to subparts H and I. As 
such we are delaying the effective date of the revisions to Sec. Sec.  
493.2 and 493.801 through 493.959 until 2 years after the publication 
of this final rule in the Federal Register. The delayed effective date 
reflects the timeframe that we believe PT programs will need to produce 
the PT samples to meet the revised regulations and incorporate any 
updates to PT reporting requirements. In addition, laboratories will 
need to implement the new PT requirements after the samples are 
available from the PT programs. We encourage laboratories to enroll in 
the new and revised analytes prior to the delayed effective date. We 
also appreciate the commenters' suggestions for a process to address 
needed PT changes more quickly on an ongoing basis. We will consider 
possible ways to streamline the process going forward in light of the 
required timeframe for rulemaking. We note that the regulations related 
to laboratories performing tests of moderate complexity and high 
complexity testing that also perform waived testing and proficiency 
testing enrollment, Sec. Sec.  493.20 and 493.25, respectively, will be 
effective 30 days after the publication date of this final rule.

B. Definitions (Sec.  493.2)

    Comment: A commenter stated that the term ``unacceptable score,'' 
as defined at Sec.  493.2, was confusing and should be replaced with 
``unacceptable result.'' Other commenters pointed out that the 
organization of sub-bullets under the definition of ``target value'' 
was incorrect as the content in (iv) does not belong under (1), but 
should be included as (2) under the definition.
    Response: We agree with commenters that the term ``unacceptable 
score'' could be confusing because it could be interpreted to mean a 
total analyte event score rather than the intended meaning of referring 
to a single challenge or sample result. Since this term is not included 
in the CLIA regulations except for the proposed amendments to Sec.  
493.2, we are not finalizing this term in Sec.  493.2 in this final 
rule. With respect to the proposed definition of ``target value'', we 
agree with the commenter about the paragraphs included under that 
definition and are making the recommended change in this final rule.
    Comment: While several commenters supported the inclusion of a 
definition for ``peer group'' in the proposed rule, other commenters 
expressed concerns about our proposal. Three commenters approved of our 
proposal to disallow peer-grouping to the reagent lot level, while two 
commenters did not agree with the proposal. One commenter noted that 
matrix effects, known to cause PT materials to behave differently from 
unmodified patient samples, are the reason underlying the need to use 
peer grouping to set target values and grade PT results. This commenter 
was concerned that the final rule would not account for the existence 
of matrix effects by not allowing peer grouping. One commenter 
suggested we consider conducting a scientific study to assess the 
contribution of calibration errors versus matrix effects in causing 
differences in PT results.
    Response: In response to the comments about peer-grouping to the 
reagent lot level, PT is one of the important ways to detect problems 
in FDA-cleared/approved test methods. Differences between reagent lots 
used during testing may occur due to the manufacturing process. 
Allowing peer grouping to the lot level may inhibit the detection of 
these problems. We are not prohibiting PT programs from interacting 
with manufacturers to discover problems with reagent lots. However, the 
PT program has the responsibility for interpreting correct PT results. 
If a PT program determines that a specific reagent lot failure 
occurred, it should inform the affected laboratories and manufacturer. 
Concerning the comment about matrix effects, currently CLIA requires PT 
programs to demonstrate through a scientific protocol that bias, such 
as matrix effects, existed in PT materials before allowing peer-
grouping to grade results. We are aware that PT programs have typically 
not used a scientific approach to determine if a peer group should be 
used as the process of demonstrating matrix effects is expensive and 
time-consuming. This rule finalizes the proposed definitions for both 
``peer group'' and ``target value'' and will continue to allow peer-
grouping for evaluation of PT results, without requiring prior 
demonstration of matrix effects. We do not expect there will be a 
change in how peer groups are identified by PT programs. Therefore, 
there will be no change in how target values are determined based upon 
the mean of peer group results. In response to the proposed study of 
commutability to demonstrate differences in PT results based on 
calibration errors, the comment is outside the scope of this final 
rule.
    Comment: Two commenters suggested that CLIA should not require 
removal of outliers using a three standard deviation (3 SD) criterion 
when grading PT, as required under the proposed definition of target 
value in Sec.  493.2. One commenter noted that the requirement to 
remove outliers was done to get a better estimate of the SD, which 
would only apply to one analyte after the final rule is effective. The 
other commenter stated that outlier removal using a 3 SD limit is not 
recommended according to ISO 13528:2015. Both commenters noted the need 
for robust methods to remove outliers, which can be especially 
problematic when the PT peer group is very small, such as a group that 
includes only 5 to 20 results.
    Response: It is important that outliers be removed to set target 
values. Because a spurious PT result, including one due to a 
transcription error, could affect the peer group mean, especially when 
the peer group has relatively few laboratory

[[Page 41207]]

participants, PT programs should continue to discard aberrant results 
when calculating the peer group target. At this time, we do not have 
sufficient information to provide additional or alternative options for 
outlier removal. However, we recognize the need for PT programs to have 
valid modern approaches for outlier removal. Therefore, we are 
retaining the requirement to remove outliers as described in the 
definition for target value, using a 3 SD criterion. Regarding the 
comment referencing ISO requirements, we note that ISO standards do not 
apply to CLIA.
Summary of Final Actions
     We did not receive any comments on the proposed definition 
of ``acceptance limit'' and are finalizing the definition with a 
clarifying technical edit.
     Based on the public comments received, we are finalizing 
the proposed definition of ``peer group'' with a clarifying technical 
edit.
     We are revising and finalizing the proposed definition for 
``target value.'' We have corrected the organization of the paragraphs 
and have moved the content of subparagraph (iv) to paragraph (2).
     We are not finalizing the proposed definition of 
``unacceptable score.''

C. Enrollment and Testing of Samples (Sec. Sec.  493.20(c) and 
493.25(d))

    Comment: A number of commenters expressed concerns or requested 
clarification about the proposal to amend Sec. Sec.  493.20(c) and 
493.25(d) to reflect that if laboratories certified to perform moderate 
and high complexity testing, respectively, also perform waived tests, 
compliance with Sec.  493.801(a), which requires enrollment in PT, and 
(b)(7), requiring PT for the primary method of patient testing, are not 
applicable for the waived tests. However, as proposed, if laboratories 
voluntarily enrolled in PT for their waived testing, Sec.  
493.801(b)(1) through (6) would apply in cases of improper PT referral 
for those tests. Commenters expressed that laboratories may be 
discouraged from voluntarily enrolling in PT for waived tests if the 
possibility of sanctions for referred PT existed. Two commenters 
recommended that PT should be required for all testing, including 
waived testing. One commenter requested clarification of whether 
laboratories would need to verify the accuracy of waived tests twice 
per year.
    Response: Subsection (d)(2)(C) of the CLIA statute states that 
subsections (f) and (g) shall not apply to a laboratory issued a 
Certificate of Waiver. Subsection (f) is related to issuing standards 
that, at a minimum, allow a laboratory to consistently perform testing 
to ensure accurate and reliable test results, including the requirement 
for all laboratories that perform nonwaived testing to enroll in an 
approved PT program and to verify the accuracy of tests twice per year. 
Subsection (g) speaks to inspecting laboratories for compliance with 
subsection (f) and are generally done on a biennial basis. However, 
sanctions related to PT referral are in subsection (i), which is not 
limited to nonwaived laboratories but rather allows sanctions to be 
taken against ``any laboratory'', including a Certificate of Waiver 
laboratory, that intentionally refers PT samples to another laboratory. 
Some Certificate of Waiver laboratories and other laboratories that 
perform waived testing have voluntarily chosen to enroll in PT for 
waived testing over the history of the CLIA program to ensure the 
quality of their testing. We have no reason to believe these 
laboratories will be discouraged from continuing their enrollment in 
PT. As a result, we are finalizing the new requirements at Sec. Sec.  
493.20(c) and 493.25(d) to ensure that the CLIA regulations align with 
the statute.
Summary of Final Actions
     We are finalizing the proposed revisions at Sec. Sec.  
493.20(c) and 493.25(d).
     We are finalizing the proposed revisions at Sec. Sec.  
493.801 and 493.861. Section 493.801 will require laboratories to 
report PT results for microbiology organism identification to the 
highest level that they report results on patient specimens. Section 
493.861 will amend the satisfactory performance criteria for failure to 
attain an overall testing event score for unexpected antibody detection 
from ``at least 80 percent'' to ``100 percent.'' We received no 
comments on the proposed revisions at Sec. Sec.  493.801 and 493.861.

D. PT Program Approval and Administration (Sec. Sec.  493.901, 493.903, 
493.905)

    Comment: Two commenters urged CMS not to change the current codes 
used for specific analytes when PT programs report PT results to CMS 
and to create new codes for the analytes being added.
    Response: We understand the commenters to be referring to certain 
analyte-specific codes that are used as an internal data system 
designation for PT programs to report PT analyte results to us. 
Although these codes are not explicitly referenced in the regulations, 
we agree with the commenters and note that the current analyte-specific 
codes for PT will remain the same. New analyte-specific codes will be 
generated for the newly required PT analytes.
    Comment: Many commenters remarked on the requirement proposed at 
Sec.  493.901(a) having at least 10 laboratory participants for an 
analyte before a program is approved to offer that analyte. Commenters 
stated that this requirement could inhibit development of new PT, and 
be detrimental to both laboratories and PT programs, especially smaller 
programs, which could find it harder to compete. Some commenters 
pointed out that PT programs offering newly required analytes would 
naturally have relatively fewer participating laboratories. One 
commenter requested clarification on whether this requirement would 
apply only to newly required analytes or to all PT analytes. Some 
commenters pointed out that PT programs may not initially know how many 
laboratories would enroll, and the programs would need time to develop 
their market. One commenter stated that this requirement would be a 
burden and result in more ungraded events.
    Response: The requirement for at least 10 laboratory participants 
would only apply for PT analytes required in subpart I, and therefore, 
should not impact the development of PT for new or emerging analytes to 
the extent that they are not listed in subpart I. We realize that PT 
programs seeking HHS approval for the first time may not know how many 
laboratories would enroll in their program, and we did not intend to 
require at least 10 laboratory participants when PT programs apply for 
initial approval. We intend to review the number of laboratory 
participants for each program and each HHS-approved analyte during the 
annual reapproval process. If a PT program has fewer than 10 
participants, we may not reapprove the PT program for a specific 
analyte. As a result of the comments, in this final rule, we are 
clarifying the requirement at Sec.  493.901(a) to state ``for each 
specialty, subspecialty, and analyte or test for which the proficiency 
testing program is seeking reapproval'' to better reflect the PT 
approval process.
    Comment: A number of commenters representing several PT programs 
and accreditation organizations commented on the requirement proposed 
at Sec.  493.901(c)(6) that for those results submitted electronically, 
a mechanism to track changes to any result reported to the proficiency 
testing program and the reason for the change. There was general 
opposition due to perceived burden and expense, both to PT

[[Page 41208]]

programs and laboratories, and possibilities for errors. Some 
commenters stated that they are currently unable to know when every PT 
result is entered or changed if done electronically based on the 
technology used for laboratories to submit results. There were also 
questions about the circumstances under which PT programs would be 
required to provide audit trails. One commenter agreed with this 
proposed change but recommended that we provide more guidance to 
laboratories on how to meet this requirement.
    Response: We appreciate the information provided by the commenters 
expressing the challenges with meeting this requirement. We do require 
laboratories to maintain documentation of their submissions to PT 
programs (see Sec.  493.801(b)(5)). However, based on the comments 
received, we are not finalizing the requirement proposed at Sec.  
493.901(c)(6).
    Comment: Several commenters expressed concerns about the 
requirement proposed at Sec.  493.901(c)(9) that a contractor 
performing administrative responsibilities as described in Sec. Sec.  
493.901 and 493.903 must be a private nonprofit organization or a 
Federal or State agency, or an entity acting as a designated agent for 
the Federal or State agency. A commenter noted that many essential PT 
program functions are currently performed by for-profit entities or 
subcontractors. There was a general consensus among commenters that 
many important administrative functions could not be performed without 
contractual arrangements with for-profit entities, such as 
transportation services.
    Response: We recognize that some functions required as part of the 
PT process, such as transportation services, are provided by for-profit 
entities. Other business functions may also be provided by for-profit 
contractors, such as obtaining and manufacturing the PT specimens/
products, initial testing to establish approximate target values as 
prescribed by the PT program, aliquoting and labeling samples, testing 
to assure homogeneity and stability of samples, long-term storage of 
samples for use in future PT events, and storage of aliquoted PT 
samples for additional testing as may be requested by the clients, or 
required by us. Also, ``for-profit'' entities can be used or contracted 
for distributing/mailing out the PT kits to the laboratories. This 
proposed requirement was not intended to address those aspects of PT 
program operations, but rather the technical and scientific 
responsibilities as described in Sec. Sec.  493.901 and 493.903. These 
technical and scientific responsibilities include, but are not limited 
to, processes for selecting appropriate target values to be included in 
challenges as part of the annual PT program or grading PT results, 
determining target values, reporting scores to CMS, and determining 
organisms included in microbiology PT samples. In an effort to clarify 
the intent of the proposed requirement, we are changing 
``administrative responsibilities'' to ``technical and scientific 
responsibilities'' in the provision being finalized at Sec.  
493.901(c)(8), previously proposed at Sec.  493.901(c)(9).
    Comment: While commenters agreed with the requirement proposed at 
Sec. Sec.  493.901(e) to allow HHS to require on-site visits as part of 
the initial approval of PT programs, they indicated the need for 
sufficient advance notice of an on-site visit. Also, there were two 
suggestions to use an independent third party if on-site visits were to 
be conducted.
    Response: We would coordinate the timing of the visit with the PT 
program and generally provide advance notice of the on-site visit. On-
site visits will be conducted by CMS, and not by a third party. As a 
result, we are finalizing the new requirement at Sec.  493.901(e) as 
proposed.
    Comment: We received comments concerning the requirement proposed 
at Sec.  493.901(f) that HHS may require a PT program to reapply for 
approval using the process for initial applications if significant 
problems are encountered during the reapproval process. While no 
commenters disagreed with the proposed requirement, one commenter 
requested that we use this option sparingly, and another commenter 
requested clarification on when this option would be used.
    Response: We intend to use this option cautiously and only when 
issues arise that we consider be significant, for example, complaints 
of quality issues related to the PT program. As a result, we are 
finalizing the new requirement at Sec.  493.901(f).
    Comment: Commenters suggested clarification was needed regarding 
the requirement proposed at Sec.  493.903(a)(3) that PT programs must 
not change or add any information on the PT result submission. They 
requested clarification on what data could not be changed, noting that 
some changes, such as adding or changing a method code, would not 
necessarily affect test results submitted but would be important for 
appropriate peer grouping. Commenters expressed concern that PT 
programs would not be able to add a methodology if inadvertently left 
off by the laboratory, thus affecting appropriate peer grouping. 
Commenters questioned if exceptions might be made if errors were made 
by the PT program and not the laboratory.
    Response: As explained in the proposed rule (84 FR 1536, 1547), it 
is not appropriate for a PT program to change or add information on the 
PT result submission from a laboratory, including, but not limited to, 
the testing methodology, results, data, or units. If a laboratory 
inadvertently enters the wrong methodology or omits a methodology, the 
PT program should not assume to know the correct methodology and make 
that change or addition. We would consider it acceptable for the PT 
program to enter the methodology in cases where the PT program form 
does not include the methodology used by the laboratory for testing and 
the laboratory has manually written the methodology on the result 
submission form. This would also apply to units of measure. Under no 
circumstances should a PT program change a laboratory's submitted 
result. It is the laboratory's responsibility to provide correct and 
complete information and to investigate and correct errors that lead to 
PT failures. As a result, we are finalizing the requirement at Sec.  
493.903(a)(3) as proposed.
    Comment: Commenters expressed concerns regarding the potential 
impact on laboratories and PT programs of the requirement proposed at 
Sec.  493.905(a) allowing HHS to withdraw the approval of a PT program 
at any point in the calendar year if the PT program provides false or 
misleading information required for program approval or if the PT 
program fails to correct issues identified by HHS related to PT program 
requirements.
    Response: We may withdraw approval of the PT program if HHS 
determines the PT program fails to meet any of the required criteria 
for approval. After we withdraw approval of a PT program, approval of 
the PT program would remain in effect for 60 days from the date of 
written notice to the PT program of this action. A PT program will be 
required to notify all of its participating laboratories of our 
withdrawal of approval within 30 days from the date of written notice 
to the PT program. We believe the 30-day notification by the PT program 
in this situation, and the additional 30 days before approval is 
withdrawn, gives laboratories sufficient time to enroll in an 
alternative PT program. PT programs may request reconsideration from us 
in accordance with subpart D of part 488 regarding the

[[Page 41209]]

withdrawal of approval if the false or misleading information or issues 
identified by us have been addressed within 60 days. We believe that 
the 60-day timeframe gives the PT programs sufficient time to mitigate 
any issues related to withdrawal of approval.
Summary of Final Actions
     We are finalizing the proposed changes to Sec. Sec.  
493.901(a), (c)(8), (e), (f), 493.903(a)(3), and 493.905.
     Based on comments received, we are not finalizing the 
proposed addition at Sec.  493.901(c)(6).

E. Proposed Changes to Microbiology PT (Sec. Sec.  493.911 Through 
493.919)

    Comment: Commenters suggested clarification is needed regarding 
methods or platforms for which PT is proposed to be required, 
specifically for laboratories that use molecular, nucleic acid 
amplification, mass spectrometry testing or next generation sequencing 
for microorganism identification and susceptibility testing in all 
microbiology subspecialties. A commenter also questioned whether PT is 
required only for FDA-cleared test systems. The commenters stated this 
clarification would help prevent confusion among laboratories.
    Response: PT is not required by method or specific technology for 
microbiology subspecialties (Sec. Sec.  493.911 through 493.919), 
including whether a test system is FDA-cleared, or analytes in non-
microbiology specialties or subspecialties (Sec. Sec.  493.921 through 
493.959). Regardless of the method, a laboratory uses for microorganism 
identification and susceptibility testing, PT is required for these 
categories of microbiology testing. When CLIAC deliberated on 
appropriate PT for microbiology, they suggested the inclusion of broad 
categories of testing performed in microbiology, rather than the types 
of services offered by laboratories, described in Sec. Sec.  493.911 
through 493.919, to allow flexibility for the inclusion of new 
technologies. Each laboratory needs to identify the method or test 
system used when submitting PT results for programs to properly grade 
the PT. If a laboratory performs microbiology testing for which PT is 
not available or required, they need to verify the accuracy of those 
procedures at least twice per year, as described at Sec.  
493.1236(c)(1). If available, voluntary PT may be a way the laboratory 
chooses to meet this requirement.
    Comment: Commenters supported the removal of the types of services 
offered by laboratories in each microbiology subspecialty and 
replacement of the types of services with general categories of testing 
for which PT is required. However, they had questions about the 
proposed option in bacteriology for detection of growth or no growth in 
culture media. They questioned whether this option was included or 
relevant for all microbiology subspecialties and all specimen types and 
whether it should be removed as an option under the category for 
identification of bacteria since bacteria are not identified when only 
growth is detected. A commenter also noted that this category may not 
be appropriate for cultures from normally sterile sites or those that 
are expected to contain normal flora. Another commenter requested for 
clarification of how this category would apply to urine colony counts. 
A commenter suggested changing the language in bacteriology to 
``presence or absence of bacteria without identification,'' with 
similar changes in other subspecialties. Another commenter suggested 
changing the language in bacteriology to ``growth or no growth in 
culture media or identification of bacteria to the highest level that 
the laboratory reports results on patient specimens.'' Other language 
changes suggested by commenters included revising this category to 
``growth or no growth of acid-fast bacilli'' in mycobacteriology and 
``growth of yeast, growth of mold, or specimen negative for fungi'' in 
mycology.
    Response: We recognize the need for clarification of this option 
based on the comments received. The option was proposed in bacteriology 
at Sec.  493.911(a)(1)(iv)(A); mycobacteriology at Sec.  
493.913(a)(1)(ii)(A); and mycology at Sec.  493.915(a)(1)(ii)(A) under 
the proposed categories for microorganism detection and identification. 
Similar language proposed for parasitology at Sec.  
493.917(a)(1)(ii)(A) specified detection of the presence or absence of 
parasites. This option was not proposed for virology. Specimen types 
are not included in any of the PT categories in microbiology and a 
challenge for growth or no growth, or presence or absence, was not 
proposed and may not be appropriate for all specimen types or sites, or 
appropriate as a response for all laboratories. It is one of two 
options included under the category of detection and identification of 
bacteria, mycobacteria, fungi and aerobic actinomycetes, and parasites, 
in the respective microbiology subspecialties. It was proposed as an 
option for laboratories that perform limited microbiology testing to 
detect the presence of microorganisms and then refer growth from 
culture or specimens containing the microorganisms detected to another 
laboratory for identification. In response to the question about 
applicability of this option for laboratories that perform urine colony 
counts, PT is not required for colony counts. If the laboratory 
performs identification of the bacterial growth, PT is required for the 
identification. If the laboratory performs the colony count only and 
refers the isolate for identification, an appropriate result for the PT 
challenge would be to report detection or growth of bacteria. In 
response to the suggestions for revisions to the language for this 
option in each of the subspecialties, after considering the suggestions 
from commenters, for clarification in this final rule we have changed 
the language at Sec.  493.911(a)(1)(iv)(A) to ``detection of the 
presence or absence of bacteria without identification.'' We changed 
the language at Sec.  493.913(a)(1)(ii)(A) to ``detection of the 
presence or absence of mycobacteria without identification, ``and at 
Sec.  493.915(a)(1)(ii)(A) to ``detection of the presence or absence of 
fungi and aerobic actinomycetes without identification.'' In 
parasitology, we added ``without identification'' to the end of the 
phrase currently at Sec. Sec.  493.917(a)(1)(ii)(A) and 493.917(b)(1) 
to be consistent with the other microbiology subspecialties. In these 
subspecialties, we also revised the performance criteria at Sec. Sec.  
493.911(b)(1), 493.911(b)(7)(i), 913(b)(1), 493.913(b)(5)(i), 
493.915(b)(5)(i), and 493.917(b)(5)(i) to correspond to these changes. 
For example, in bacteriology this change now specifies that the 
performance criterion is the correct detection of the presence or 
absence of bacteria without identification. This may be achieved when 
performing a culture and looking for bacterial growth or when using 
another test method that detects the presence of bacteria without any 
type of identification being performed.
    Comment: Two commenters recommended clarification of the proposed 
categories of direct antigen and toxin detection, with specific 
questions about the applicability of this category and which antigens 
or toxins are required in the subspecialties of bacteriology (Sec.  
493.911), mycobacteriology (Sec.  493.913), and mycology (Sec.  
493.915). One commenter questioned whether the intent of the proposal 
was to require PT for only Clostridium difficile toxin or also for 
other toxins in bacteriology. The same commenter requested 
clarification on which direct antigen tests are proposed to be required 
in mycology. Another commenter questioned whether antigen

[[Page 41210]]

detection was intended to be required for mycobacteriology, as it was 
not proposed and no programs currently offer this PT.
    Response: The requirement for PT for laboratories that perform 
direct antigen testing has been part of the CLIA regulations in the 
subspecialties of bacteriology and virology since PT was first required 
in 1994 and it was included as one of the required categories of 
microbiology PT in the proposed rule. As with other microbiology PT, 
the microorganisms for which it is required are not specified in the 
regulations. Rather, the regulations require that PT programs determine 
the reportable bacteria or viruses to be detected using direct antigen 
techniques. In this rule, required PT for direct antigen detection is 
included in bacteriology at Sec.  493.911(a)(1)(ii); mycology at Sec.  
493.915(a)(1)(i); parasitology at Sec.  493.917(a)(1)(i); and virology 
at Sec.  493.919(a)(1)(i). Required PT for toxin detection is included 
in bacteriology at Sec.  493.911(a)(1)(iii). As in the previous rule, 
the microorganisms for which direct antigen or toxin detection are 
required are not specified in the regulations. Rather, in all 
subspecialties for which this category is required, the regulations 
state the PT program determines the organisms to be reported by direct 
antigen or toxin detection. PT for direct antigen or toxin detection 
may be part of a combination module or offered as an individual five-
challenge module in each subspecialty. If a laboratory performs direct 
antigen or toxin testing for which PT is not available, they are 
required to verify the accuracy of those procedures at least twice per 
year, as described at Sec.  493.1236(c)(1).
    Comment: A few commenters addressed the proposed requirements for 
microbiology stains, with agreement that Gram stain PT should require 
bacterial morphology as well as gram-reaction. Commenters requested for 
clarification regarding the level of detail required for bacterial 
morphology as part of PT and whether Gram stain PT would be required 
when a Gram stain is performed as part of organism identification. 
Commenters also questioned the proposed inclusion of Gram stains and 
acid-fast stains in bacteriology and mycobacteriology, but lack of 
requirements for stain challenges in other microbiology subspecialties.
    Response: In this rule, we are finalizing the proposed requirement 
at Sec.  493.911(b)(1) that includes bacterial morphology when 
performing Gram stain PT. This may apply to either a Gram stain 
required as an individual challenge or as part of bacterial 
identification. PT program instructions specify which tests are to be 
performed on each sample, thus identifying which samples require Gram 
stains. Morphology should include the basic shape and arrangement of 
bacteria. However, as stated at Sec.  493.911(b)(1), the PT program 
determines the reportable staining and morphological characteristics to 
be interpreted by Gram stains. In response to the commenters who 
questioned whether PT was proposed for stains in mycology and virology, 
at this time, PT programs do not offer challenges for stains in these 
subspecialties. Thus, they were not proposed. In parasitology, although 
specific stains were not proposed as a required PT category, the sample 
types required at Sec.  493.917(a)(2) include PVA (polyvinyl alcohol) 
fixed specimens and blood smears, both of which are used in parasite 
identification. Because a variety of stains are used by laboratories to 
facilitate identification of intestinal, blood, and tissue parasites, 
and in some cases, parasites can be identified directly in wet mounts 
without using a stain, no stains were included for this microbiology 
subspecialty. Each laboratory participating in PT for parasite 
identification should follow the staining procedures they use for 
patient specimens.
    Comment: Commenters supported the removal of specific lists of 
microorganisms from the microbiology subspecialty requirements and 
replacement with general groups of organisms to be included over time. 
In addition, commenters requested clarification of the required groups 
in bacteriology, mycology, and virology. In bacteriology, one commenter 
suggested expansion of the groups to include Gram-negative cocci or 
coccobacilli, and another requested clarification of whether the groups 
of cocci include coccobacilli or diplococci. A third commenter 
suggested bacterial strains included in PT should be those routinely 
encountered in specimens. In mycology, two commenters expressed concern 
about inclusion of dimorphic fungi as a required category, noting that 
the majority require handling in a biosafety level 3 laboratory and are 
unable to be shipped. Comments pertaining to groups of organisms for 
virology recommended viral groups that must be included, and one 
organization questioned whether a PT program needed to offer all 
viruses and all specimen sources to be approved for virology PT. 
Specifically, the commenter questioned whether a program could offer PT 
challenges for susceptibility or resistance testing based on a single 
specimen source, such as urine. Another commenter requested for 
clarification regarding appropriate specimen sources to be included in 
virology modules and questioned whether combinations of viruses needed 
to be incorporated in a single PT sample.
    Response: The PT requirements for the microbiology subspecialties 
specify that the organisms included are those that are commonly 
occurring in patient specimens or are important emerging pathogens. The 
groups identified for each of the five subspecialties are general 
groups to be included over time and annually, if appropriate for the 
sample sources. They are not intended to be the only groups that could 
potentially be included. In bacteriology, Gram-positive or Gram-
negative coccobacilli or diplococci could be included as challenges in 
addition to, or as more specific subgroups of the individual 
morphologies listed for bacteriology at Sec.  493.911(a)(3). No changes 
are being made in this final rule to the bacteriology groups that were 
proposed. As stated by the commenters for mycology, dimorphic fungi 
were proposed at Sec.  493.915(a)(3)(ii)(C) as a group of organisms to 
be included in mycology over time and more specifically, required on an 
annual basis. We recognize the commenters concerns with the proposed 
inclusion of this group of fungi, some of which must be manipulated at 
a biosafety level 3. In response to these concerns, we have removed the 
dimorphic fungi from the groups of annually required organisms in 
mycology. However, over time, we encourage PT programs to include a 
variety of organisms in each subspecialty, as appropriate, to test a 
laboratory's ability to detect and identify the spectrum of organisms 
that might be found in patient specimens. In mycology, this may 
occasionally include dimorphic fungi, such as Sporothrix schenckii, 
that can be handled under biosafety level 2 conditions. In response to 
the questions about the PT requirements for virology at Sec.  
493.919(a)(3), the proposed rule did not specify that all viruses or 
specimen sources needed to be included for a PT program to be approved. 
However, it was proposed that if appropriate for sample sources 
offered, the types of viruses included annually must be representative 
of the groups of medically important viruses listed. Generally, with 
this rule, PT programs must continue to offer the same types of 
virology challenges and modules that have been offered in the past. 
Lastly, PT

[[Page 41211]]

samples containing combinations of viruses were not proposed and are 
not required in this final rule.
    Comment: Several commenters indicated that the proposed requirement 
in all microbiology subspecialties for laboratories to detect and 
identify organisms to highest level performed on patient specimens was 
unclear. One commenter recommended changing the description of the 
category for identification of bacteria to ``the highest level that the 
laboratory reports results on patient specimens.'' Two commenters 
suggested identification needed to be clarified as to whether the 
intent was presumptive or definitive identification and others 
questioned how this requirement should be applied with respect to 
identification at the genus or species level. The commenters stated 
more specific and better-defined criteria are needed, as well as the 
incorporation of language to allow for abbreviated reporting frequently 
used in reporting mixed cultures. They also questioned whether this 
information would need to be transmitted from PT programs to CMS and 
State agencies and one noted it would take time to implement this 
requirement. Another commenter stated it is the responsibility of 
inspectors to review patient reporting practices and not that of PT 
programs.
    Response: We agree that the language proposed in all subspecialties 
for identification of microorganisms to the highest level that it 
performs procedures on patient specimens may be unclear, and we agree 
that the revised description provided by the commenter earlier more 
clearly specifies that this requirement refers to how a laboratory 
reports results on patient specimens. As a result, we have incorporated 
the change suggested by the commenter and made conforming changes in 
this rule for all subspecialties at Sec. Sec.  493.911(b)(2), 
493.913(b)(2), 493.915(b)(2), 493.917(b)(2), and 493.919(b)(2). We 
expect that this will clarify that if a laboratory reports patient 
results to the genus level, that is the expectation for PT. Similarly, 
if a laboratory reports patient results to the species level, that 
would be the expectation for reporting patient results. In response to 
the question about incorporation of language to allow for reporting 
abbreviated results, if this is the practice for reporting results to 
the highest level on patient specimens, it may be an acceptable PT 
practice as well. In all subspecialties, PT programs determine the 
organisms that must be reported as part of their identification. We 
believe the delayed implementation of specific portions of this final 
rule will allow PT programs to incorporate updates needed for reporting 
results to CMS. We agree with the commenters who stated that it is the 
responsibility of laboratory inspectors to review patient reporting 
practices and not the responsibility of PT programs and this was part 
of a CLIAC recommendation made prior to the development of the proposed 
PT rule. It was not our intent that PT programs take on this 
responsibility and it was not included in the proposed rule.
    Comment: Multiple commenters supported the proposed changes to 
decrease the required percentage of mixed culture challenges from at 
least 50 percent to at least 25 percent in bacteriology, 
mycobacteriology, and mycology. The change, if finalized, would specify 
that at least 25 percent of the PT samples must contain mixtures of the 
principal organisms and appropriate normal flora.
    Response: We agree with the commenters and appreciate their support 
of these proposed changes. This is in alignment with a CLIAC 
recommendation stating such and was proposed at Sec. Sec.  
493.911(b)(1), 493.913(b)(1), 493.915(b)(1). We are finalizing these 
changes in this rule.
    Comment: Some commenters recommended changes to the microbiology 
subspecialties for which susceptibility or resistance testing PT was 
proposed to be required. A commenter noted that it would be difficult 
to comply with the requirement for susceptibility or resistance testing 
in mycology since samples are limited, there are few FDA-cleared 
methods or breakpoints for fungi, and there is extensive variability in 
the testing. Another commenter recommended that susceptibility or 
resistance testing may not be added to required PT in mycology and may 
be removed in mycobacteriology since few laboratories perform this 
testing. A third commenter stated the value of requiring PT for M. 
tuberculosis susceptibility testing is limited since programs often 
send out the same strain that is susceptible to all drugs tested. With 
respect to virology, a commenter disagreed with requiring 
susceptibility or resistance testing in this subspecialty and proposed 
requiring PT for viral loads. Another commenter indicated that since 
only one PT program currently offers antiviral susceptibility testing, 
that does not meet the specified criterion of requiring that three 
programs offer PT for an analyte or test, and it may not be required in 
virology. Finally, a commenter questioned whether a PT program should 
be required to offer susceptibility or resistance testing PT in 
virology if they offered other virology PT.
    Response: We agree with the commenters' reasons for suggesting that 
PT not be required for susceptibility or resistance testing in mycology 
and virology at this time. Therefore, we are removing the proposed 
requirements for inclusion of this category of required PT Sec.  
493.915(a)(1)(iii) for mycology and at Sec.  493.919(a)(1)(iii) for 
virology in this final rule. If this testing becomes less variable and 
PT availability increases in these subspecialties in the future, we may 
propose to include it in rulemaking at that time. In the meantime, if a 
laboratory performs susceptibility or resistance testing on patient 
specimens in mycology or virology, they are required to verify the 
accuracy of those procedures at least twice per year, as described at 
Sec.  493.1236(c)(1). Voluntary PT may be a way the laboratory chooses 
to meet this requirement. With respect to the requirement for 
susceptibility or resistance testing in mycobacteriology, we are aware 
that small numbers of laboratories perform this testing and subscribe 
to PT and that only one program currently offers susceptibility testing 
PT in mycobacteriology. We also recognize that PT programs are less 
likely to send out resistant strains of mycobacteria, especially M. 
tuberculosis, due to biosafety concerns when shipping or working with 
these organisms. For these reasons, in addition to the fact that 
mycobacteriology is unique in that only two PT events per year are 
required, we are removing the requirement at Sec.  493.913(a)(1)(iii) 
for susceptibility or resistance testing in mycobacteriology in this 
final rule. As stated previously, if a laboratory performs 
susceptibility or resistance testing on patient specimens in 
mycobacteriology, they are required to verify the accuracy of those 
procedures at least twice per year, the same frequency as required PT 
in this subspecialty. Laboratories may choose to subscribe to voluntary 
PT as a way to meet the requirement or they may use another mechanism 
to meet the requirement that does not include shipping strains of 
organisms that require special precautions.
    Comment: Commenters questioned or requested clarification of the 
proposed requirements specified for antimicrobial susceptibility or 
resistance testing, including clarification of the definition or intent 
of resistance testing, questioning whether it meant testing for 
resistance mechanisms or markers for specific organisms. One commenter 
stated clarification was needed as to whether susceptibility testing is 
optional if a laboratory performs

[[Page 41212]]

identification. Another commenter suggested the language for this 
category of PT in bacteriology be clarified to state ``antimicrobial 
susceptibility or resistance testing of select bacteria.''
    Response: The category of antimicrobial susceptibility or 
resistance testing was included in the proposed rule in for the 
subspecialties of bacteriology at Sec.  493.911(a)(1)(v); 
mycobacteriology at Sec.  493.913(a)(1)(iii); mycology at Sec.  
493.915(a)(1)(iii); and virology at Sec.  493.919(a)(1)(iii). 
Resistance testing was included in this proposed category as it was 
previously recommended by CLIAC to be required along with 
susceptibility testing. As discussed in the previous comment, the 
proposed requirement for susceptibility or resistance testing in 
mycobacteriology, mycology, and virology has been removed from this 
final rule. With respect to the proposed requirement for this category 
in bacteriology, we agree with the commenters that the interpretation 
of ``resistance testing'' may not be clear, and that in some cases, 
bacterial resistance may be determined as part of an organism 
identification. For these reasons, we have removed resistance testing 
from the required category proposed in bacteriology and in this final 
rule we are requiring antimicrobial susceptibility testing of select 
bacteria, as suggested by the commenter, at Sec.  493.911(a)(1)(v), 
since antimicrobial susceptibility testing is not performed on every 
bacterium that is isolated in a culture and PT programs specify which 
challenges require that susceptibility testing be performed. This also 
addresses the comment suggesting a change in the description of this 
bacteriology category for clarification. If laboratories perform 
resistance testing separate from bacterial identification, they are 
required to verify the accuracy of those procedures at least twice per 
year, as previously stated, and may enroll in voluntary PT to do so. In 
response to the recommended clarification of whether susceptibility 
testing is optional when a laboratory performs identification, 
laboratories must follow PT program instructions when determining which 
tests to perform on a microbiology sample. The programs must clearly 
identify which samples require that susceptibility testing be performed 
on bacteria that are identified and those results reported for PT 
purposes.
    Comment: Several commenters agreed with the proposed increase in 
the number of required susceptibility or resistance testing challenges 
from one to two per event in all microbiology subspecialties except 
parasitology, where PT for susceptibility testing is not required. They 
indicated that increasing the number of challenges and requiring one 
Gram-positive and one Gram-negative challenge per event in bacteriology 
would help identify issues with patient testing. Other commenters 
disagreed with this proposed change, expressing concerns that this 
requirement would provide too much information to laboratories about PT 
sample content and make the PT results more predictable. One commenter 
stated that including two susceptibility challenges per event lacked 
value and relevance. Others suggested that requiring a mixture of 
challenges throughout the year was preferred over the requirement to 
include one Gram-positive and one Gram-negative challenge per event.
    Response: We agree with the commenters who supported the proposed 
change to increase the number of required susceptibility or resistance 
challenges to two per event and are finalizing that change in this rule 
at Sec.  493.911(a)(4). This change was recommended by CLIAC, and we 
believe it will provide a better assessment of laboratory testing 
performance over time. We also agree with the commenters who suggested 
that we should not specify a predictable pattern of susceptibility 
testing challenges in bacteriology, requiring that each event must 
include one Gram-positive and one Gram-negative challenge. As a result, 
in this rule, we are revising the requirement to indicate that each 
year, a minimum of two samples per testing event of susceptibility 
testing challenges must include a mixture of Gram-positive and Gram-
negative challenges.
    Comment: A PT program commented on the proposed requirements to 
change scoring for the microbiology subspecialties by including 
separate category scores in addition to the overall subspecialty 
scores. The program inquired about the intent of this proposed change 
and suggested that it would increase the complexity of determining 
scores and it may be especially challenging to score laboratories that 
perform a mixture of detection and identification procedures. The 
commenter also noted the proposed scoring method would give PT programs 
discretion in the interpretation of the requirement which could result 
in laboratories choosing the program that uses the most advantageous 
method. The commenter advocated for simplifying the subspecialty 
scoring process rather than increasing complexity for efficiency and 
increasing the value to laboratories.
    Response: The four categories of testing proposed for microbiology 
PT were recommended by CLIAC to replace the types of laboratory 
services that are part of the current regulations. The types of 
services guided the scoring of microbiology subspecialties since there 
are no specific analytes in this laboratory specialty. However, since 
only a single score is given for each subspecialty, many times 
representing a combination of results for different types of testing, 
it is not possible for laboratory surveyors to readily determine if a 
laboratory is having problems with one area of their microbiology 
testing. No changes were made to the scoring process for microbiology 
in the proposed rule other than aligning the requirements for 
evaluation of a laboratory's performance at Sec. Sec.  493.911(b) 
through 493.919(b) to be consistent with the categories of testing and 
facilitate the identification of problems in any one of the categories.
Summary of Final Actions
     We are finalizing the proposed revisions at Sec. Sec.  
493.911 through 493.919 by removing the types of services listed for 
each microbiology subspecialty and inserting a more general list of 
organisms.
     We are finalizing the proposed revisions at Sec. Sec.  
493. 911(a), 493.913(a), and 493.915(a) that are related to growth or 
no growth and mixed culture requirements (50 percent to 25 percent).
     We are finalizing the proposed performance criteria 
revisions at Sec. Sec.  493.911(b), 493.913(b), 493.915(b), 493.917(b), 
and 493.919(b).
     We are finalizing the proposed addition of ``without 
identification'' to the end of the phrase currently in the subspecialty 
of parasitology at Sec.  493.917(a)(1)(ii)(A) to be consistent with the 
other subspecialties.
     We are finalizing the proposed revised requirement at 
Sec. Sec.  493.911(b)(2), 493.913(b)(2), 493.915(b)(2), 493.917(b)(2), 
and 493.919(b)(2) to clarify and emphasize that laboratories should 
detect and identify organisms to the highest level that they report 
results on patient specimens.
     We will amend Sec. Sec.  493.911(b)(1), 493.913(b)(1), 
493.915(b)(1), 493.917(b)(1), 493.919(b)(1) to clarify that for the 
purpose of achieving consensus, PT programs must attempt to grade using 
both participant and referee laboratories before determining that the 
sample is ungradable.
     We are finalizing the proposed revisions to Sec.  
493.911(a) through (b) related to Gram stains, direct antigen 
detection, bacterial toxin detection, and performance and scoring 
related to

[[Page 41213]]

direct antigen and bacterial toxin detection for the subspecialty of 
bacteriology.
     We are finalizing the proposed addition to Sec.  
493.915(a) related to requiring direct antigen testing for the 
subspecialty of mycology.
     We are finalizing the proposed addition to Sec.  
493.917(a) related to requiring direct antigen testing for the 
subspecialty of parasitology.
     We are finalizing the proposed revision to Sec.  
493.919(a) related to requiring direct antigen testing for the 
subspecialty of virology.
     We are removing the reference to resistance testing in the 
subspecialty of bacteriology and have removed references to 
``resistance testing'' in the requirement for antimicrobial 
susceptibility testing of select bacteria at Sec.  493.911.
     We are not finalizing the proposed requirements for PT of 
antimicrobial susceptibility and resistance testing in the 
subspecialties of mycobacteriology, mycology, and virology and have 
removed the requirement at Sec. Sec.  493.913, 493.915, and 493.919.

F. Proposed Changes to PT for Non-Microbiology Specialties and 
Subspecialties (Sec. Sec.  493.921 Through 493.959)

1. Required Analytes
    Comment: Several commenters agreed that the list of required 
analytes should be updated. Some commenters stated that the process for 
analyte inclusion and removal was thorough, understandable, and 
transparent. One commenter stated the inclusion threshold for new 
analytes that only included three PT programs, rather than four, could 
result in an unfair market advantage, raise PT costs for laboratories, 
or result in logistical difficulties in obtaining PT.
    Response: In response to the comments, we reviewed our analyses and 
determined that there were no proposed analytes that would not have 
made the requirement for being offered by at least four PT programs, as 
was suggested by the commenter. We believe that the fact that there are 
already at least three programs available to choose from for each new 
analyte or test gives laboratories several options and should not 
result in increased costs or logistical difficulties in obtaining PT. 
All PT programs received notification of the proposed analytes or tests 
at the same time when the proposed rule was published. Whether a PT 
program elects to offer a particular analyte is a business decision of 
the PT program, and outside of our purview.
    Comment: A small number of commenters mentioned concerns about the 
possibility that either inclusion of the PT analytes or the ALs we 
proposed would have a negative impact on access to testing. A few 
commenters suggested that for the ALs proposed for some analytes, some 
existing test systems would not meet the new requirements. For example, 
one manufacturer stated that the proposed ALs for creatine kinase 
isoenzymes may be challenging for some testing platforms to meet. A 
similar comment was made for proposed ALs for troponin I and 
hematocrit.
    Response: During the phase in period, manufacturers will have time 
to improve test accuracy, and laboratories will have time to switch to 
higher accuracy test methods if those they use do not provide results 
that are able to meet the criteria for acceptable performance specified 
in the regulations. Clinicians and patients should be able to expect 
accurate testing, and assuring overall accuracy is the goal of 
performing PT. Therefore, these changes should drive the health care 
system toward more accurate methods. We have no reason to believe that 
access to testing will be impacted.
    Comment: Several commenters supported the list of analytes that 
were proposed for addition and deletion, and commenters supported the 
process we used for determining the list of analytes for which PT is to 
be required. No commenters questioned any of the proposed new analytes. 
However, one commenter stated that a current analyte, T3 uptake, should 
be deleted because it lacked clinical utility. An accreditation 
organization and an individual commented that determination of creatine 
kinase (CK) MB fraction by electrophoresis should be discouraged, and 
therefore, it should be excluded from the required PT for creatine 
kinase isoenzymes. Rather, the commenters noted that PT should only be 
required for laboratories that use immunochemical methods when testing 
for this analyte. Some commenters recommended inclusion of analytes 
that we had considered but decided not to include. One commenter 
suggested that we require PT for several immunosuppressant drugs for 
which PT is not currently required.
    Response: We had initially considered all the analytes that 
commenters recommended for either inclusion or deletion, but the 
suggested analytes did not meet one or more of our inclusion or 
deletion criteria. Both the inclusion and deletion processes, which 
were described in the proposed rule, were based upon per-analyte 
estimates of the availability and the number of programs already 
offering PT, the nationwide volume of patient testing, the impact on 
patient or public health of offering PT, and the cost and feasibility 
of PT implementation. We did not propose deletion of T3 uptake because 
test volumes were above the threshold for consideration. With respect 
to the suggestion to discourage laboratories from using electrophoretic 
methods to test for CK-MB isoenzymes, the method used is not a basis 
for requiring or not requiring PT for any test or analyte. Each 
laboratory needs to identify the method or test system used when 
submitting PT results for programs to properly grade the PT. To the 
extent that test results are used for clinical decision making, the 
test results should be accurate. The immunosuppressant drugs that were 
suggested were not done in sufficient volumes to meet the threshold for 
consideration in the proposed rule, so they were not proposed to be 
required.
    Comment: For a few analytes that can be detected or quantified in 
more than one way, some commenters requested clarification concerning 
which analyte would require PT. For example, a commenter questioned if 
PT was proposed to be required whether LDL cholesterol was calculated 
or measured directly. Several commenters requested clarification 
concerning whether drugs were to be measured in total or free forms. 
One commenter mentioned a need to specify the sample type that should 
be tested if the analyte can be tested in more than one type of body 
fluid.
    Response: For LDL cholesterol, which can be measured both directly 
and as an estimation based on other measured lipids, PT is only 
required for directly measured (not calculated) LDL cholesterol. For 
all drugs, we intend that the measured form must be total drug. For the 
specialty of chemistry, in subpart I the sample types for which PT is 
required are specified for each under each subspecialty, at Sec.  
493.931(b) for general chemistry, Sec.  493.933(b) for endocrinology, 
and Sec.  493.937(b) for toxicology. If a laboratory performs patient 
testing on other sample types than those listed, they are required to 
verify the accuracy of testing with those alternative sample types at 
least twice per year, as described at Sec.  493.1236(c)(1). If 
available, voluntary PT may be a way the laboratory chooses to meet 
this requirement.
    Comment: A few commenters requested clarification of what should be 
considered high sensitivity C-reactive protein, as opposed to 
traditional C-reactive protein, as included in the

[[Page 41214]]

proposed rule. A related comment suggested that we should require PT 
for all assays for C-reactive protein.
    Response: Although traditional C-reactive protein has been used as 
a general marker of inflammation for many years, it did not meet the 
threshold for inclusion as a required PT analyte. In this rule we are 
finalizing the proposed PT requirement for high sensitivity C-reactive 
protein and we appreciate the need to define which test methods would 
be considered ``high sensitivity'' testing. High sensitivity C-reactive 
protein concerns testing related to cardiac ischemia, either for frank 
cardiac events or for risk stratification, which requires more 
sensitive test methods to detect lower concentrations. We are deferring 
to laboratories to know whether their assay is a high sensitivity 
method used to detect cardiac pathology, or the traditional, less 
sensitive C-reactive protein. PT programs must label their PT offerings 
accordingly.
    Comment: One commenter suggested that we should specify the N-
terminal region of pro-B-natriuretic peptide (BNP), which was included 
as a required analyte in the proposed rule because this is the epitope 
usually detected by antibodies used in most test methods.
    Response: We agree with the commenter that the N-terminal region of 
pro-B-natriuretic peptide (BNP) is the part of the peptide that is 
usually measured, but we did not want to restrict the requirement for 
PT. Therefore, in this rule we are finalizing the name as proposed: 
proBNP.
2. Scoring and Acceptance Limits
    Comment: With respect to scoring and ungradable samples, one 
commenter requested clarification about how performance on an analyte 
was determined for a PT event when one of the PT samples was not able 
to be graded. The commenter questioned what the denominator of graded 
samples would be. An accreditation organization agreed with our 
proposal to require PT programs to attempt to reach consensus using 
both laboratory and referee laboratories before deciding a sample is 
ungradable due to lack of consensus.
    Response: If a sample for a particular PT event is ungradable, for 
example, because consensus could not be reached, it is still considered 
to be part of the denominator of five PT samples for that event, and in 
this case, the laboratory is given credit for passing the challenge. 
Therefore, if one of the remaining PT samples in the event is missed, 
the event score is 80 percent, and the event score is ``satisfactory'' 
for the majority of required PT.
    Comment: Several commenters stated that the process used for 
simulating the impact of scoring PT using several alternative ALs to 
determine the optimal limit to require was unclear.
    Response: As discussed in the proposed rule, we requested PT 
programs to examine the impact of various ALs on their aggregated 
sample failure rates, using the peer grouping approaches they had 
previously used. A number of the PT programs provided simulated 
results, applying various possible percentage-based ALs to actual 
results from previous PT events, and were able to help us select 
appropriate ALs. We selected ALs using a target miss rate (per sample) 
in the 1 to 2 percent range. Our intent was to assure that the ALs 
would work across the clinically important range and not 
inappropriately fail results that were accurate for clinical decision 
making. Therefore, we examined error rates at all concentrations that 
PT programs used throughout the 2 years of PT data they shared with us.
    Comment: We received a number of comments related to the proposal 
to use percentage-based ALs whenever possible. While some commenters 
supported the proposed changes, others suggested changes to specific 
proposed ALs for both current and newly proposed analytes. Generally, 
these comments concerned whether the proposed limits would be workable 
across the clinically important measurement interval for all test 
methods and platforms. In almost all cases, the comments recommended 
less stringent ALs, either across the entire analytical measurement 
range or specifically at low concentrations, where test methods are 
generally less accurate. Commenters pointed out that unless there is 
allowance for low concentrations, PT programs would be discouraged from 
using PT samples with low concentrations, to the detriment of assuring 
accurate testing across the analytical range. Supporting this, some 
commenters stated that it is not clinically important to be as accurate 
as the percentage-based limits would require. Commenters suggested that 
we use a combination of a percentage and a concentration limit for 
certain analytes, such that PT samples with relatively low 
concentrations would be more fairly assessed. In some cases, commenters 
recommended a concentration limit that differed from a concentration 
limit we had proposed. A small number of commenters were generally 
concerned about moving from familiar 3 SD-limits to percentage based 
ALs for some currently required analytes.
    Response: In response to commenters' concerns about the use of 
percentage limits when scoring PT analytes at low concentrations, in 
this final rule, we are including ``concentration limits'' such as are 
already used for glucose and some other analytes for many newly 
required analytes and some previously required analytes. When adding 
concentration limits and using combined ALs, programs are directed to 
score with whichever of the specifications is more tolerant, allowing 
for fairer and more realistic ALs that will allow PT programs to cover 
the clinically important range of results. We re-examined previously 
acquired simulation data from PT programs and have added concentration 
limits for 13 analytes. Specifically, we created concentration 
thresholds for alanine aminotransferase, aspartate aminotransferase, 
cholesterol (high density lipoprotein), CK-MB isoenzymes, glucose, 
carcinoembryonic antigen, human chorionic gonadotropin, vitamin B12, 
acetaminophen, carbamazepine, lithium, phenobarbital, and salicylate. 
Concerning the switch from current 3 SD limits to percentage-based 
limits, we believe that the new ALs will be workable, fair, and 
clinically relevant. As stated in the proposed rule, ALs based on 
analytical variability within a peer group, such as the use of 3 SD 
limits, are ill-suited to know whether testing results are sufficiently 
accurate for clinical purposes.
    Comment: Two commenters noted that CLIA ALs have been used in ways 
other than their intended purpose of identifying laboratories with 
unacceptable performance. One commenter noted that ALs have been used 
as goals for ideal performance, for example, setting quality control 
acceptable limits. Another commenter pointed out that ALs have been 
used for verifying analytical performance, for example, accuracy.
    Response: We agree with the comments and reemphasize that ALs must 
not be used as the criteria to establish performance goals in clinical 
laboratories. Goals for accuracy and precision must be based upon 
clinical needs and manufacturer's FDA-approved or -cleared labeling; PT 
performance is not the best assessment of these. Proficiency testing is 
intended to identify laboratories that are not performing with 
acceptable analytic accuracy; it is not intended, nor suited, to 
provide goals for analytical accuracy or clinical performance.

[[Page 41215]]

    Comment: Many commenters stated the proposed AL for hemoglobin A1c 
(HbA1c) was too loose and not reflective of the testing accuracy of 
current test methods. Many individuals and organizations commented that 
the AL should be 6 percent, and several recommended lowering the limit 
to 5 percent. Several comments requested that CLIA ALs should not 
``change'' from the current 6 percent, despite the fact that HbA1c is 
currently not a CLIA-required PT analyte, and therefore, no ALs are 
specified in the regulations. Many commenters expressed concerns that 
using a threshold higher than 6 percent would in some way subvert the 
substantial progress made by the National Glycohemoglobin 
Standardization Program (NGSP), working collaboratively with test 
method manufacturers, to improve accuracy of HbA1c testing. Commenters 
suggested that manufacturers would allow the accuracy of their test 
methods to deteriorate if CLIA added HbA1c with an AL as loose as 10 
percent. A PT program proposed that we use an AL of 10 percent for non-
commutable PT materials and a limit of 6 percent for commutable 
(accuracy-based) PT materials. Another PT program commented in favor of 
a 10 percent limit, noting that non-commutable PT materials may be less 
accurate with certain test methods and, moreover, PT is not intended to 
directly reflect accuracy needed for clinical testing.
    Response: We appreciate the importance of HbA1c for diagnosis and 
monitoring patient management, and the need for testing accuracy that 
is sufficient to meet clinical needs, and we support the progress that 
continues to be made to improve the accuracy of HbA1c testing. As 
mentioned in the previous comment, CLIA PT ALs are intended to 
identify, and hopefully remediate, laboratories that are not providing 
results as accurate as their peers. CLIA PT ALs should not be used as 
accuracy goals by manufacturers or by standardization initiatives such 
as the NGSP. CLIA should not impose a requirement that limits access to 
critically important patient testing, especially if it is based on PT 
results that may not reflect the accuracy of patient testing.
    One PT program has demonstrated progressive improvements in 
accuracy of testing by laboratories enrolled in their accuracy-based PT 
program, which uses commutable patient samples. We are aware that, over 
time, the program has incrementally tightened their ALs for the 
accuracy-based PT. This progress has been possible without CLIA 
requiring PT for HbA1c, and therefore, adding a PT requirement for 
HbA1c should not impede further progress in the future. Accreditation 
organizations have the flexibility to require their laboratories to 
meet a more stringent requirement than CLIA. They also have the option 
of using the CLIA limit and using a second, more stringent, AL for 
educational purposes. Either approach would allow these organizations 
to continue to tighten the limits for HbA1c for their accredited 
laboratories. We acknowledge the importance of standardization 
programs, like the NGSP, having the latitude to continuously adjust 
their accuracy goals to monitor and encourage improvements in the 
accuracy of HbA1c testing. We do not believe that a CLIA AL that is 
looser than the limit in use by the accuracy-based PT program would 
cause manufacturers to allow testing accuracy to deteriorate, as many 
commenters have suggested.
    The AL adopted in CLIA regulations must not be too tight for 
laboratories that do not participate in an accuracy-based PT program 
that uses commutable PT materials. In simulation studies performed 
before issuing the proposed rule, laboratories using non-commutable PT 
samples had poorer performance, especially when scoring using any AL 
less than 10 percent. This might have occurred because laboratories not 
enrolled in accuracy-based PT use different test methods or because the 
PT they use is non-commutable. CLIA does not specify whether 
laboratories are required to participate in PT based on whether it is 
commutable or non-commutable. The same AL apply regardless of the PT 
samples' commutability.
    After analyzing the comments received in response to the proposed 
rule, we requested the PT programs that offer HbA1c to simulate results 
that would be obtained if they used 5 percent, 6 percent, 8 percent, 
and 10 percent as the AL. We requested programs to indicate miss rates 
and unsatisfactory rates based upon different HbA1c concentrations in 
their materials, and to disclose performance based upon their testing 
platform or peer groups used. Based upon these more recent simulated 
results, we found that it will be possible to use a tighter AL than 10 
percent. After this analysis, we are setting the AL for HbA1c at 8 
percent in this final rule. The performance improvements we saw between 
the first and later simulations may reflect improvements in the 
accuracy of testing for HbA1c.
    Comment: Commenters stated that rather than using the proposed AL 
of 20 percent for LDL cholesterol, we should require an AL of 12 
percent, which is the accuracy target used by the National Cholesterol 
Education Program.
    Response: Because the commenters suggested an AL tighter than was 
proposed, we requested PT programs to simulate the impact of using that 
limit. Based upon reanalysis of new data shared by PT programs, we 
confirmed that the proposed AL of 20 percent is appropriate for scoring 
PT for LDL cholesterol, and we are finalizing that limit in this rule.
    Comment: With respect to PT for blood lead, we proposed a change 
from the current AL of 4 mcg/dL or 10 percent (greater) to 
2 mcg/dL or 10 percent (greater). One commenter supported 
the proposed AL, consistent with efforts to improve the ability of 
laboratories to detect very low concentrations of blood lead in patient 
specimens. Conversely, another commenter stated that the reduction of 
the concentration AL from 4 mcg/dL to 2 mcg/dL would result in more 
instances of nonconsensus, which would result in more ungraded samples 
and events. Another commenter expressed concerns about the impact of 
the proposed limits on failures for certain testing platforms.
    Response: We agree with the commenter who emphasized the public 
health importance of the need for accuracy at low concentrations of 
blood lead, to detect and prevent cases of childhood lead poisoning, 
and are finalizing the proposed AL for blood lead at 2 mcg/dL 10 percent (greater) in this rule. We appreciate the commenters' 
concerns, however, one outcome of more stringent ALs may be that 
laboratories switch to test methods that are more accurate across the 
range of testing and better able to meet clinical needs. We believe 
that manufacturers of analytical platforms that may fail to achieve 
consensus, or otherwise perform poorly, will improve their accuracy 
during the phase-in period. To address concerns regarding unintended 
consequences that may increase health disparities, we will monitor 
changes in PT participation for all analytes after this rule becomes 
effective as this is required as part of PT oversight under CLIA. This 
includes the methods used for testing each PT analyte required by CLIA.
    Comment: A few commenters provided suggestions related to the 
addition of troponin I and troponin T as required analytes in routine 
chemistry. One commenter was concerned that adding troponins to the 
required list for PT may potentially limit access to point-of-care 
cardiac triage testing of potential cardiac events in rural settings. 
The

[[Page 41216]]

same commenter also suggested that the ALs for troponin I and troponin 
T should be expanded to 40 percent, with no suggested 
changes to the associated concentration limits. A couple of commenters 
suggested that the same, percentage-based AL would work for both 
generic and high sensitivity troponins. A small number of commenters 
suggested that we should require PT for high sensitivity troponin 
assays in addition to traditional troponin assays.
    Response: Troponin I and troponin T are used to make decisions 
about the use of lifesaving, yet not risk-free, interventions, such as 
cardiac catheterization and therapeutic thrombolysis. Therefore, it is 
important that such testing be both accessible and accurate. We believe 
that requiring PT for the troponins is important and must not inhibit 
access to testing. We reviewed our simulation data to see if the same 
concentration limit would work for both troponin I and T. We determined 
that we must use the proposed, different ALs, and, therefore, are 
finalizing the AL for troponin I as 0.9 ng/mL or 30 percent 
(greater) and for troponin T as 0.2 ng/mL or 30 percent 
(greater). At the time we proposed these changes, troponin I and T were 
not frequently tested as ``high sensitivity'' analytes, that is, at 
very low limits of detection. Also, there were not enough PT program 
offerings to meet our threshold for inclusion for high sensitivity 
troponins. Therefore, we are not requiring PT for ``high sensitivity'' 
troponin I or T.
    Comment: A few commenters stated that some proposed percentage-
based ALs were too tight, regardless of whether a concentration 
threshold was included. Commenters stated that the proposed percentage 
ALs for immunoglobulin A (15 percent), immunoglobulin E 
(15 percent), amylase (15 percent), and 
leukocyte count (5 percent) were too tight. The commenters 
recommended ALs be set at 20 percent for immunoglobulin A, 
25 percent for immunoglobulin E, and 10 percent 
for leukocyte count. No recommendation was provided for amylase.
    Response: We re-examined simulation data that had been submitted by 
PT programs and revised percentage limits as appropriate. Specifically, 
in this rule we are finalizing the AL for immunoglobulin A to 20 percent, amylase to 20 percent, and leukocyte 
count to 10 percent. We determined that adding a 
concentration limit for these analytes was not necessary or adequate to 
make the AL workable at a lower concentration. For immunoglobulin E, we 
did not determine that it was necessary to increase the AL to 25 percent; therefore, we are finalizing the AL for 
immunoglobulin E in this rule at 20 percent.
    Comment: Some commenters expressed concerns related to proposing 
ALs based on allowable total error derived from estimates of biological 
variability (BV). There was a comment that the use of BV data was in 
flux at this time. One commenter noted that estimates of BV that we 
used may be incorrectly wide due to errors in the way estimates were 
made, specifically that they may overestimate BV because the results 
are based upon analytical test methods that have inherent variability. 
One commenter stated that BV cannot be directly related to clinical 
outcomes. The same commenter stated that when setting ALs both BV and 
state-of-the art performance should be considered.
    Response: We appreciate the concerns expressed and note that the 
ALs we proposed were not based strictly on estimates of BV. Moreover, 
we are aware that the field of estimating BV data has changed in the 
last few years. However, any impact of suboptimal estimations of BV on 
the ALs we proposed was likely negligible because we always tested 
potential ALs using simulations. ALs that were too tight to be workable 
were eliminated even if they were not as stringent as our estimates of 
BV might have suggested were necessary. In other words, consistent with 
one of the comments, we used state-of-the-art performance, demonstrated 
through simulations, to finalize the proposed ALs. In some cases, we 
showed through simulations that it was possible to use ALs that are 
tighter than the ``minimal'' threshold based upon estimates of BV and 
in these cases we used a somewhat tighter AL, but only if the data from 
PT programs supported the tighter limit. As a result, changes in the 
estimates of BV we used would not have affected our proposed ALs.
    After re-examining the literature, we reconfirmed that BV is the 
only tenable approach to establishing new limits. We agree that 
clinical outcomes may not be reflected in BV data, but the preferred 
outcomes studies were not available to us.
    Comment: Commenters generally favored the proposal to require 
separate PT for cell identification and differentials rather than 
including an option to participate in PT for one or the other. It was 
pointed out that the results can be used for different purposes in 
patient treatment. There were questions, however, questioning whether 
there should be separate scores for cell identification and 
differentials or if they should be averaged. One commenter recommended 
that the three standard deviation criteria for acceptable performance 
for differentials should be changed to a percentage-based criterion and 
another suggestion was made to include 1.0 (whichever is 
greater) for low target values or absolute values (that is, basophils). 
An additional commenter requested clarification as to whether PT would 
be required for both manual and automated flow through differentials 
for laboratories that use platforms that can report flow through 
differentials.
    Response: We appreciate the support from commenters who recognized 
the need to recognize cell identification and differentials as two 
separate analytes and are finalizing that change in this rule. As 
separate analytes they may be scored individually. We are finalizing 
the criteria for acceptable performance for both analytes in this rule. 
We are not changing the criterion for differentials to percentage-based 
because we have no BV data on which to base that change. As such, we 
are also not including the 1.0 option for low target 
values. In response to the question regarding PT requirements for 
laboratories that perform both manual and automated flow through 
differentials, a laboratory should perform PT in the same manner as 
they perform testing on patient specimens. PT is required for the 
primary method of testing used for patient testing.
    Comment: A few commenters supported the proposal to change the 
consensus requirement for cell identification from 90 percent to 80 
percent. One commenter requested for clearer justification for the 
change.
    Response: This change was proposed because it is not possible to 
score 90 percent on a 5-challenge PT panel. We are finalizing the 
change in this rule.
    Comment: An accreditation organization made several suggestions 
about how standard deviations should be calculated when they are 
required as ALs for white blood cell differentials. For peer group 
sizes of 20 or more, they recommended that we continue to require 
elimination of outliers before calculation of the standard deviation. 
The commenter stated that when the peer group size is between 5 and 19 
laboratories, robust methods as described in ISO 13528, ISO Guide 35, 
or ASTM E-691, should be used. They recommended that, alternatively, 
the standard deviation could be an average standard deviation 
determined from previous rounds of PT, calculated according to ISO 
13528. They also noted that mention of 3 SD to set ALs should

[[Page 41217]]

be removed from parts of the regulation that no longer include 3 SD 
limits.
    Response: As mentioned by the commenter, this final rule includes 
only one analyte with a three standard deviation limit. We agree that 
this recommendation would allow more accurate estimates of 3 SD ALs for 
relatively small peer group sizes. We also agree that robust 
statistical methods must be used to calculate the standard deviations 
when the peer group size is between 5 and 19 laboratories. However, we 
are not specifying the statistical approach that needs to be used. We 
appreciate the commenter's suggestion to remove reference to 3 SD ALs 
in relevant sections of this final rule and have done so in Sec. Sec.  
493.931(c)(2) and 493.933(c)(2).
    Comment: A few commenters recommended that the international 
normalized ratio (INR) should be listed as a separate analyte in the 
specialty of hematology, the same way blood cell counts and white blood 
cell differentials are separate analytes, rather than including INR as 
a mechanism for reporting prothrombin time results, as was proposed. 
The commenters agreed that laboratories should report prothrombin time 
results in seconds, as an INR, or both as appropriate, in the same way 
that they report patient results. Commenters also stated that 
separating the prothrombin time and INR would allow for separate ALs 
for each of them.
    Response: It is important for laboratories to report PT results the 
same way that they report patient results. If patient results are 
reported in seconds or as INR results, laboratories should report the 
same way to PT programs. If the laboratory reports patient results in 
both seconds and as an INR, they should report both to PT programs. The 
AL for prothrombin time at 15 percent is applicable for 
both seconds and INR. When we referenced ``directly measured INR'' in 
the preamble to the proposed rule, we were referring to those devices 
that internally calculate and display the INR value rather than giving 
a value in seconds. The 15 percent AL for INR applies regardless of how 
it is derived.
    Comment: Two commenters remarked on the proposed change to the 
criteria for acceptable performance of unexpected antibody detection in 
immunohematology from 80 percent to 100 percent accuracy. While one 
commenter agreed with this proposed change, the other disagreed. The 
opposition was concerned with the possibility that laboratories that 
use less sensitive, but safe, methods could be penalized, and it could 
limit patient access to care.
    Response: We believe that the criteria for acceptable performance 
for unexpected antibodies should be 100 percent rather than 80 percent. 
We are finalizing this change because it is critical for laboratories 
to detect any unexpected antibody when crossmatching blood to protect 
the public health and not impact patient care. It is important that 
antibodies are detected to lessen the possibly of a transfusion 
reaction due to incompatible blood products.
    Comment: Concerning appropriate units for reporting PT results or 
some other aspect of the AL, some commenters noted that we 
inadvertently deleted titers for some ALs. It was pointed out that for 
some analytes we incorrectly suggested that the AL should be 
qualitative. Some commenters noted inaccuracies in the units we used 
for quantitative analytes.
    Response: We appreciate the commenters careful examination of the 
proposed limits and we made appropriate adjustments that are now 
reflected in the final rule. In response to comments about proposed 
units for reporting PT results, unintentional uses of incorrect units 
have been corrected in this final rule.
Summary of Final Actions
     We are finalizing the proposed revision at Sec. Sec.  
493.923(a), 493.927(a), 493.931(a), 493.933(a), 493.937(a) and 
493.941(a) to remove the option that PT samples ``at HHS option, may be 
provided to HHS or its designee for on-site testing.''
     We are finalizing the proposed addition of 29 analytes and 
the deletion of five analytes. See section II of this final rule. 
Additional analytes can be found in section II.B.1. of this final rule, 
Table 1, and deleted analytes are listed in section II.B.6 of this 
final rule.
     We are amending Sec. Sec.  493.923(b)(1), 493.927(c)(1), 
493.931(c)(1), 493.933(c)(1), 493.937(c)(1), 493.941(c)(1), and 
493.959(d)(1) to clarify that for the purpose of achieving consensus, 
PT programs must attempt to grade using both participant and referee 
laboratories before determining that the sample is ungradable.
 Section 493.927 (General Immunology)
    ++ We are correcting typographical or editorial errors in the 
proposed criteria for acceptable performance for alpha-1-antitrypsin, 
alpha-fetoprotein (tumor marker), complement C3, complement C4, 
antinuclear antibody, antistreptolysin O.
    ++ We are modifying the proposed AL for immunoglobulin A (IgA) of 
15 percent and finalizing the AL for IgA as 20 
percent based on public comments.
    ++ We are finalizing the proposed criteria for acceptable 
performance for antinuclear antibody, antistreptolysin O, rheumatoid 
factor, and rubella.
 Section 493.931 (Routine Chemistry)
    ++ We are finalizing the proposed ALs in the criteria for 
acceptable performance.
    ++ We are correcting the units for prostate specific antigen 
(total).
    ++ We are making a technical change to CK-MB isoenzymes to address 
measurement by electrophoresis or direct mass determination.
    ++ We are also modifying the proposed criteria for acceptable 
performance for hemoglobin A1c of 10 percent and finalizing 
the AL for hemoglobin A1c to 8 percent based on public 
comments.
 Section 493.933 (Endocrinology)
    ++ We are finalizing the proposed percentage based ALs in the 
criteria for acceptable performance.
 Section 493.937 (Toxicology)
    ++ We are finalizing the proposed concentration limits and 
percentage based ALs in the criteria for acceptable performance.
    ++ We are finalizing the proposed requirement that PT programs must 
provide samples that cover the full range of samples that could occur 
in patient specimens.
    ++ We are correcting the units for phenytoin and vancomycin.
 Section 493.941 (Hematology)
     We are finalizing the proposed AL for leukocyte count.
    ++ We are finalizing the proposed revision to units of reporting 
for prothrombin time to include seconds and INR (international 
normalized ratio) and that laboratories must report prothrombin time in 
the same was as they report patient results.
    ++ We are finalizing the proposed requirement that laboratories 
performing both cell counts and differentials must enroll and 
participate in PT for both.
    ++ We are finalizing the proposed change to the criteria for 
acceptable performance for ``cell identification'' from 90 percent to 
80 percent.
 Section 493.959 (Immunohematology)
    ++ We are finalizing the proposed change to the criteria for 
acceptable performance for unexpected antibody detection from 80 
percent to 100 percent.

[[Page 41218]]

IV. Collection of Information Requirements

    Under the Paperwork Reduction Act of 1995, we are required to 
provide 30-day notice in the Federal Register and solicit public 
comment before a collection of information requirement is submitted to 
the Office of Management and Budget (OMB) for review and approval. In 
order to fairly evaluate whether an information collection should be 
approved by OMB, section 3506(c)(2)(A) of the Paperwork Reduction Act 
of 1995 requires that we solicit comment on the following issues:
     The need for the information collection and its usefulness 
in carrying out the proper functions of our agency.
     The accuracy of our estimate of the information collection 
burden.
     The quality, utility, and clarity of the information to be 
collected.
     Recommendations to minimize the information collection 
burden on the affected public, including automated collection 
techniques.
    We are soliciting public comment on each of these issues for the 
following sections of this document that contain information collection 
requirements (ICRs).
    The requirements and burden will be submitted to OMB under (OMB 
control number 0938-New).

A. Clarification for Reporting of Microbiology Organism Identification

    We proposed to clarify a requirement at Sec. Sec.  493.801(b), 
493.911(b), 493.913(b), 493.915(b), 493.917(b), and 493.919(b), to 
emphasize the point that, as currently required, laboratories must 
report PT results for microbiology organism identification to the 
highest level that they report results on patient specimens. In 
accordance with the implementing regulations of the PRA at 5 CFR 
1320.3(b)(2), we believe the reporting of microbiology organism 
identification is a usual and customary practice when reporting PT 
results to PT programs. We are able to determine how many laboratories 
provide services in microbiology; however, we are unable to determine 
if the laboratories are enrolled in the appropriate PT outside of the 
survey process, or if the microbiology PT samples for which the 
laboratory is enrolled are required under subpart I. There are no data 
systems that capture this information. We estimate the number of 
laboratories that are not currently reporting microbiology organisms to 
the highest level that they report results on patient specimens to be 
about 10 percent of 34,113 laboratories which is 341 laboratories. We 
estimate it would take 20 minutes for a laboratory to fill this 
information on the PT submission form. Each laboratory would report 
this information 3 times per year and would take approximately 1 hour. 
The total annual burden is 341 hours (341 laboratories x 1 hour). A 
Clinical Laboratory Technologists/Technicians (29-2010) would perform 
this task at an hourly wage of $27.36 as published in 2021 by the 
Bureau of Labor Statistics.\11\ The wage rate would be $54.72 to 
include overhead and fringe benefits. The total cost would be $18,660 
(341 hours x $54.72).
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    \11\ https://www.bls.gov/oes/tables.htm.
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B. Optional On-Site Visits to PT Programs

    At Sec.  493.901(e), we proposed to add the requirement that HHS 
may require on-site visits for all initial PT program applications for 
HHS approval and periodically for previously HHS-approved PT programs 
either during the reapproval process or as necessary to review and 
verify the policies and procedures represented in its application and 
other information, including, but not limited to, review and 
examination of documents and interviews of staff. There is no 
collection of information requirements associated with this proposed 
requirement because the documentation is already being collected and 
maintained by the PT program as normal course of business and is a 
usual and customary practice in accordance with implementing 
regulations of the PRA at 5 CFR 1320.3(b)(2).

C. PT Program Reapproval

    At Sec.  493.901(f), we proposed to specify that we may require a 
PT program to reapply for approval using the process for initial 
applications if widespread or systemic problems are encountered during 
the reapproval process. If a PT program would need to reapply for 
approval using the initial application process, we would estimate that 
the cost would be 10 hours for document collection. The total burden is 
90 hours (9 PT programs x 10 hour). However, this would not be an 
annual burden, rather it would only occur under the circumstances 
outlined above, and we believe that these would only occur rarely. An 
Office/Administrative Support Worker (43-9199) would perform this task 
at an hourly wage of $20.47 as published in 2021 by the Bureau of Labor 
Statistics.\12\ The wage rate would be $40.94 to include overhead and 
fringe benefits. The total cost would be $3,685 (90 hours x $40.94).
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    \12\ https://www.bls.gov/oes/tables.htm.
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D. Withdrawal of Approval of a PT Program

    At Sec.  493.905, we proposed to add that HHS may withdraw the 
approval of a PT program at any point in the calendar year if the PT 
program provides false or misleading information that is necessary to 
meet a requirement for program approval or if the PT program has failed 
to correct issues identified by HHS related to PT program requirements. 
We also proposed to add a requirement that the PT program may request 
reconsideration. We believe this is excepted because of it being an 
administrative action per 5 CFR 1320.4(a)(2).

E. Submission of PT Data by Laboratories

    At Sec.  493.901(c)(6), we proposed to add the requirement that PT 
programs limit the participants' online submission of PT data to one 
submission or that a method be provided to track changes made to 
electronically reported results. As discussed in section II.C. of this 
final rule, based on public comments from PT programs and laboratories 
that this requirement would be burdensome and expensive, we are not 
finalizing this proposal.
    Table 2 reflects the total burden and associated costs for the 
provisions included in this final rule.

[[Page 41219]]

[GRAPHIC] [TIFF OMITTED] TR11JY22.001

V. Regulatory Impact Analysis

A. Statement of Need

    Proficiency testing (PT) has long been recognized as a critical 
component of a quality management system. It was first required at a 
national level for some clinical laboratories under CLIA `67. When CLIA 
`88 was enacted, and its implementing regulations were finalized in 
1992, all clinical laboratories that perform nonwaived testing became 
subject to the CLIA PT requirements. Since that time, there have been 
many changes in the practice of laboratory medicine and improvements in 
the analytical accuracy of test methods, such that HHS decided to 
assess the need to revise the PT regulations to ensure the accuracy and 
reliability of testing currently being used for clinical decision-
making and improved patient outcomes. For example, a number of analytes 
and tests now used for making clinical decisions were not recognized or 
commonly used at the time the CLIA PT requirements were published on 
February 28, 1992 at 42 CFR part 493 (57 FR 7002). Improvements in 
analytical accuracy required revisions to the criteria for acceptable 
performance to reflect the current practices and better assess clinical 
laboratory performance. We based our decision to update the regulations 
and incorporate the changes being finalized in this rule in part, as 
discussed above, upon advice from the Clinical Laboratory Improvement 
Advisory Committee (CLIAC), a Federal advisory committee charged with 
providing recommendations to HHS on revisions needed to CLIA. The 
members of CLIAC are knowledgeable about laboratory medicine and 
quality.

B. Overall Impact

    We have examined the impacts of this rule as required by Executive 
Order 12866 on Regulatory Planning and Review (September 30, 1993), 
Executive Order 13563 on Improving Regulation and Regulatory Review 
(January 18, 2011), the Regulatory Flexibility Act (RFA) (September 19, 
1980, Pub. L. 96-354), section 1102(b) of the Social Security Act, 
section 202 of the Unfunded Mandates Reform Act of 1995 (March 22, 
1995; Pub. L. 104-4), Executive Order 13132 on Federalism (August 4, 
1999) and the Congressional Review Act (5 U.S.C. 804(2)).
    Executive Orders 12866 and 13563 direct agencies to assess all 
costs and benefits of available regulatory alternatives and, if 
regulation is necessary, to select regulatory approaches that maximize 
net benefits (including potential economic, environmental, public 
health and safety effects, distributive impacts, and equity). Section 
3(f) of Executive Order 12866 defines a ``significant regulatory 
action'' as an action that is likely to result in a rule: (1) having an 
annual effect on the economy of $100 million or more in any one year, 
or adversely and materially affecting a sector of the economy, 
productivity, competition, jobs, the environment, public health or 
safety, or State, local or tribal governments or communities (also 
referred to as ``economically significant''); (2) creating a serious 
inconsistency or otherwise interfering with an action taken or planned 
by another agency; (3) materially altering the budgetary impacts of 
entitlement grants, user fees, or loan programs or the rights and 
obligations of recipients thereof; or (4) raising novel legal or policy 
issues arising out of legal mandates, the President's priorities, or 
the principles set forth in the Executive Order. A regulatory impact 
analysis (RIA) is required for economically significant regulatory 
actions that are likely to impose costs or benefits of $100 million or 
more in any given year. We prepared the RIA and found that this PT 
final rule does not meet the threshold of section 3(f)(1) of the 
Executive Order for a significant regulatory action. In addition, our 
upper limit of estimated impact is under the threshold of $165 million 
for the year of 2022 under the Unfunded Mandates Reform Act (UMRA). 
Nevertheless, we have voluntarily performed an RIA, as would be 
required for an economically significant regulation.
    This rule revises the CLIA PT requirements and affects 
approximately 35,967 clinical laboratories subject to participation in 
PT, resulting in some cost implications (Table 5). In addition, as a 
result of this final rule, the eight existing CLIA-approved PT programs 
will incur some costs as they modify their programs to meet the 
specified requirements. It will also have an effect on CLIA-exempt 
States regarding State PT requirements.
    The RFA requires agencies to analyze options for regulatory relief 
of small entities, if a rule has a significant impact on a substantial 
number of small entities. For purposes of the RFA, we assume that the 
great majority of clinical laboratories and PT programs are small 
entities, either by being nonprofit organizations or by meeting the 
Small Business Administration definition of a small business (having 
revenues of less than $8.0 million to $41.5 million in any 1 year). For 
purposes of the RFA, we believe that approximately 82 percent of 
clinical laboratories qualify as small entities based on their 
nonprofit status as reported in the American Hospital Association Fast 
Fact Sheet, updated January 2021 \13\ and 100 percent of PT programs 
are nonprofit organizations. Individuals and States are not included in 
the definition of a small entity. As its measure of significant 
economic impact on a substantial number of small entities, HHS uses a 
change in revenue of more than 3 to 5 percent. We do not believe that 
this threshold will be reached by the requirements in this final rule. 
Therefore, the Secretary has certified that this final rule will not 
have a significant economic impact on a substantial number of small 
entities. We have included several provisions in this rule to address 
the requirements of the RFA and provide regulatory relief or minimize 
burden for small entities such

[[Page 41220]]

as laboratories and PT programs. The first is incorporating a phase-in 
period for implementation of this rule. This phase-in will provide time 
for laboratories to identify PT programs offering the newly required PT 
and subscribe to PT for any of the analytes or tests that they offer. 
It will also provide the time needed by PT programs to add new analytes 
and tests to their programs, which requires the identification of new 
sources of PT materials and revision of administrative processes to 
accommodate the revised requirements. Other changes that will decrease 
burden, which are incorporated in this rule as a result of public 
comments from laboratories and PT programs, were several proposed 
revisions to microbiology PT. These proposed changes included adding PT 
requirements for susceptibility or resistance testing in the 
subspecialties of mycology and virology and adding a PT requirement for 
resistance testing in bacteriology. Because public comments indicated 
these requirements would be difficult to comply with due to limited 
materials and variability in the testing, we are not finalizing those 
changes in this rule, which mitigates burden that would have been 
placed on both laboratories and PT programs. In addition, because of 
similar public comments that questioned the value of currently required 
PT for susceptibility testing in mycobacteriology, we are removing this 
requirement in this final rule. These changes will provide regulatory 
flexibility and reduce burden to small entities.
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    \13\ https://www.aha.org/statistics/fast-facts-us-hospitals.
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    In addition, section 1102(b) of the Social Security Act requires us 
to prepare a regulatory impact analysis if a rule may have a 
significant impact on the operations of a substantial number of small 
rural hospitals. This analysis must conform to the provisions of 
section 604 of the RFA. For purposes of section 1102(b) of the Act, we 
define a small rural hospital as a hospital that is located outside of 
a metropolitan statistical area and has fewer than 100 beds. We do not 
expect this final rule will have a significant impact on small rural 
hospitals and we are unable to estimate the number of laboratories that 
support small rural hospitals. Such hospitals often provide limited 
laboratory services and may refer testing for the newly required 
analytes to larger hospitals. For the small rural hospitals with 
laboratories that perform testing for the new analytes, we expect they 
are already performing PT for other analytes and minimal effort will be 
required since they should already have PT policies and procedures in 
place. Therefore, the Secretary has certified that this final rule will 
not have a significant impact on the operations of a substantial number 
of small rural hospitals.
    Section 202 of the UMRA also requires that agencies assess 
anticipated costs and benefits before issuing any rule whose mandates 
require spending in any one year of $100 million in 1995 dollars, 
updated annually for inflation. In 2022, that threshold is 
approximately $158 million. This rule will not impose an unfunded 
mandate on States, tribal governments, or the private sector of more 
than $165 million annually and thus does not meet the UMRA threshold.
    Executive Order 13132 establishes certain requirements that an 
agency must meet when it promulgates a final rule that imposes 
substantial direct requirement costs on State and local governments, 
preempts State law, or otherwise has Federalism implications. The 
changes in this rule will not have a substantial direct effect on State 
and local governments, preempt State law, or otherwise have a 
Federalism implication and there is no change in the distribution of 
power and responsibilities among the various levels of government. This 
rule will not impose substantial direct compliance costs on State and 
local governments that are not required by statute. A significant 
number of laboratories affected by this rule are not operated by State 
or local governments. Therefore, promulgation of this rule will not 
cause substantial additional costs to State and local governments.

C. Anticipated Effects

    This final rule will impact approximately 35,967 clinical 
laboratories (total of Certificate of Compliance and Certificate of 
Accreditation laboratories, as of January 2020) required to participate 
in PT under the CLIA regulations implemented by the February 28, 1992 
final rule, eight current CLIA-approved PT programs, and to a lesser 
extent, in vitro diagnostics (IVD) manufacturers, healthcare providers, 
laboratory surveyors, and patients. Although complete data are not 
available to calculate all estimated costs and benefits that will 
result from the changes made in this rule, we are providing an analysis 
of the potential impact based on available information and certain 
assumptions. Implementation of these requirements will result in 
changes that will have both quantifiable and non-quantifiable impacts 
on laboratories, PT programs, and others mentioned above. In estimating 
the quantifiable impacts, we separated the laboratory specialties into 
two broad categories that include: (1) PT changes to the microbiology 
specialty; and (2) PT changes to non-microbiology specialties. This was 
done because the PT requirements differ for microbiology than for other 
laboratory specialties and laboratories that are certified to perform 
microbiology testing may be impacted differently than those that 
perform non-microbiology clinical testing. In each microbiology 
subspecialty, PT participation is required based on the types of 
services offered by a laboratory, and an overall score is given per 
that subspecialty, whereas in the other specialties and subspecialties, 
PT participation is required and scores are given based on specific 
required analytes listed in the regulations.
1. Quantifiable Costs for Laboratories
    CDC receives catalogs from all CLIA-approved PT programs annually. 
We estimated material costs for purchasing PT materials based on the 
range of 2020 catalog prices from the eight CLIA-approved PT programs. 
In estimating the labor costs for performing PT for all laboratory 
specialties that will be affected by this regulatory change, we assumed 
the average national clinical laboratory fee schedule \14\ as an 
estimate of the cost the laboratory incurs when testing each sample (or 
challenge). This amount represents the average reimbursement to 
laboratories performing patient testing for that analyte or test. We 
also assume the cost for testing patient samples is the same as the 
cost for testing PT samples.
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    \14\ CMS Clinical Laboratory Fee Schedule Files: https://www.cms.gov/Medicare/Medicare-Fee-for-Service-Payment/ClinicalLabFeeSched/Clinical-Laboratory-Fee-Schedule-Files.
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    We calculated that, on average, the cost impact would be between 
$695 and $2,511 per laboratory, with laboratories testing fewer 
analytes bearing a smaller burden.
a. Costs of PT Changes to the Microbiology Specialty
    Changes to the microbiology specialty include changes in each of 
the subspecialties (bacteriology, mycobacteriology, mycology, 
parasitology, and virology) that will replace the types of services 
offered and the examples of organisms to be included over time with a 
list of categories of tests and groups of microorganisms for which PT 
is required. In addition, this rule finalizes other changes in the CLIA 
regulations, Subpart I for each individual subspecialty. These changes 
will have a cost impact on laboratories. As stated in

[[Page 41221]]

CLIA at Sec.  493.801(a)(2)(ii) and Sec.  493.1236(c)(1), for tests or 
procedures performed by the laboratory that are not listed in Subpart 
I, Proficiency Testing Programs for Nonwaived Testing, a laboratory 
must verify the accuracy of that test or procedure at least twice 
annually. Although we do not have a way to estimate how many 
microbiology laboratories voluntarily enroll in PT to meet this 
requirement, we assume the added burden of performing the newly 
required PT would be minimal for those already performing voluntary PT. 
For the 5,341 affected microbiology laboratories, the estimated cost of 
the quantifiable changes to required PT for each microbiology 
subspecialty follows.
    To estimate the costs that will be incurred by laboratories to 
purchase PT materials to meet the revised requirements for the 
microbiology specialty, we compiled a range of PT material cost 
estimates per each challenge using 2020 catalog pricing for each PT 
program. For this analysis we refer to the PT catalog offerings as 
``modules.'' In microbiology, PT programs offer different types of 
modules. Individual modules such as stain(s), antigen detection, or 
toxin detection are intended for reporting a result for a single type 
of test. Many microbiology modules include challenges that address 
different types of testing. These modules, such as urine culture, may 
include individual PT challenges for Gram stain, bacterial 
identification, and antimicrobial susceptibility testing. In many 
cases, estimating the challenge cost was difficult because PT programs' 
pricing varies and in some cases the PT challenge cost per microbiology 
test depends upon whether the test is offered as an individual module 
or as part of a collection of multiple types of PT challenges in a 
module. In addition, to accurately estimate the challenge cost, we had 
to account for differences in the frequency at which the PT programs 
currently offer their modules and challenges. For example, one PT 
program may offer an antigen detection module at a frequency of two 
events per year, and three samples per event (six total samples per 
year), while another offers a similar module at three events per year, 
and five samples per event (15 total samples per year). Based upon the 
module type and frequency, we estimated the total low and high 
challenge cost for PT material using the range of 2020 catalog prices 
from the eight CLIA-approved PT programs for microbiology. Details are 
explained under each subsection. We acknowledge that these estimated 
ranges may be higher than the actual costs of requiring additional PT 
since laboratories may already voluntarily purchase PT to meet the 
biannual CLIA requirement for verifying the accuracy of testing. 
However, we do not have a way of estimating the number of laboratories 
or the cost of this voluntary participation.
    In estimating the number of microbiology laboratories that will be 
impacted by each of the regulatory changes, we determined the numbers 
of Certificate of Compliance (CoC) and Certificate of Accreditation 
(CoA) laboratories for each microbiology subspecialty using the CMS 
Quality Improvement and Evaluation System (QIES) database. To 
categorize the laboratories as described below, the QIES database was 
used to determine the accreditation organization for each CoA 
laboratory.
    We designated two laboratory categories when estimating the impact 
of the final PT rule in microbiology:
     Laboratories participating in a PT program for already 
required microbiology PT (Category M1).
     Laboratories not participating in a PT program for newly 
required microbiology PT (Category M2).
Category M1: Laboratories Already Participating in Required 
Microbiology PT
    For changes or additions to required microbiology PT, we used data 
from the PT program event summaries provided to CDC by the PT programs 
to estimate the total number of laboratories performing the already 
required PT. We then used that number to estimate how many laboratories 
would be affected by proposed changes or additions to the required PT.
Category M2: Laboratories Not Participating in a PT Program for Newly 
Required Microbiology PT
    We used Certificate of Accreditation data to estimate the number of 
laboratories that are subject to the microbiology PT requirements in 
this rule and are not already participating in a PT program. Of the 
seven CLIA-approved accreditation organizations, data were provided by 
COLA showing how many of the 6,999 COLA-accredited laboratories offer 
testing for the microbiology tests that are being added to the list for 
required PT. We used these data to estimate the percentage of COLA-
accredited laboratories that provide testing for these microbiology 
tests. We assumed that COLA-accredited laboratories are similar to 
Certificate of Compliance laboratories and laboratories accredited by 
deemed status organizations other than the College of American 
Pathologists (CAP) (who did not provide data) with regard to test 
volumes and the microbiology testing they provide. Therefore, we 
assumed that the percentage of COLA-accredited laboratories that 
perform a specific microbiology test could be used to approximate the 
total number of laboratories that perform the test. For the newly 
required microbiology PT, the number of CAP-accredited laboratories was 
considered negligible because they are already required to purchase PT 
for all testing performed and were not included in the total. We 
analyzed each proposed change for the microbiology specialty for each 
category and added our estimates to obtain the total projected impact 
on all affected laboratories.
(1) Costs of the PT Changes in the Bacteriology Subspecialty
    In the bacteriology subspecialty, the changes being finalized in 
this rule that may have a cost impact include the determination of 
bacterial morphology as part of the Gram stain module, the addition of 
bacterial toxin detection as required PT, and the addition of a second 
antimicrobial susceptibility testing challenge per year. Gram stain 
reaction is currently required in the PT regulations and all PT 
programs that offer a Gram stain PT module also offer the determination 
of bacterial morphology as part of the same module. We know the numbers 
of total laboratories enrolled in the PT program modules that require 
Gram stain reporting from the PT program event summaries. To determine 
the number of laboratories that will be impacted by this change, we 
calculated the number currently enrolled in Gram stain PT. Since this 
change will require that these laboratories report bacterial morphology 
in addition to Gram stain reaction on each challenge, we estimate the 
cost impact would be minimal. We estimated the range of costs by using 
the number of category M1 laboratories that perform Gram stain; the 
estimate of the cost the laboratory incurs when testing each challenge, 
using the average national CMS clinical laboratory fee schedule; the 
low price and high price per challenge for PT (based on PT program 
catalog variations); and the number of challenges required per year 
using one challenge for the low estimate (Table 3) and 15 challenges 
for the high estimate (Table 4).
    To evaluate the impact of requiring PT for bacterial toxin 
detection, we determined the total number of category M2 laboratories 
for bacteriology. Laboratories performing voluntary PT

[[Page 41222]]

for bacterial toxin detection are already meeting the new PT 
requirements. Since CAP-accredited laboratories are already required to 
perform PT if they perform bacterial toxin detection, we assumed they 
are already meeting the new PT requirements and did not include them in 
our estimate. The range of estimated costs was determined by using the 
number of category M2 impacted laboratories that perform bacterial 
toxin detection; the estimate of the cost the laboratory incurs when 
testing each challenge, using the average national CMS clinical 
laboratory fee schedule; the low price and high price per challenge for 
PT (based on PT program catalog variations); and the number of 
challenges required per year using one challenge for the low estimate 
(Table 1) and 15 challenges for the high estimate (Table 3).
    Currently, one sample or challenge per testing event is required 
for antimicrobial susceptibility testing in bacteriology. To evaluate 
the impact of increasing the required antimicrobial susceptibility 
testing from one challenge per year to two challenges per year, we 
calculated the total number of category M1 laboratories already 
participating in PT for antimicrobial susceptibility testing. The range 
of estimated costs was determined by using the number of category M1 
laboratories that currently perform antimicrobial susceptibility 
testing; the estimate of the cost the laboratory incurs when testing 
each challenge, using the average national CMS clinical laboratory fee 
schedule; the low price and high price per challenge for PT (based on 
PT program catalog variations); and the number of challenges required 
per year using one challenge for the low estimate (Table 3). 
Considering all of the potential cost impacts, the range of estimated 
impact for the proposed bacteriology subspecialty changes for the first 
year is $169,128 to $1,058,207.
(2) Costs of the PT Changes in the Mycobacteriology Subspecialty
    Changes to add a second antimycobacterial susceptibility or 
resistance testing challenge per event were proposed for the 
mycobacteriology subspecialty. However, as discussed in section III.E. 
of this final rule, due to public comments, those changes are not being 
finalized. In addition, due to the public comments received, the 
requirement for susceptibility testing in mycobacteriology is being 
removed altogether in this rule. Although there may be a cost savings 
for the small number of laboratories that perform antimycobacterial 
susceptibility testing, we are assuming that the majority of these 
laboratories will continue to subscribe to PT for this test to meet the 
requirement at Sec. Sec.  493.801(a)(2)(ii) and 493.1236(c)(1) to 
verify the accuracy of testing twice per year. As such, we are not 
anticipating a significant cost savings by removing this requirement 
and are not able to estimate the impact.
(3) Costs of the PT Changes in the Mycology Subspecialty
    In the mycology subspecialty, the changes being finalized in this 
rule that may have a cost impact include the addition of required PT 
for direct fungal antigen detection and detection of the presence or 
absence of fungi and aerobic actinomycetes without identification. To 
evaluate the impact of the required PT for direct fungal antigen 
detection, we determined the total number of category M2 laboratories 
for mycology. Laboratories performing voluntary PT for direct fungal 
antigen detection are already meeting the new PT requirements. Since 
CAP-accredited laboratories are already required to perform PT if they 
perform direct fungal antigen detection, we assumed they are already 
meeting the new PT requirements and did not include them in our 
estimate. The range of estimated costs was determined by using the 
number of category M2 impacted laboratories that perform direct fungal 
antigen detection; the estimate of the cost the laboratory incurs when 
testing each challenge, using the average national CMS clinical 
laboratory fee schedule; the low price and high price per challenge for 
PT (based on PT program catalog variations); and the number of 
challenges required per year using one challenge for the low estimate 
(Table 3) and 15 challenges for the high estimate (Table 4).
    The newly required detection of the presence or absence of fungi 
and aerobic actinomycetes without identification impacts laboratories 
that are currently performing dermatophyte identification using 
dermatophyte test medium to determine the presence or absence of 
dermatophytes in a patient specimen. We calculated the impact using the 
same methodology as was performed to determine the impact of the 
proposal to include direct fungal antigen detection (Tables 1 and 2). 
Considering the cost impact of this rule in the mycology subspecialty, 
the range estimated for the first year is $3,288 to $61,940.
(4) Costs of the PT Changes in the Parasitology Subspecialty
    In the parasitology subspecialty, the change being finalized in 
this rule that may have a cost impact is the addition of required PT 
for direct parasite antigen detection. To evaluate the potential impact 
of this addition, we determined the total number of category M2 
laboratories for parasitology. Laboratories performing voluntary PT for 
direct parasite antigen detection are already meeting the new PT 
requirement. Since CAP-accredited laboratories are already required to 
perform PT if they perform direct parasite antigen detection, we 
assumed they are already meeting the new PT requirement and did not 
include them in our estimate. The range of estimated costs was 
determined by using the number of category M2 impacted laboratories 
that perform direct parasite antigen detection; the estimate of the 
cost the laboratory incurs when testing each challenge, using the 
average national CMS clinical laboratory fee schedule; the low price 
and high price per challenge for PT (based on PT program catalog 
variations); and the number of challenges required per year using one 
challenge for the low estimate (Table 3) and 15 challenges for the high 
estimate (Table 4). Considering the potential cost impact of this rule 
in the parasitology subspecialty, the range estimated for the first 
year is $8,098 to $458,136.
(5) Costs of the PT Changes in the Virology Subspecialty
    In the virology subspecialty, the proposed change that would have 
had a cost impact was the addition of two antiviral susceptibility or 
resistance testing challenges per year. However, as a result of the 
public comments received, that change is not being finalized in this 
rule. Therefore, we do not estimate a cost impact resulting from this 
rule in the subspecialty of virology.
BILLING CODE 4120-01-P

[[Page 41223]]

[GRAPHIC] [TIFF OMITTED] TR11JY22.002

[GRAPHIC] [TIFF OMITTED] TR11JY22.003


[[Page 41224]]


BILLING CODE 4120-01-C
b. Costs of PT Changes to the Non-Microbiology Specialties/
Subspecialties
    The changes being finalized in this rule in specialties and 
subspecialties other than microbiology include adding 30 new analytes 
at the frequency of three events per year and five challenges per 
event. According to CLIA, laboratories with Certificates of Compliance 
and Certificates of Accreditation are required to perform PT. There are 
35,967 clinical laboratories that will be affected (18,938 Certificate 
of Compliance and 17,029 Certificate of Accreditation laboratories). 
The changes to required PT will be a new burden for some laboratories, 
but many laboratories are already paying for PT of these analytes. As 
previously mentioned, in CLIA Sec. Sec.  493.801(a)(2)(ii) and 
493.1236(c)(1), for tests or procedures performed by the laboratory 
that are not listed in the CLIA regulations Subpart I, the laboratory 
must verify the accuracy of that test or procedure at least twice 
annually. Since laboratories may voluntarily enroll in PT as one way to 
meet this requirement, we assume the added burden would be minimal. We 
have evidence from laboratories that responded to our national PT 
survey that of those who were not already required by the CAP to 
perform PT on more than the CLIA-required analytes, 39 percent 
purchased PT for 1 to 5 analytes, 17 percent for 6 to 10 analytes, 10 
percent for 11 to 20 analytes, and 10 percent for more than 20 
analytes. We estimated the costs for newly required analytes by 
grouping all affected laboratories into four categories: (1) CAP 
enrolled in CAP PT program, (2) CAP enrolled in 7 non-CAP PT Program, 
(3) Non-CAP not enrolled in 7 non-CAP PT program, and (4) Non-CAP 
enrolled in 7 non-CAP PT program), calculating the number of 
laboratories in each category and calculating the costs using the 
analyte price, test reimbursement rate and labor cost to update PT 
policies and procedures. We also tightened ALs and added concentration 
limits for several currently required analytes, which may have an 
impact on laboratories, but the cost impact is not included in our 
estimate. In addition, with this rule, we are finalizing the removal of 
five required analytes (ethosuximide, LDH isoenzymes, primidone, 
procainamide/NAPA, and quinidine) that are infrequently performed. As 
such, we do not anticipate this being a substantial cost savings since 
laboratories may continue to use PT voluntarily as a way of meeting the 
biannual accuracy verification requirement.
    Three issues had to be considered to estimate the costs for PT 
materials for new analytes: PT programs may offer analytes as an 
individual analyte or as part of a module that combines multiple 
analytes; some of the new analytes may already be offered but at a 
frequency other than the CLIA-required frequency (3 x 5 = 15 samples 
per year); and the extent to which laboratories already use PT varies 
that is, laboratories accredited by the CAP are required to enroll in 
PT for each test they perform. For all these reasons, laboratories 
enrolled in different PT programs will be impacted differently. Based 
on this observation and our inability to make estimates at the level of 
individual laboratories, we accounted for each of these variations when 
calculating the costs incurred.
    To account for the different prices each PT program charges for 
different analytes, as an individual analyte or as part of a module, we 
used a range of estimates based upon the PT programs' unit costs for PT 
currently offered. We used two approaches to estimate the cost of 
individual PT analytes. If the analyte was offered individually by the 
PT program, we used that price. However, if the analyte was not offered 
individually, we divided the panel price by the total number of 
analytes in the panel to determine the cost per analyte, which is used 
as individual analyte price. For the lower cost estimate, we selected 
the lowest individual analyte price among all PT providers. For the 
higher cost estimate, we used the highest individual analyte price. In 
some cases, PT programs offer PT for the new analytes at different 
frequencies, that is, different numbers of events per year and 
different numbers of challenges per event. Therefore, to accurately 
estimate future costs, we had to calculate the increased frequency for 
each analyte in order to achieve three events/year with five challenges 
per event.
    Implementation of this final rule will have different impacts on 
different laboratories mainly because laboratories either have a 
Certificate of Compliance or a Certificate of Accreditation and may be 
accredited by different accreditation organizations and purchase PT 
from different PT programs. Our analysis starts with CAP-accredited 
laboratories as CAP is not only a large accreditation organization but 
also the largest PT program. In estimating the number of affected 
laboratories as a result of this final rule, we acknowledged that any 
CAP-accredited laboratory that offers patient testing for one of the 
CAP PT program analytes must enroll in the relevant program for that 
analyte. However, CAP-accredited laboratories are permitted to enroll 
in PT from other CAP-approved PT programs. Laboratories not accredited 
by the CAP may purchase PT materials from any CLIA-approved PT program, 
including the CAP PT program. Therefore, we have designated four 
categories to estimate the cost impact of this rule.
Category 1: Laboratories Accredited by the CAP That Purchase Material 
From the CAP PT Program
    The CAP provided us with the number of CAP-accredited laboratories 
that are enrolled in their PT program for each new analyte.
    The cost increase was calculated on a per analyte basis by 
multiplying the cost per sample (PT material + CMS reimbursement 
amount) by the increase in frequency of samples and the number of 
laboratories that purchase PT from the CAP PT program. We estimate the 
costs for laboratories accredited by CAP that purchase material from 
the CAP PT program to be $4,498,535.
Category 2: CAP-Accredited Laboratories That Purchase PT Materials From 
Other PT Programs
    For the analytes we are adding in this rule, CAP-accredited 
laboratories are required to enroll in a CLIA-approved PT program. 
Ordinarily CAP-accredited laboratories enroll in the CAP PT program but 
are permitted to enroll in PT from other CAP-approved PT programs. 
Using the data the CAP provided, we calculated the total number of CAP-
accredited laboratories enrolled in one of the other PT programs 
provided through PT Program A, PT Program D, PT Program E, or PT 
Program G.
    The cost increase in this category was calculated on a per analyte 
basis. We were able to obtain the enrollment distribution of the CAP-
accredited laboratories in each of the non-CAP PT programs. The cost 
increase was calculated on a per analyte basis by multiplying the cost 
per sample (PT material + CMS reimbursement amount) by the increase in 
frequency of samples and the number of laboratories that purchase PT 
from the non-CAP PT program. We estimate the costs for CAP-accredited 
laboratories that purchase PT materials from other PT programs will 
range from $0 to $1,304,343.
Category 3: Laboratories Not Accredited by CAP That Are Not Already 
Enrolled in Other PT Programs
    To derive the minimum and maximum number of laboratories not 
already enrolled in a PT program that may provide testing for the newly 
required analytes, we began by

[[Page 41225]]

estimating that there are 22,119 laboratories that perform nonwaived 
testing and are not accredited by the CAP in the US. To facilitate the 
calculations, we presumed that laboratories not accredited by CAP will 
not purchase CAP PT. From the QIES database, we derived the number of 
laboratories not accredited by CAP that provide testing in each 
specialty and reasoned that this was the maximum number of laboratories 
not accredited by the CAP that might provide testing for each analyte.
    COLA provided us with the percentages of the approximately 6,999 
COLA-accredited laboratories that perform testing for each new analyte. 
We determined that COLA-accredited laboratories are similar to CoC 
laboratories in terms of their annual test volumes. Therefore, we 
assumed that the percentage of COLA-accredited laboratories that test 
each new analyte could be used to estimate the minimum number of CoC 
and CoA (other than CAP- or COLA-accredited) laboratories that test 
each analyte.
    We used the percentage of CAP-accredited laboratories that 
participate in PT for each new analyte to estimate the maximum number 
of CoC and CoA (other than CAP and COLA) laboratories that test each 
analyte. This percentage was much higher for many of the analytes when 
compared to the laboratories accredited by organizations other than the 
CAP. Since CAP-accredited laboratories are often either hospital-based 
or commercial laboratories that already participate in PT for the 
additional analytes, approximations for high estimates may 
substantially overestimate the number of laboratories impacted.
    Using the above information, we calculated low and high estimates 
for the total number of CoC and non-CAP-accredited CoA laboratories 
that may provide testing for each new analyte.
    For each new analyte, we calculated the number of CAP-accredited 
laboratories that buy from non-CAP PT programs by subtracting the CAP-
accredited laboratories enrolled in CAP PT from the total number of 
CAP-accredited laboratories.
    We derived a low estimate of the total number of laboratories not 
accredited by CAP and not enrolled in one of the non-CAP PT programs 
for each analyte. Negative estimates were taken as ``0.'' This 
represents our low estimate of the number of laboratories that will 
need to purchase PT for each analyte.
    To obtain the high estimate for the number of laboratories not 
accredited by CAP and not enrolled in one of the non-CAP PT programs, 
we took the high estimate of CoC laboratories and CoA laboratories not 
accredited by the CAP and subtracted the number of this subset of CoA 
laboratories already known to be enrolled in PT. For the high estimate 
of the number of laboratories not accredited by CAP and not enrolled in 
one of the non-CAP PT programs, we also used an additional criterion of 
the number of laboratories in the respective specialty from QIES to cap 
the estimate at the number of laboratories in the specialty. If this 
number was less than the high estimate of CoC laboratories and CoA 
laboratories accredited by a program other than CAP, then the high 
estimate was calculated by subtracting the number of laboratories not 
accredited by CAP and not enrolled in one of the non-CAP PT programs 
from the total number of laboratories in the specialty.
    The cost increase in this category was calculated on a per analyte 
basis. The minimum cost per sample that was the lowest across all seven 
non-CAP PT programs and the maximum cost per sample that was the 
highest across all seven non-CAP PT programs were used for these 
calculations. The minimum cost increase was calculated by multiplying 
the minimum cost per sample, including the CMS reimbursement amount, by 
the number of laboratories that are not purchasing PT from any PT 
program. The same calculation was made using the maximum cost per 
sample for the maximum cost increase. We estimate the costs for 
laboratories not accredited by CAP and not already enrolled in other PT 
programs will range from $7,047,880 to $58,710,510.
Category 4: Laboratories Not Accredited by the CAP and Enrolled in PT 
Programs Other Than the CAP PT Program
    We obtained the number of laboratories enrolled in PT programs 
other than the CAP PT program from the PT event summaries from each PT 
program. The cost increase in this category was calculated on a per 
analyte basis. The estimated cost increases were calculated for each of 
the non-CAP PT programs for which information was available. The 
minimum increase was calculated for each of the PT programs by 
multiplying the cost per sample, including the CMS reimbursement 
amount, by the increase in frequency of samples and the number of 
laboratories that purchase PT from that individual program. To 
determine the maximum increase, the same calculation was made using the 
highest cost per analyte, including the CMS reimbursement amount. We 
estimate the costs for laboratories not accredited by CAP and already 
enrolled in non-CAP PT programs will be $1,051,614.
c. Costs for Laboratories, Deemed Accreditation Organizations, Exempt 
States, and PT Programs To Update Policies and Procedures
    We expect that the 35,967 CoC and CoA laboratories will incur costs 
for the time needed to review the revised PT regulations and update 
their policies, procedures, and information technology (IT) systems, as 
needed, to be in compliance with the updated regulations. We assume a 
one-time burden of 4 to 8 hours per laboratory will be needed for this. 
A general management level employee (13-1111) would perform this task 
at an hourly wage of $46.91 per hour as published in 2020 by the Bureau 
of Labor Statistics (https://www.bls.gov/oes/current/oes_nat.htm). The 
wage rate would be $93.82 to include overhead and fringe benefits. 
Therefore, we estimate the one-time costs for CoC and CoA laboratories 
will range from $13,497,696 to $26,995,392 ($93.82 x 35,967 x 4 or 8 
hours). Similarly, seven approved accreditation organizations and two 
exempt States will need to review the regulations and may need to 
revise their survey policies and procedures to be consistent with the 
updated requirements. We estimate a one-time burden of 10 to 15 hours 
to review the revised regulations and to develop policies and 
procedures needed to reflect the new PT requirements. We assume the 
person performing this review will be a business management level 
employee (11-1021) paid $60.45 per hour as published in 2020 by the 
Bureau of Labor Statistics (https://www.bls.gov/oes/current/oes_nat.htm). The wage rate would be $120.90 to include overhead and 
fringe benefits. Therefore, we estimate the one-time costs for 
accreditation organizations and exempt States to update their policies 
and procedures will range from $10,881 to $16,322. For PT programs, we 
estimate a one-time burden of 30 to 35 hours for them to review the 
updated regulations, revise their policies and procedures, and add new 
analytes or microbiology tests that they choose to offer. We assume the 
person performing this job will be a business management level employee 
paid $60.45 per hour as published in 2020 by the Bureau of Labor 
Statistics (https://www.bls.gov/oes/current/oes_nat.htm). The wage rate 
would be $120.90 to include overhead and fringe benefits. Therefore, we 
estimate the one-time costs for PT programs will range from $36,270 to 
$42,315.

[[Page 41226]]

d. Results
    We estimate that the overall impact of adding requirements for the 
new analytes in the specialties and subspecialties other than 
microbiology will range from approximately $13 to $66 million for the 
first year (Table 5). Because of the larger number of non-CAP 
accredited laboratories, and the fact that they tend not to enroll in 
non-required PT as frequently as CAP-accredited laboratories do, we 
estimate that non-CAP accredited laboratories that are not enrolled in 
any PT program will have an impact between $7 and $59 million for the 
first year. We also estimate that laboratories not accredited by CAP 
that are enrolled in PT programs other than CAP will have a relatively 
minor impact, $1 million for the first year (Table 5).
BILLING CODE 4120-01-P
[GRAPHIC] [TIFF OMITTED] TR11JY22.004

    Table 6 shows the total estimated range of annual cost for the 
changes (including both microbiology and non-microbiology) in 
undiscounted 2020 dollars and discounted at 3 percent and 7 percent to 
translate expected costs in any given future years into present value 
terms. The base year is 2020 for the calculations displayed in Table 6 
and we assume costs in future years to be the same as costs in the base 
year.

[[Page 41227]]

[GRAPHIC] [TIFF OMITTED] TR11JY22.005


[[Page 41228]]


BILLING CODE 4120-01-C
d. Non-Quantifiable Costs
    A number of non-quantifiable cost impacts will also result for PT 
programs and laboratories when this rule becomes effective.
    As with any required PT, implementation of this final regulation 
does not require approved PT programs to offer additional analytes. 
Several programs already offer the analytes or tests that will be 
required, and, in these cases, we expect there to be a minimal cost 
impact on the PT programs. We expect there will initially be some 
increased expenditures for PT programs to implement the changes, even 
if they are only scaling up currently offered PT. We have included an 
estimate of those costs in this RIA. At the same time, PT programs will 
also increase revenue received if they increase the PT analytes or 
tests they offer. We have no way to estimate how many programs may 
choose to offer additional PT analytes or tests, but we assume that 
most will implement the changes included in the final rule. For some 
programs, this will mean offering an analyte or test for the first 
time, while for others it will mean increasing the yearly number of 
events and/or challenges per event. The costs will be relatively less 
for the programs that are already offering the PT analytes or tests, 
including those currently offering challenges at less than the PT 
frequency required under CLIA. There are also differences in what the 
PT programs charge laboratories for PT. In part, these differences 
depend upon the total number of samples distributed per year and how 
the PT is packaged; some PT is sold as modules that group several 
related analytes together. Because CLIA-approved PT programs are 
required to maintain non-profit status, any increased revenue that 
results from an expanded PT menu will not be turned into profit. We 
have attempted to account for the quantifiable impacts in our estimates 
for laboratories.
    When this rule becomes effective, some PT programs may cease 
offering the analytes that are no longer required, others may continue 
to offer them at a frequency less than that required under CLIA, and 
still others may continue to offer them at the PT frequency required 
under CLIA. For these reasons we are unable to estimate the cost impact 
to PT programs for this change.
    Although we cannot precisely predict how the changes may 
qualitatively affect clinical laboratories, we do not expect there to 
be major changes in how they function. We have quantified the costs we 
expect laboratories to incur but there may be costs associated with 
other administrative functions related to PT ordering, result 
reporting, and record keeping that we are not able to estimate. For 
those laboratories that currently purchase PT for the five analytes for 
which PT is no longer required, we cannot estimate the lowered 
expenditure for laboratories that stop buying PT materials and must 
begin doing something else to verify accuracy. Based on our focus 
groups and surveys, we know there are a variety of things laboratories 
may do to externally verify accuracy, ranging from splitting samples 
with other laboratories to purchasing PT materials voluntarily. Also, 
we do not know the extent to which split samples are tested, or how 
many patient samples might be tested in this way; there is no stated 
minimum number of specimens that must be tested semi-annually to verify 
accuracy. Therefore, we have not attempted to estimate the costs for 
alternative approaches that may be adopted to verify accuracy for the 
deleted analytes. Regardless of how laboratories might be impacted, we 
expect that they will not spend more than what they currently spend on 
PT for the analytes deleted, but we cannot estimate this. By not 
attempting to estimate the number of laboratories that may stop buying 
PT material for the deleted analytes, we may be slightly overestimating 
the net impact.
e. Benefits
    While we cannot quantify the benefits that implementation of this 
final rule revising the PT requirements will bring, we believe that the 
changes will improve the accuracy and reliability of testing and allow 
for quicker identification of unacceptable practice in laboratories, 
especially those laboratories that have not previously participated in 
PT. Remediation after identification of problems should also occur more 
quickly and clinical test results of marginal or inferior quality are 
less likely to be used as analytical systems will improve. All of these 
things will serve to minimize the potential adverse impact to patients 
and will benefit physicians and healthcare providers while not 
impacting access to testing.
    PT performance partially reflects daily clinical laboratory 
performance. Updating ALs will benefit laboratories by helping to 
ensure the accuracy and reliability of testing and providing a 
mechanism for laboratories to be held accountable for clinically 
appropriate patient test results, which directly affects the public's 
health. Both clinical laboratories and patients can benefit from 
continued monitoring of PT to help assess the success of intervention 
efforts to improve the overall quality of clinical laboratory testing.
    Another benefit that may result from adding new PT analytes and 
tests and updating the limits for acceptable PT performance under CLIA 
includes the generation of additional information on test performance 
and sources of errors that PT programs can share with laboratories. 
Such information can also be used as a source of training and can help 
to maintain the competency of testing personnel (Garcia, et al, 2014).
    Last, while we do not anticipate that the changes in this final 
rule will result in any costs on the IVD industry, we expect the IVD 
industry to potentially benefit by the changes made in this rule, from 
having the ability to track PT results for the added analytes to enable 
better and faster detection of problems with product manufacturing, 
including reagent problems. We are aware that some IVD manufacturers 
enroll in PT and are able to track the performance of the peer groups 
using their instruments in summary reports issued by the PT programs.
    Ultimately, we believe that laboratories, healthcare providers, 
patients, and the IVD industry will benefit from improved analytical 
performance \5\ that is expected to occur when this final rule becomes 
effective with this new rule.

D. Alternatives Considered

    A number of alternatives were considered in finalizing the changes 
in this rule. We considered the possibility of changing either the 
required frequency of PT events per year or changing the number of 
required PT challenges per event. Responses from our national survey 
did not support changing either parameter nor did CLIAC recommend any 
changes to the required PT frequency or number of challenges per event. 
Similarly, public comments received in response to the proposed rule 
did not suggest changes to required PT frequency or number of 
challenges per event. We did not perceive a benefit from either 
reducing or increasing the number of events per year. Reducing the 
number of events to two per year and keeping all other factors the same 
would cost less, but it would delay the potential time it takes to 
identify a poor performing laboratory as ``unsuccessful'' to at least 
12 months, instead of the current 8 months. Increasing the number of 
events might help to identify a laboratory with testing issues slightly 
earlier, but increasing the number of events would increase costs. In 
this final rule, we will continue to require five challenges per event, 
with a successful event score defined under

[[Page 41229]]

CLIA `88 as a minimum of four out of five challenges (80 percent) 
falling within the criteria for acceptable performance.
    For the microbiology specialty, we considered the possibility of 
including required PT analytes in each subspecialty at a frequency of 
three events per year with five challenges per event. We determined 
that the increase in required PT would result in an additional cost 
impact of more than five million dollars to laboratories who would be 
required to perform susceptibility testing for 15 challenges per year. 
For the non-microbiology specialties and subspecialties, we could have 
opted not to add any new PT analytes but testing of the analytes we are 
now adding in this rule is widespread and is important in clinical 
decision-making and public health testing. We also considered adding 
all analytes for which there was at least one existing PT program, but 
this alternative would have been excessively burdensome as it would 
mean adding hundreds of new required analytes which may not be 
necessary to identify problematic laboratory performance. We could have 
left the ALs as they were established in CLIA `88, but we rejected this 
approach as outdated given advancements in technology. We considered 
the option of enforcing the definition of peer group established in 
CLIA `88, but we decided this would be too expensive and ultimately 
unworkable because it would require PT programs to perform 
commutability testing using analyzers from multiple peer groups every 
time a new batch of PT materials was created.

E. Accounting Statement and Table

    We have prepared the following accounting statement showing the 
classification of expenditures associated with the provisions of this 
rule.
BILLING CODE 4120-01-P

[[Page 41230]]

[GRAPHIC] [TIFF OMITTED] TR11JY22.006


[[Page 41231]]


BILLING CODE 4120-01-C

F. Conclusion

    We estimate that the total cost for laboratories to participate in 
PT for the analytes and tests in this rule will be between $26 and $94 
million in 2020 dollars. Although the effect of the changes will 
increase costs, implementation of these changes in this final rule will 
increase the confidence of laboratory professionals and the end-users 
of test results, including physicians and other healthcare providers, 
patients, and the public, in the reliability and accuracy of test 
results.
    We have determined that this rule will not have a significant 
economic impact on a substantial number of small entities or a 
significant impact in the operations of a substantial number of small 
rural hospitals and for these reasons, we are not preparing analyses 
for either the RFA or section 1102(b) of the Act. However, we described 
actions being taken in finalizing this rule to reduce burden and 
minimize the impact on small entities such as laboratories and PT 
programs.
    In accordance with the provisions of Executive Order 12866, this 
regulation was reviewed by the Office of Management and Budget.

VI. Analysis of and Responses to Public Comments on the Paperwork 
Reduction and Regulatory Impact Analysis

    We have provided an analysis of the potential impact of this final 
rule, based upon available information and certain assumptions. We have 
prepared the Paperwork Reduction Act and the Regulatory Impact Analysis 
representing the costs and benefits of the final rule based on analysis 
of identified variables and data sources needed for this change. We 
requested that commenters provide any additional data that would assist 
us in the analysis of the potential impact of this regulation on CLIA-
certified laboratories, but we did not receive any additional data.
    Therefore, based on our analysis and assessment of the overall 
annual costs to the laboratories affected by this final rule, we are 
finalizing the provisions in this rule. The comments and our responses 
are set forth below:
    Comment: As part of regulatory impact analysis for the proposed 
rule, we described the benefits of PT and the need to update the 
regulations. Commenters representing accreditation organizations and 
laboratory professional organizations were supportive of the proposed 
changes, especially the expansion of the list of required PT analytes. 
The commenters noted that PT is a valuable quality indicator and 
measure of laboratory performance and they emphasized that the accuracy 
and reliability of laboratory testing is critical to patient safety and 
the delivery of quality healthcare services. A few commenters stated 
that PT is burdensome and expensive, one of them adding that the 
benefits of PT in reducing testing errors has not been documented 
through studies or other evidence.
    Response: We appreciate the comments that expressed support for the 
changes in the proposed rule and recognized the value of PT as a 
measure of laboratory quality and a mechanism to detect and prevent 
errors that can affect patient safety. However, we agree with the 
commenters who stated that it is difficult to quantify the value of PT 
and we recognize the financial and other resource costs associated with 
performing PT. Based on the positive comments received and previously 
published studies (7-10), we believe that PT is a useful adjunct to 
identify poor-performing laboratories and to help laboratories ensure 
the quality of their testing which directly affects patients, and 
ultimately the public's health.
    Comment: We received comments from accreditation organizations, 
professional organizations, businesses, and individuals concerning our 
estimate of the impact of the proposed rule. Several commenters stated 
that we had underestimated the overall impact, including the impact on 
individual laboratories and accreditation organizations, especially the 
administrative burden of new PT. While one commenter stated our 
methodology was correct, others disagreed, and one commenter stated 
that we failed to consider bigger changes to the way PT is conducted 
which could reduce costs. A few commenters suggested that we conduct a 
more comprehensive impact analysis.
    Response: We acknowledge that our analysis was limited by the 
availability of data and our ability to estimate all aspects of the 
proposed changes. In the proposed rule, we solicited comments and data 
to facilitate the determination of quantifiable estimates of the impact 
in the final rule. We did not receive any suggestions of alternative 
methods or data on which to base our estimates. Therefore, in this 
final rule we have used similar methodology to that used in the 
proposed rule with exceptions as follows. We added a range of estimates 
to cover the one-time costs that would be expected for CoC and CoA 
laboratories subject to PT to review the updated regulations; modify 
policies, procedures, and IT systems as needed; and enroll in 
appropriate PT to be in compliance with the revised requirements. We 
also modified the impact analysis to include estimation of the one-time 
costs for the seven deemed accreditation organizations and two exempt 
States to review the updated regulations and revise their survey 
policies and procedures to be consistent with the new PT requirements. 
Lastly, we added similar one-time estimates for PT programs to review 
the updated regulations, modify policies and procedures, and determine 
if they will choose to offer the new analytes or microbiology PT. We 
recognize that there will be ongoing costs for laboratories, deemed 
accreditation organizations, exempt States, and PT programs based on 
the revised list of required analytes and changes to microbiology PT. 
However, we are unable to project these costs since, although we do not 
know the number, some laboratories are already participating in PT for 
the new analytes and microbiology tests as a way of meeting the 
requirement to verify the accuracy of testing twice per year. For these 
laboratories, the ongoing additional costs may be minimal. Similarly, 
the accreditation organizations and exempt States may already be 
reviewing voluntary PT data for some of the newly required analytes and 
tests. With respect to ongoing costs for PT programs, we are also 
unable to estimate the costs. As previously described in this rule 
regarding the criteria used to select new analytes and microbiology PT, 
we are aware that at least three programs already offer PT for these 
analytes and tests, and we are unsure how many additional programs will 
choose to offer them since they are not required by CLIA to do so. For 
those that already offer the additional PT, we expect the ongoing costs 
to be minimal.
    Comment: Several commenters recommended that the effects of the 
recent Protecting Access to Medicare Act of 2014 (PAMA) regulations 
should be considered as part of the regulatory impact analysis in light 
of PAMA's impact on laboratory testing reimbursement under Medicare.
    Response: We recognize the impact of PAMA on Medicare payment for 
laboratory testing. However, PAMA was implemented in 2018 and those 
changes were independent of the CLIA PT changes that are now being 
finalized. We do not have data that would allow us to determine the 
cumulative effects of the two rules that were implemented at two 
separate points in time. We did use the CMS CLFS for 2020, which 
included post-PAMA payment rates, as

[[Page 41232]]

one part of our estimate of the costs of performing PT, as no other 
data sources were suggested by commenters.
    Comment: A commenter noted that the RIA had not accounted for the 
costs of disallowing the use of for-profit entities by PT programs for 
conducting any part of their business and suggested that the final rule 
should include this economic assessment.
    Response: The proposed rule did not specify that for-profit 
entities were disallowed for use by PT programs for conducting any part 
of their business. In this final rule, we are clarifying that the 
provision being finalized at Sec.  493.901(c)(8), previously proposed 
at Sec.  493.901(c)(9), requires that technical and scientific 
responsibilities, such as grading PT, must be carried out by nonprofit 
organizations, Federal or State agencies, or entities acting as a 
designated Federal or State agency. This is an inherent function of an 
approved PT program and should not result in additional costs for the 
programs. Contractors used to perform tasks such as manufacturing or 
transportation of samples are not required to be non-profit entities.
    Chiquita Brooks-LaSure, Administrator of the Centers for Medicare & 
Medicaid Services, approved this document on June 21, 2022.
    Rochelle P. Walensky, MD, MPH, Director of the Centers for Disease 
Control and Prevention, approved this document on June 17, 2022.

List of Subjects in 42 CFR Part 493

    Administrative practice and procedure, Grant programs-health, 
Health facilities, Laboratories, Medicaid, Medicare, Penalties, 
Reporting and recordkeeping requirements.
    For the reasons set forth in the preamble, the Centers for Medicare 
& Medicaid Services amends 42 CFR part 493 as set forth below:

PART 493--LABORATORY REQUIREMENTS

0
1. The authority citation for part 493 continues to read as follows:

    Authority: 42 U.S.C. 263a, 1302, 1395x(e), the sentence 
following 1395x(s)(11) through 1395x(s)(16).


0
2. Amend Sec.  493.2 by--
0
a. Adding the definitions of ``Acceptance limit'' and ``Peer group'' in 
alphabetical order; and
0
b. Revising the definition of ``Target value''.
    The additions and revision read as follows:


Sec.  493.2  Definitions.

* * * * *
    Acceptance limit means the symmetrical tolerance (plus and minus) 
around the target value.
* * * * *
    Peer group means a group of laboratories whose testing process 
utilizes similar instruments, methodologies, and/or reagent systems and 
is not to be assigned using the reagent lot number level.
* * * * *
    Target value for quantitative tests means:
    (1) If the peer group consists of 10 participants or greater:
    (i) The mean of all participant responses after removal of outliers 
(that is, those responses greater than three standard deviations from 
the original mean, as applicable);
    (ii) The mean established by a definitive method or reference 
methods; or
    (iii) If a definitive method or reference methods are not 
available, the mean of a peer group; or
    (2) If the peer group consists of fewer than 10 participants, the 
mean of all participant responses after removal of outliers (as defined 
in paragraph (1) of this definition) unless acceptable scientific 
reasons are available to indicate that such an evaluation is not 
appropriate.
* * * * *

0
3. Amend Sec.  493.20 by revising paragraph (c) to read as follows:


Sec.  493.20  Laboratories performing tests of moderate complexity.

* * * * *
    (c) If the laboratory also performs waived tests, compliance with 
Sec.  493.801(a) and (b)(7) and subparts J, K, and M of this part is 
not applicable to the waived tests. However, the laboratory must comply 
with the requirements in Sec. Sec.  493.15(e), 493.801(b)(1) through 
(6), 493.1771, 493.1773, and 493.1775

0
4. Amend Sec.  493.25 by revising paragraph (d) to read as follows:


Sec.  493.25  Laboratories performing tests of high complexity.

* * * * *
    (d) If the laboratory also performs waived tests, compliance with 
Sec. Sec.  493.801(a) and 493.801(b)(7) and subparts J, K, and M of 
this part are not applicable to the waived tests. However, the 
laboratory must comply with the requirements in Sec. Sec.  493.15(e), 
493.801(b)(1) through (6), 493.1771, 493.1773, and 493.1775.

0
5. Amend Sec.  493.801 by--
0
a. Redesignating paragraphs (b)(3) through (6) as paragraphs (b)(4) 
through (7), respectively; and
0
b. Adding new paragraph (b)(3).
    The addition reads as follows:


Sec.  493.801  Condition: Enrollment and testing of samples.

* * * * *
    (b) * * *
    (3) The laboratory must report PT results for microbiology organism 
identification to the highest level that it reports results on patient 
specimens.
* * * * *

0
6. Amend Sec.  493.861 by revising paragraph (a) to read as follows:


Sec.  493.861  Standard; Unexpected antibody detection.

    (a) Failure to attain an overall testing event score of at least 
100 percent is unsatisfactory performance.
* * * * *

0
7. Amend Sec.  493.901 by--
0
a. Redesignating paragraphs (a), (b), (c), and (d) as paragraphs (b), 
(c), (d), and (e), respectively;
0
b. Adding new paragraph (a);
0
c. In newly redesignated paragraph (c)(7) by removing ``;'' and adding 
in its place ``; and'';
0
d. Adding new paragraph (c)(8);
0
e. Revising newly redesignated paragraph (e); and
0
f. Adding new paragraph (f).
    The additions and revisions read as follows:


Sec.  493.901  Approval of proficiency testing programs.

* * * * *
    (a) Require a minimum of 10 laboratory participants for each 
specialty, subspecialty, and analyte or test for which the proficiency 
testing program is seeking reapproval;
* * * * *
    (c) * * *
    (8) A contractor performing technical and scientific 
responsibilities as described in this section and Sec.  493.903 
(including, but not limited to, processes for selecting appropriate 
target values to be included in challenges as part of the annual PT 
program or grading PT results, determining target values, reporting 
scores to CMS, and determining organisms included in microbiology PT 
samples) must be a private nonprofit organization or a Federal or State 
agency, or an entity acting as a designated agent for the Federal or 
State agency.
* * * * *
    (e) HHS may require on-site visits for all initial proficiency 
testing program applications for CMS approval and

[[Page 41233]]

periodically or when problems are encountered for previously HHS-
approved proficiency testing programs either during the reapproval 
process or as necessary to review and verify the policies and 
procedures represented in its application and other information, 
including, but not limited to, review and examination of documents and 
interviews of staff.
    (f) HHS may require a proficiency testing program to reapply for 
approval using the process for initial applications if significant 
problems are encountered during the reapproval process.

0
8. Amend Sec.  493.903 by--
0
a. In paragraph (a)(1) by removing the period and adding ``;'';
0
b. In paragraph (a)(2) by removing ``;'' and adding in its place ``; 
and''; and
0
c. By adding new paragraph (a)(3).
    The addition reads as follows:


Sec.  493.903  Administrative responsibilities.

* * * * *
    (a) * * *
    (3) Not change submitted laboratory data and results for any 
proficiency testing event;
* * * * *

0
9. Section 493.905 is revised to read as follows:


Sec.  493.905  Nonapproved proficiency testing programs.

    (a) Effect on approval status. If a proficiency testing program is 
determined by HHS to fail to meet any criteria contained in Sec. Sec.  
493.901 through 493.959 for approval of the proficiency testing 
program, CMS will notify the program of its withdrawal of approval. 
Approval of the PT program remains in effect for 60 days from the date 
of notification. The proficiency testing program must notify all of its 
participating laboratories of the withdrawal of approval within 30 days 
from the date of notification. CMS may disapprove any proficiency 
testing program that provides false or misleading information with 
respect to any information that is necessary to meet any criteria 
contained in Sec. Sec.  493.901 through 493.959 for approval of the 
proficiency testing program.
    (b) Request for reconsideration. Any proficiency testing program 
that is dissatisfied with a determination to disapprove the program may 
request that CMS reconsider the determination, in accordance with 
subpart D of part 488.

0
10. Section 493.911 is revised to read as follows:


Sec.  493.911  Bacteriology.

    (a) Program content and frequency of challenge. To be approved for 
proficiency testing for bacteriology, the annual program must provide a 
minimum of five samples per testing event. There must be at least three 
testing events provided to the laboratory at approximately equal 
intervals per year. The samples may be provided to the laboratory 
through mailed shipments. The specific organisms included in the 
samples may vary from year to year.
    (1) The annual program must include, as applicable, samples for:
    (i) Gram stain including bacterial morphology;
    (ii) Direct bacterial antigen detection;
    (iii) Bacterial toxin detection; and,
    (iv) Detection and identification of bacteria which includes one of 
the following:
    (A) Detection of the presence or absence of bacteria without 
identification; or
    (B) Identification of bacteria; and
    (v) Antimicrobial susceptibility testing of select bacteria.
    (2) An approved program must furnish HHS and its agents with a 
description of samples that it plans to include in its annual program 
no later than 6 months before each calendar year. The program must 
include bacteria commonly occurring in patient specimens and other 
important emerging pathogens. The program determines the reportable 
isolates and correct responses for antimicrobial susceptibility testing 
for any designated isolate. At least 25 percent of the samples must be 
mixtures of the principal organism and appropriate normal flora. Mixed 
cultures are samples that require reporting of one or more principal 
pathogens. Mixed cultures are not ``negative'' samples such as when two 
commensal organisms are provided in a PT sample with the intended 
response of ``negative'' or ``no pathogen present.'' The program must 
include the following two types of samples to meet the 25 percent mixed 
culture criterion:
    (i) Samples that require laboratories to report only organisms that 
the testing laboratory considers to be a principal pathogen that is 
clearly responsible for a described illness (excluding immuno-
compromised patients). The program determines the reportable isolates, 
including antimicrobial susceptibility for any designated isolate; and
    (ii) Samples that require laboratories to report all organisms 
present. Samples must contain multiple organisms frequently found in 
specimens where multiple isolates are clearly significant or where 
specimens are derived from immuno-compromised patients. The program 
determines the reportable isolates.
    (3) The content of an approved program must vary over time, as 
appropriate. The types of bacteria included annually must be 
representative of the following major groups of medically important 
aerobic and anaerobic bacteria, if appropriate for the sample sources:
    (i) Gram-negative bacilli.
    (ii) Gram-positive bacilli.
    (iii) Gram-negative cocci.
    (iv) Gram-positive cocci.
    (4) For antimicrobial susceptibility testing, the program must 
provide at least two samples per testing event. The program must 
annually provide samples that include Gram-positive organisms and 
samples that include Gram-negative organisms that have a predetermined 
pattern of susceptibility or resistance to the common antimicrobial 
agents.
    (b) Evaluation of a laboratory's performance. HHS approves only 
those programs that assess the accuracy of a laboratory's responses in 
accordance with paragraphs (b)(1) through (9) of this section.
    (1) The program determines the reportable bacterial staining and 
morphological characteristics to be interpreted by Gram stain. The 
program determines the bacteria to be reported by direct bacterial 
antigen detection, bacterial toxin detection, detection of the presence 
or absence of bacteria without identification, identification of 
bacteria, and antimicrobial susceptibility testing. To determine the 
accuracy of each of the laboratory's responses, the program must 
compare each response with the response which reflects agreement of 
either 80 percent or more of 10 or more referee laboratories or 80 
percent or more of all participating laboratories. Both methods must be 
attempted before the program can choose to not grade a PT sample.
    (2) A laboratory must identify the organisms to highest level that 
the laboratory reports results on patient specimens.
    (3) A laboratory's performance will be evaluated on the basis of 
the average of its scores for paragraph (b)(4) through (8) of this 
section as determined in paragraph (b)(9) of this section.
    (4) The performance criteria for Gram stain including bacterial 
morphology is staining reaction, that is, Gram positive or Gram 
negative and morphological description for each sample. The score is 
the number of correct responses for Gram stain reaction plus the number 
of correct responses for morphological description divided by 2 then 
divided by the number of samples to be tested, multiplied by 100.

[[Page 41234]]

    (5) The performance criterion for direct bacterial antigen 
detection is the presence or absence of the bacterial antigen. The 
score is the number of correct responses divided by the number of 
samples to be tested, multiplied by 100.
    (6) The performance criterion for bacterial toxin detection is the 
presence or absence of the bacterial toxin. The score is the number of 
correct responses divided by the number of samples to be tested 
multiplied by 100.
    (7) The performance criterion for the detection and identification 
of bacteria includes one of the following:
    (i) The performance criterion for the detection of the presence or 
absence of bacteria without identification is the correct detection of 
the presence or absence of bacteria without identification. The score 
is the number of correct responses divided by the number of samples to 
be tested multiplied by 100.
    (ii) The performance criterion for the identification of bacteria 
is the total number of correct responses for bacterial identification 
submitted by the laboratory divided by the number of organisms present 
plus the number of incorrect organisms reported by the laboratory 
multiplied by 100 to establish a score for each sample in each testing 
event. Since laboratories may incorrectly report the presence of 
organisms in addition to the correctly identified principal 
organism(s), the scoring system must provide a means of deducting 
credit for additional erroneous organisms that are reported. For 
example, if a sample contained one principal organism and the 
laboratory reported it correctly but reported the presence of an 
additional organism, which was not considered reportable, the sample 
grade would be 1/(1+1) x 100 = 50 percent.
    (8) For antimicrobial susceptibility testing, a laboratory must 
indicate which drugs are routinely included in its test panel when 
testing patient samples. A laboratory's performance will be evaluated 
for only those antimicrobials for which susceptibility testing is 
routinely performed on patient specimens. A correct response for each 
antimicrobial will be determined as described in paragraph (b)(1) of 
this section. Scoring for each sample is based on the number of correct 
susceptibility responses reported by the laboratory divided by the 
actual number of correct susceptibility responses determined by the 
program, multiplied by 100. For example, if a laboratory offers 
susceptibility testing using three antimicrobial agents, and the 
laboratory reports correct responses for two of the three antimicrobial 
agents, the laboratory's grade would be \2/3\ x 100 = 67 percent.
    (9) The score for a testing event in bacteriology is the average of 
the scores determined under paragraphs (b)(4) through (8) of this 
section based on the type of service offered by the laboratory.

0
11. Section 493.913 is revised to read as follows:


Sec.  493.913  Mycobacteriology.

    (a) Program content and frequency of challenge. To be approved for 
proficiency testing for mycobacteriology, the annual program must 
provide a minimum of five samples per testing event. There must be at 
least two testing events provided to the laboratory at approximately 
equal intervals per year. The samples may be provided through mailed 
shipments. The specific organisms included in the samples may vary from 
year to year.
    (1) The annual program must include, as applicable, samples for:
    (i) Acid-fast stain; and
    (ii) Detection and identification of mycobacteria which includes 
one of the following:
    (A) Detection of the presence or absence of mycobacteria without 
identification; or
    (B) Identification of mycobacteria.
    (2) An approved program must furnish HHS and its agents with a 
description of the samples it plans to include in its annual program no 
later than 6 months before each calendar year. At least 25 percent of 
the samples must be mixtures of the principal mycobacteria and 
appropriate normal flora. The program must include mycobacteria 
commonly occurring in patient specimens and other important emerging 
mycobacteria. The program determines the reportable isolates and 
correct responses.
    (3) The content of an approved program may vary over time, as 
appropriate. The mycobacteria included annually must contain species 
representative of the following major groups of medically important 
mycobacteria, if appropriate for the sample sources:
    (i) Mycobacterium tuberculosis complex; and
    (ii) Mycobacterium other than tuberculosis (MOTT).
    (4) The program must provide at least five samples per testing 
event that include challenges that contain acid-fast organisms and 
challenges that do not contain acid-fast organisms.
    (b) Evaluation of a laboratory's performance. HHS approves only 
those programs that assess the accuracy of a laboratory's response in 
accordance with paragraphs (b)(1) through (6) of this section.
    (1) The program determines the reportable mycobacteria to be 
detected by acid-fast stain. The program determines the mycobacteria to 
be reported by detection of the presence or absence of mycobacteria 
without identification, and identification of mycobacteria. To 
determine the accuracy of each of the laboratory's responses, the 
program must compare each response with the response that reflects 
agreement of either 80 percent or more of 10 or more referee 
laboratories or 80 percent or more of all participating laboratories. 
Both methods must be attempted before the program can choose to not 
grade a PT sample.
    (2) A laboratory must detect and identify the organisms to the 
highest level that the laboratory reports results on patient specimens.
    (3) A laboratory's performance will be evaluated on the basis of 
the average of its scores for paragraph (b)(4) through (5) of this 
section as determined in paragraph (b)(6) of this section.
    (4) The performance criterion for acid-fast stains is positive or 
negative or the presence or absence of acid-fast organisms. The score 
is the number of correct responses divided by the number of samples to 
be tested, multiplied by 100.
    (5) The performance criterion for the detection and identification 
of mycobacteria includes one of the following:
    (i) The performance criterion for the detection of the presence or 
absence of mycobacteria without identification is the correct detection 
of the presence or absence of mycobacteria without identification. The 
score is the number of correct responses divided by the number of 
samples to be tested multiplied by 100.
    (ii) The performance criterion for the identification of 
mycobacteria is the total number of correct responses for mycobacterial 
identification submitted by the laboratory divided by the number of 
organisms present plus the number of incorrect organisms reported by 
the laboratory multiplied by 100 to establish a score for each sample 
in each testing event. Since laboratories may incorrectly report the 
presence of mycobacteria in addition to the correctly identified 
principal organism(s), the scoring system must provide a means of 
deducting credit for additional erroneous organisms reported. For 
example, if a sample contained one principal organism and the 
laboratory reported it correctly but reported the presence of an 
additional organism, which was not considered

[[Page 41235]]

reportable, the sample grade would be 1/(1+1) x 100 = 50 percent.
    (6) The score for a testing event in mycobacteriology is the 
average of the scores determined under paragraphs (b)(4) through (5) of 
this section based on the type of service offered by the laboratory.

0
12. Section 493.915 is revised to read as follows:


Sec.  493.915  Mycology.

    (a) Program content and frequency of challenge. To be approved for 
proficiency testing for mycology, the annual program must provide a 
minimum of five samples per testing event. There must be at least three 
testing events provided to the laboratory at approximately equal 
intervals per year. The samples may be provided through mailed 
shipments. The specific organisms included in the samples may vary from 
year to year.
    (1) The annual program must include, as applicable, samples for:
    (i) Direct fungal antigen detection; and
    (ii) Detection and identification of fungi and aerobic 
actinomycetes which includes one of the following:
    (A) Detection of the presence or absence of fungi and aerobic 
actinomycetes without identification; or
    (B) Identification of fungi and aerobic actinomycetes.
    (2) An approved program must furnish HHS and its agents with a 
description of the samples it plans to include in its annual program no 
later than 6 months before each calendar year. At least 25 percent of 
the samples must be mixtures of the principal organism and appropriate 
normal background flora. The program must include fungi and aerobic 
actinomycetes commonly occurring in patient specimens and other 
important emerging fungi. The program determines the reportable 
isolates and correct responses.
    (3) The content of an approved program must vary over time, as 
appropriate. The fungi included annually must contain species 
representative of the following major groups of medically important 
fungi and aerobic actinomycetes, if appropriate for the sample sources:
    (i) Yeast or yeast-like organisms;
    (ii) Molds that include;
    (A) Dematiaceous fungi;
    (B) Dermatophytes;
    (C) Hyaline hyphomycetes;
    (D) Mucormycetes; and
    (iii) Aerobic actinomycetes.
    (b) Evaluation of a laboratory's performance. HHS approves only 
those programs that assess the accuracy of a laboratory's response, in 
accordance with paragraphs (b)(1) through (6) of this section.
    (1) The program determines the reportable fungi to be reported by 
direct fungal antigen detection, detection of the presence or absence 
of fungi and aerobic actinomycetes without identification, and 
identification of fungi and aerobic actinomycetes. To determine the 
accuracy of a laboratory's responses, the program must compare each 
response with the response reflects agreement of either 80 percent or 
more of 10 or more referee laboratories or 80 percent or more of all 
participating laboratories. Both methods must be attempted before the 
program can choose to not grade a PT sample.
    (2) A laboratory must detect and identify the organisms to highest 
level that the laboratory reports results on patient specimens.
    (3) A laboratory's performance will be evaluated on the basis of 
the average of its scores for paragraphs (b)(4) through (5) of this 
section as determined in paragraph (b)(6) of this section.
    (4) The performance criterion for direct fungal antigen detection 
is the presence or absence of the fungal antigen. The score is the 
number of correct responses divided by the number of samples to be 
tested, multiplied by 100.
    (5) The performance criterion for the detection and identification 
of fungi and aerobic actinomycetes includes one of the following:
    (i) The performance criterion for the detection of the presence or 
absence of fungi and aerobic actinomycetes without identification is 
the correct detection of the presence or absence of fungi and aerobic 
actinomycetes without identification. The score is the number of 
correct responses divided by the number of samples to be tested 
multiplied by 100.
    (ii) The performance criterion for the identification of fungi and 
aerobic actinomycetes is the total number of correct responses for 
fungal and aerobic actinomycetes identification submitted by the 
laboratory divided by the number of organisms present plus the number 
of incorrect organisms reported by the laboratory multiplied by 100 to 
establish a score for each sample in each testing event. Since 
laboratories may incorrectly report the presence of fungi and aerobic 
actinomycetes in addition to the correctly identified principal 
organism(s), the scoring system must provide a means of deducting 
credit for additional erroneous organisms that are reported. For 
example, if a sample contained one principal organism and the 
laboratory reported it correctly but reported the presence of an 
additional organism, which was not considered reportable, the sample 
grade would be 1/(1+1) x 100 = 50 percent.
    (6) The score for a testing event is the average of the sample 
scores as determined under paragraphs (b)(4) through (5) of this 
section.

0
13. Section 493.917 is revised to read as follows:


Sec.  493.917  Parasitology.

    (a) Program content and frequency of challenge. To be approved for 
proficiency testing for parasitology, the annual program must provide a 
minimum of five samples per testing event. There must be at least three 
testing events provided to the laboratory at approximately equal 
intervals per year. The samples may be provided through mailed 
shipments. The specific organisms included in the samples may vary from 
year to year.
    (1) The annual program must include, as applicable, samples for:
    (i) Direct parasite antigen detection; and
    (ii) Detection and identification of parasites which includes one 
of the following:
    (A) Detection of the presence or absence of parasites without 
identification; or
    (B) Identification of parasites.
    (2) An approved program must furnish HHS and its agents with a 
description of the samples it plans to include in its annual program no 
later than 6 months before each calendar year. Samples must include 
both formalinized specimens and PVA (polyvinyl alcohol) fixed specimens 
as well as blood smears, as appropriate for a particular parasite and 
stage of the parasite. The majority of samples must contain protozoa or 
helminths or a combination of parasites. Some samples must be devoid of 
parasites.
    (3) The content of an approved program must vary over time, as 
appropriate. The types of parasites included annually must be 
representative of the following major groups of medically important 
parasites, if appropriate for the sample sources:
    (i) Intestinal parasites; and
    (ii) Blood and tissue parasites.
    (4) The program must provide at least five samples per testing 
event that include challenges that contain parasites and challenges 
that are devoid of parasites.
    (b) Evaluation of a laboratory's performance. HHS approves only 
those programs that assess the accuracy of a laboratory's responses in 
accordance with paragraphs (b)(1) through (6) of this section.

[[Page 41236]]

    (1) The program determines the reportable parasites to be detected 
by direct parasite antigen detection, detection of the presence or 
absence of parasites without identification, and identification of 
parasites. It may elect to establish a minimum number of parasites to 
be identified in samples before they are reported. Parasites found in 
rare numbers by referee laboratories are not considered in a 
laboratory's performance; such findings are neutral. To determine the 
accuracy of a laboratory's response, the program must compare each 
response with the response which reflects agreement of either 80 
percent or more of 10 or more referee laboratories or 80 percent or 
more of all participating laboratories. Both methods must be attempted 
before the program can choose to not grade a PT sample.
    (2) A laboratory must detect and identify or concentrate and 
identify the parasites to the highest level that the laboratory reports 
results on patient specimens.
    (3) A laboratory's performance will be evaluated on the basis of 
the average of its scores for paragraphs (b)(4) through (5) of this 
section as determined in paragraph (b)(6) of this section.
    (4) The performance criterion for direct parasite antigen detection 
is the presence or absence of the parasite antigen. The score is the 
number of correct responses divided by the number of samples to be 
tested, multiplied by 100.
    (5) The performance criterion for the detection and identification 
of parasites includes one of the following:
    (i) The performance criterion for the detection of the presence or 
absence of parasites without identification is the correct detection of 
the presence or absence of parasites without identification. The score 
is the number of correct responses divided by the number of samples to 
be tested, multiplied by 100.
    (ii) The performance criterion for the identification of parasites 
is the total number of correct responses for parasite identification 
submitted by the laboratory divided by the number of parasites present 
plus the number of incorrect parasites reported by the laboratory 
multiplied by 100 to establish a score for each sample in each testing 
event. Since laboratories may incorrectly report the presence of 
parasites in addition to the correctly identified principal 
organism(s), the scoring system must provide a means of deducting 
credit for additional erroneous organisms that are reported and not 
found in rare numbers by the program's referencing process. For 
example, if a sample contained one principal organism and the 
laboratory reported it correctly but reported the presence of an 
additional organism, which was not considered reportable, the sample 
grade would be 1/(1+1) x 100 = 50 percent.
    (6) The score for a testing event is the average of the sample 
scores as determined under paragraphs (b)(4) through (5) of this 
section.

0
14. Section 493.919 is revised to read as follows:


Sec.  493.919  Virology.

    (a) Program content and frequency of challenge. To be approved for 
proficiency testing for virology, a program must provide a minimum of 
five samples per testing event. There must be at least three testing 
events at approximately equal intervals per year. The samples may be 
provided to the laboratory through mailed shipments. The specific 
organisms included in the samples may vary from year to year.
    (1) The annual program must include, as applicable, samples for:
    (i) Viral antigen detection; and
    (ii) Detection and identification of viruses.
    (2) An approved program must furnish HHS and its agents with a 
description of the samples it plans to include in its annual program no 
later than 6 months before each calendar year. The program must include 
other important emerging viruses and viruses commonly occurring in 
patient specimens.
    (3) The content of an approved program must vary over time, as 
appropriate. If appropriate for the sample sources, the types of 
viruses included annually must be representative of the following major 
groups of medically important viruses:
    (i) Respiratory viruses;
    (ii) Herpes viruses;
    (iii) Enterovirus; and
    (iv) Intestinal viruses.
    (b) Evaluation of laboratory's performance. HHS approves only those 
programs that assess the accuracy of a laboratory's response in 
accordance with paragraphs (b)(1) through (6) of this section.
    (1) The program determines the viruses to be reported by direct 
viral antigen detection, and detection and identification of viruses. 
To determine the accuracy of a laboratory's response, the program must 
compare each response with the response which reflects agreement of 
either 80 percent or more of 10 or more referee laboratories or 80 
percent or more of all participating laboratories. Both methods must be 
attempted before the program can choose to not grade a PT sample.
    (2) A laboratory must detect and identify the viruses to the 
highest level that the laboratory reports results on patient specimens.
    (3) A laboratory's performance will be evaluated on the basis of 
the average of its scores for paragraphs (b)(4) through (5) of this 
section as determined in paragraph (b)(6) of this section.
    (4) The performance criterion viral antigen detection is the 
presence or absence of the viral antigen. The score is the number of 
correct responses divided by the number of samples to be tested, 
multiplied by 100.
    (5) The performance criterion for the detection and identification 
of viruses is the total number of correct responses for viral detection 
and identification submitted by the laboratory divided by the number of 
viruses present plus the number of incorrect virus reported by the 
laboratory multiplied by 100 to establish a score for each sample in 
each testing event. Since laboratories may incorrectly report the 
presence of viruses in addition to the correctly identified principal 
organism(s), the scoring system must provide a means of deducting 
credit for additional erroneous organisms that are reported. For 
example, if a sample contained one principal organism and the 
laboratory reported it correctly but reported the presence of an 
additional organism, which was not considered reportable, the sample 
grade would be 1/(1+1) x 100 = 50 percent.
    (6) The score for a testing event is the average of the sample 
scores as determined under paragraphs (b)(4) and (5) of this section.

0
15. Amend Sec.  493.923 by revising paragraphs (a) and (b)(1) to read 
as follows:


Sec.  493.923  Syphilis serology.

    (a) Program content and frequency of challenge. To be approved for 
proficiency testing for syphilis serology, a program must provide a 
minimum of five samples per testing event. There must be at least three 
testing events at approximately equal intervals per year. The samples 
may be provided through mailed shipments. An annual program must 
include samples that cover the full range of reactivity from highly 
reactive to non-reactive.
    (b) * * *
    (1) To determine the accuracy of a laboratory's response for 
qualitative and quantitative syphilis tests, the program must compare 
the laboratory's response with the response that reflects agreement of 
either 80 percent or more of 10 or more referee laboratories or 80

[[Page 41237]]

percent or more of all participating laboratories. Both methods must be 
attempted before the program can choose to not grade a PT sample.
* * * * *

0
16. Amend Sec.  493.927 by revising paragraphs (a), (b), (c)(1), and 
(2) to read as follows:


Sec.  493.927  General immunology.

    (a) Program content and frequency of challenge. To be approved for 
proficiency testing for immunology, the annual program must provide a 
minimum of five samples per testing event. There must be at least three 
testing events at approximately equal intervals per year. The annual 
program must provide samples that cover the full range of reactivity 
from highly reactive to nonreactive. The samples may be provided 
through mailed shipments.
    (b) Challenges per testing event. The minimum number of challenges 
per testing event the program must provide for each analyte or test 
procedure is five. Analytes or tests for which laboratory performance 
is to be evaluated include:

           Table 1 to Paragraph (b)--Analyte or Test Procedure
------------------------------------------------------------------------
 
-------------------------------------------------------------------------
Alpha-l antitrypsin.
Alpha-fetoprotein (tumor marker).
Antinuclear antibody.
Antistreptolysin O (ASO).
Anti-human immunodeficiency virus (HIV).
Complement C3.
Complement C4.
C-reactive protein (high sensitivity).
HBsAg.
Anti-HBc.
HBeAg.
Anti-HBs.
Anti-HCV.
IgA.
IgG.
IgE.
IgM.
Infectious mononucleosis.
Rheumatoid factor.
Rubella.
------------------------------------------------------------------------

    (c) * * *
    (1) To determine the accuracy of a laboratory's response for 
quantitative and qualitative immunology tests or analytes, the program 
must compare the laboratory's response for each analyte with the 
response that reflects agreement of either 80 percent or more of 10 or 
more referee laboratories or 80 percent or more of all participating 
laboratories. The proficiency testing program must indicate the minimum 
concentration that will be considered as indicating a positive 
response. Both methods must be attempted before the program can choose 
to not grade a PT sample.
    (2) For quantitative immunology analytes or tests, the program must 
determine the correct response for each analyte by the distance of the 
response from the target value. After the target value has been 
established for each response, the appropriateness of the response must 
be determined by using either fixed criteria or the number of standard 
deviations (SDs) the response differs from the target value.

    Table 2 to Paragraph (c)(2)--Criteria for Acceptable Performance
------------------------------------------------------------------------
    The criteria for acceptable
 performance are-- Analyte or test   Criteria for acceptable performance
------------------------------------------------------------------------
Alpha-1 antitrypsin...............  Target value  20%.
Alpha-fetoprotein (tumor marker)..  Target value  20%.
Antinuclear antibody (ANA)........  Target value 2 dilutions
                                     or positive or negative.
Antistreptolysin O................  Target value 2 dilutions
                                     or positive or negative.
Anti-Human Immunodeficiency virus   Reactive (positive) or nonreactive
 (HIV).                              (negative).
Complement C3.....................  Target value 15%.
Complement C4.....................  Target value 20% or
                                     5 mg/dL (greater).
C-reactive protein (HS)...........  Target value 30% or
                                     1 mg/L (greater).
HBsAg.............................  Reactive (positive) or nonreactive
                                     (negative).
Anti-HBc..........................  Reactive (positive) or nonreactive
                                     (negative).
HBeAg.............................  Reactive (positive) or nonreactive
                                     (negative).
Anti-HBs..........................  Reactive (positive) or nonreactive
                                     (negative).
Anti-HCV..........................  Reactive (positive) or nonreactive
                                     (negative).
IgA...............................  Target value 20%.
IgE...............................  Target value 20%.
IgG...............................  Target value 20%.
IgM...............................  Target value 20%.
Infectious mononucleosis..........  Target value 2 dilutions
                                     or positive or negative.
Rheumatoid factor.................  Target value 2 dilutions
                                     or positive or negative.
Rubella...........................  Target value 2 dilutions
                                     or positive or negative or immune
                                     or nonimmune.
------------------------------------------------------------------------


[[Page 41238]]

* * * * *

0
17. Amend Sec.  493.931 by revising paragraphs (a), (b), (c)(1) and (2) 
to read as follows:


Sec.  493.931  Routine chemistry.

    (a) Program content and frequency of challenge. To be approved for 
proficiency testing for routine chemistry, a program must provide a 
minimum of five samples per testing event. There must be at least three 
testing events at approximately equal intervals per year. The annual 
program must provide samples that cover the clinically relevant range 
of values that would be expected in patient specimens. The specimens 
may be provided through mailed shipments.
    (b) Challenges per testing event. The minimum number of challenges 
per testing event a program must provide for each analyte or test 
procedure listed below is five serum, plasma or blood samples.

           Table 1 to Paragraph (b)--Analyte or Test Procedure
------------------------------------------------------------------------
 
-------------------------------------------------------------------------
Alanine aminotransferase (ALT/SGPT).
Albumin.
Alkaline phosphatase.
Amylase.
Aspartate aminotransferase (AST/SGOT).
Bilirubin, total.
Blood gas (pH, pO2, and pCO2).
B-natriuretic peptide (BNP).
proBNP.
Calcium, total.
Carbon dioxide.
Chloride.
Cholesterol, total.
Cholesterol, high density lipoprotein.
Cholesterol, low density lipoprotein, (direct measurement).
Creatine kinase (CK).
CK-MB isoenzymes.
Creatinine.
Ferritin.
Gamma glutamyl transferase.
Glucose (Excluding measurements on devices cleared by FDA for home use).
Hemoglobin A1c.
Iron, total.
Lactate dehydrogenase (LDH).
Magnesium.
Phosphorus.
Potassium.
Prostate specific antigen (PSA), total.
Sodium.
Total iron binding capacity (TIBC) (direct measurement).
Total Protein.
Triglycerides.
Troponin I.
Troponin T.
Urea Nitrogen.
Uric Acid.
------------------------------------------------------------------------

    (c) * * *
    (1) To determine the accuracy of a laboratory's response for 
qualitative and quantitative chemistry tests or analytes, the program 
must compare the laboratory's response for each analyte with the 
response that reflects agreement of either 80 percent or more of 10 or 
more referee laboratories or 80 percent or more of all participating 
laboratories. Both methods must be attempted before the program can 
choose to not grade a PT sample.
    (2) For quantitative chemistry tests or analytes, the program must 
determine the correct response for each analyte by the distance of the 
response from the target value. After the target value has been 
established for each response, the appropriateness of the response must 
be determined by using either fixed criteria based on the percentage 
difference from the target value or the number of standard deviations 
(SD) the response differs from the target value.

    Table 2 to Paragraph (c)(2)--Criteria for Acceptable Performance
------------------------------------------------------------------------
    The criteria for acceptable
 performance are-- Analyte or test   Criteria for acceptable performance
------------------------------------------------------------------------
Alanine aminotransferase (ALT/      Target value 15% or
 SGPT).                              6 U/L (greater).
Albumin...........................  Target value 8%.
Alkaline phosphatase..............  Target value 20%.
Amylase...........................  Target value 20%.
Aspartate aminotransferase (AST/    Target value 15% or
 SGOT).                              6 U/L (greater).
Bilirubin, total..................  Target value 20% or
                                     0.4 mg/dL (greater).
Blood gas pCO2....................  Target value 8% or 5 mm Hg (greater).
Blood gas pO2.....................  Target value 15% or
                                     15 mmHg (greater).

[[Page 41239]]

 
Blood gas pH......................  Target value 0.04.
B-natriuretic peptide (BNP).......  Target value 30%.
Pro B-natriuretic peptide (proBNP)  Target value 30%.
Calcium, total....................  Target value 1.0 mg/dL.
Carbon dioxide....................  Target value 20%.
Chloride..........................  Target value 5%.
Cholesterol, total................  Target value 10%.
Cholesterol, high density           Target value 20% or
 lipoprotein (HDL).                  6 mg/dL (greater).
Cholesterol, low density            Target value 20%.
 lipoprotein (LDL), direct
 measurement.
Creatine kinase (CK)..............  Target value 20%.
CK-MB isoenzymes..................  Target value  25% or
                                     3 ng/mL (greater) or MB
                                     elevated (presence or absence).
Creatinine........................  Target value 10% or
                                     0.2 mg/dL (greater).
Ferritin..........................  Target value 20%.
Gamma glutamyl transferase........  Target value 15% or
                                     5 U/L (greater).
Glucose (excluding measurements     Target value 8% or 6 mg/dL (greater).
 use.).
Hemoglobin A1c....................  Target value 8%.
Iron, total.......................  Target value 15%.
Lactate dehydrogenase (LDH).......  Target value 15%.
Magnesium.........................  Target value 15%.
Phosphorus........................  Target value  10% or
                                     0.3 mg/dL (greater).
Potassium.........................  Target value 0.3 mmol/L.
Prostate Specific Antigen, total..  Target value 20% or
                                     0.2 ng/mL (greater).
Sodium............................  Target value 4 mmol/L.
Total Iron Binding Capacity         Target value 20%.
 (TIBC). (direct measurement).
Total Protein.....................  Target value 8%.
Triglycerides.....................  Target value 15%.
Troponin I........................  Target value  30% or
                                     0.9 ng/mL (greater).
Troponin T........................  Target value 30% or
                                     0.2 ng/mL (greater).
Urea nitrogen.....................  Target value 9% or 2 mg/dL (greater).
Uric acid.........................  Target value 10%.
------------------------------------------------------------------------

* * * * *

0
18. Amend Sec.  493.933 by revising paragraphs (a), (b), (c)(1), and 
(2) to read as follows:


Sec.  493.933  Endocrinology.

    (a) Program content and frequency of challenge. To be approved for 
proficiency testing for endocrinology, a program must provide a minimum 
of five samples per testing event. There must be at least three testing 
events at approximately equal intervals per year. The annual program 
must provide samples that cover the clinically relevant range of values 
that would be expected in patient specimens. The samples may be 
provided through mailed shipments.
    (b) Challenges per testing event. The minimum number of challenges 
per testing event a program must provide for each analyte or test 
procedure is five serum, plasma, blood, or urine samples.

                Table 1 to Paragraph (b)--Analyte or Test
------------------------------------------------------------------------
 
-------------------------------------------------------------------------
Cancer antigen (CA) 125.
Carcinoembryonic antigen (CEA).
Cortisol.
Estradiol.
Folate, serum.
Follicle stimulating hormone.
Free thyroxine.
Human chorionic gonadotropin (HCG) (excluding urine pregnancy tests done
 by visual color comparison categorized as waived tests).
Luteinizing hormone.
Parathyroid hormone.
Progesterone.
Prolactin.
Testosterone.
T3 Uptake.
Triiodothyronine.
Thyroid-stimulating hormone.
Thyroxine.
Vitamin B12.
------------------------------------------------------------------------

    (c) * * *
    (1) To determine the accuracy of a laboratory's response for 
qualitative and quantitative endocrinology tests or analytes, a program 
must compare the laboratory's response for each analyte with the 
response that reflects agreement of either 80 percent or more of 10 or 
more referee laboratories or 80

[[Page 41240]]

percent or more of all participating laboratories. Both methods must be 
attempted before the program can choose to not grade a PT sample.
    (2) For quantitative endocrinology tests or analytes, the program 
must determine the correct response for each analyte by the distance of 
the response from the target value. After the target value has been 
established for each response, the appropriateness of the response must 
be determined by using either fixed criteria based on the percentage 
difference from the target value or the number of standard deviations 
(SDs) the response differs from the target value.

     Table 2 to Paragraph (c)(2)-Criteria for Acceptable Performance
------------------------------------------------------------------------
    The criteria for acceptable
 performance are-- Analyte or test   Criteria for acceptable performance
------------------------------------------------------------------------
Cancer antigen (CA) 125...........  Target value 20%.
Carcinoembryonic antigen (CEA)....  Target value 15% or
                                     1 ng/dL (greater).
Cortisol..........................  Target value 20%.
Estradiol.........................  Target value 30%.
Folate, serum.....................  Target value 30% or
                                     1 ng/mL (greater).
Follicle stimulating hormone......  Target value 18% or
                                     2 IU/L (greater).
Free thyroxine....................  Target value or 15% or
                                     0.3 ng/dL (greater).
Human chorionic...................  Target value 18% or
                                     3
gonadotropin (excluding urine       mIU/mL (greater) or positive or
 pregnancy tests done by visual      negative.
 color comparison categorized as
 waived tests).
Luteinizing hormone...............  Target value 20%.
Parathyroid hormone...............  Target value 30%.
Progesterone......................  Target value 25%.
Prolactin.........................  Target value 20%.
Testosterone......................  Target value 30% or
                                     20 ng/dL (greater).
T3 uptake.........................  Target value 18%.
Triiodothyronine..................  Target value 30%.
Thyroid-stimulating hormone.......  Target value 20% or
                                     0.2 mIU/L (greater).
Thyroxine.........................  Target value 20% or
                                     1.0 mcg/dL (greater).
Vitamin B12.......................  Target value 25% or
                                     30 pg/mL (greater).
------------------------------------------------------------------------

* * * * *

0
19. Amend Sec.  493.937 by revising paragraphs (a), (b), (c)(1), and 
(2) to read as follows:


Sec.  493.937  Toxicology.

    (a) Program content and frequency of challenge. To be approved for 
proficiency testing for toxicology, the annual program must provide a 
minimum of five samples per testing event. There must be at least three 
testing events at approximately equal intervals per year. The annual 
program must provide samples that cover the full range of values that 
could occur in patient specimens and that cover the level of clinical 
significance for the particular drug. The samples may be provided 
through mailed shipments.
    (b) Challenges per testing event. The minimum number of challenges 
per testing event a program must provide for each analyte or test 
procedure is five serum, plasma, or blood samples.

           Table 1 to Paragraph (b)--Analyte or Test Procedure
------------------------------------------------------------------------
 
-------------------------------------------------------------------------
Acetaminophen, serum.
Alcohol (blood).
Blood lead.
Carbamazepine, total.
Digoxin, total.
Gentamicin.
Lithium.
Phenobarbital.
Phenytoin, total.
Salicylate.
Theophylline.
Tobramycin.
Valproic Acid, total.
Vancomycin.
------------------------------------------------------------------------

    (c) * * *
    (1) To determine the accuracy of a laboratory's responses for 
quantitative toxicology tests or analytes, the program must compare the 
laboratory's response for each analyte with the response that reflects 
agreement of either 80 percent or more of 10 or more referee 
laboratories or 80 percent or more of all participating laboratories. 
Both methods must be attempted before the program can choose to not 
grade a PT sample.
    (2) For quantitative toxicology tests or analytes, the program must 
determine the correct response for each analyte by the distance of the 
response from the target value. After the target value has been 
established for each response, the appropriateness of the response must 
be determined by using fixed criteria based on the percentage 
difference from the target value.

[[Page 41241]]



    Table 2 to Paragraph (c)(2)--Criteria for Acceptable Performance
------------------------------------------------------------------------
    The criteria for acceptable
 performance are-- Analyte or test   Criteria for acceptable performance
------------------------------------------------------------------------
Acetaminophen.....................  Target value 15% or
                                     3 mcg/mL (greater).
Alcohol, blood....................  Target Value 20%.
Blood lead........................  Target Value 10% or
                                     2 mcg/dL (greater).
Carbamazepine, total..............  Target Value 20% or
                                     1.0 mcg/mL (greater).
Digoxin, total....................  Target Value 15% or
                                      0.2 ng/mL (greater).
Gentamicin........................  Target Value 25%.
Lithium...........................  Target Value 15% or
                                     0.3 mmol/L (greater).
Phenobarbital.....................  Target Value 15% or
                                     2 mcg/mL (greater).
Phenytoin total...................  Target Value 15% or
                                      2 mcg/mL (greater).
Salicylate........................  Target Value 15% or
                                     2 mcg/mL (greater).
Theophylline......................  Target Value 20%.
Tobramycin........................  Target Value 20%.
Valproic Acid, total..............  Target Value 20%.
Vancomycin........................  Target Value 15% or
                                     2 mcg/mL (greater).
------------------------------------------------------------------------

* * * * *

0
20. Amend Sec.  493.941 by revising paragraphs (a), (b), (c)(1) and (2) 
to read as follows:


Sec.  493.941  Hematology (including routine hematology and 
coagulation).

    (a) Program content and frequency of challenge. To be approved for 
proficiency testing for hematology, a program must provide a minimum of 
five samples per testing event. There must be at least three testing 
events at approximately equal intervals per year. The annual program 
must provide samples that cover the full range of values that would be 
expected in patient specimens. The samples may be provided through 
mailed shipments.
    (b) Challenges per testing event. The minimum number of challenges 
per testing event a program must provide for each analyte or test 
procedure is five.

           Table 1 to Paragraph (b)--Analyte or Test Procedure
------------------------------------------------------------------------
 
-------------------------------------------------------------------------
Cell identification.
White blood cell differential.
Erythrocyte count.
Hematocrit (excluding spun microhematocrit).
Hemoglobin.
Leukocyte count.
Platelet count.
Fibrinogen.
Partial thromboplastin time.
Prothrombin time (seconds or INR).
------------------------------------------------------------------------

    (c) * * *
    (1) To determine the accuracy of a laboratory's responses for 
qualitative and quantitative hematology tests or analytes, the program 
must compare the laboratory's response for each analyte with the 
response that reflects agreement of either 80 percent or more of 10 or 
more referee laboratories or 80 percent or more of all participating 
laboratories. Both methods must be attempted before the program can 
choose to not grade a PT sample.
    (2) For quantitative hematology tests or analytes, the program must 
determine the correct response for each analyte by the distance of the 
response from the target value. After the target value has been 
established for each response, the appropriateness of the response is 
determined using either fixed criteria based on the percentage 
difference from the target value or the number of standard deviations 
(SD) the response differs from the target value.

    Table 2 to Paragraph (c)(2)--Criteria for Acceptable Performance
------------------------------------------------------------------------
    The criteria for acceptable
 performance are: Analyte or test    Criteria for acceptable performance
------------------------------------------------------------------------
Cell identification...............  80% or greater consensus on
                                     identification.
White blood cell differential.....  Target 3SD based on the
                                     percentage of different types of
                                     white blood cells in the samples.
Erythrocyte count.................  Target 4%.
Hematocrit (Excluding spun          Target 4%.
 hematocrit).
Hemoglobin........................  Target 4%.
Leukocyte count...................  Target 10%.
Platelet count....................  Target 25%.
Fibrinogen........................  Target 20%.
Partial thromboplastin time.......  Target 15%.
------------------------------------------------------------------------
If a laboratory reports a prothrombin time in both INR and seconds, the
 INR should be reported to the PT provider program.
------------------------------------------------------------------------

[[Page 41242]]

 
Prothrombin time (seconds or INR).  Target 15%.
------------------------------------------------------------------------

* * * * *

0
21. Amend Sec.  493.959 by revising paragraphs (b), (d)(1) and (2) to 
read as follows:


Sec.  493.959  Immunohematology.

* * * * *
    (b) Program content and frequency of challenge. To be approved for 
proficiency testing for immunohematology, a program must provide a 
minimum of five samples per testing event. There must be at least three 
testing events at approximately equal intervals per year. The annual 
program must provide samples that cover the full range of 
interpretation that would be expected in patient specimens. The samples 
may be provided through mailed shipments.
    (d) * * *
    (1) To determine the accuracy of a laboratory's response, a program 
must compare the laboratory's response for each analyte with the 
response that reflects agreement of either 100 percent of 10 or more 
referee laboratories or 95 percent or more of all participating 
laboratories except for antibody identification. To determine the 
accuracy of a laboratory's response for antibody identification, a 
program must compare the laboratory's response for each analyte with 
the response that reflects agreement of either 95 percent or more of 10 
or more referee laboratories or 95 percent or more of all participating 
laboratories. Both methods must be attempted before the program can 
choose to not grade a PT sample.
    (2) Criteria for acceptable performance. The criteria for 
acceptable performance are--

    Table 2 to Paragraph (d)(2)--Criteria for Acceptable Performance
------------------------------------------------------------------------
          Analyte or test            Criteria for acceptable performance
------------------------------------------------------------------------
ABO group.........................  100% accuracy.
D (Rho) typing....................  100% accuracy.
Unexpected antibody detection.....  100% accuracy.
Compatibility testing.............  100% accuracy.
Antibody identification...........  80%+ accuracy.
------------------------------------------------------------------------

* * * * *

    Dated: June 24, 2022.
Xavier Becerra,
Secretary, Department of Health and Human Services.
[FR Doc. 2022-14513 Filed 7-7-22; 4:15 pm]
BILLING CODE 4120-01-P