41194 Federal Register / Vol. 87, No. 131 / Monday, July 11, 2022 / Rules and Regulations 

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. 

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 §§ 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 highcomplexity 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 §§ 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 § 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 § 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, § 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, §§ 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 §§ 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 Grampositive 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 

§§ 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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1https://www.ecfr.gov/current/title-42/chapterIV/subchapter-G/part-493#493.2. 

++ 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. 

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, 

§§ 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, Gramnegative 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, §§ 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; Gramnegative 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 § 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 §§ 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 § 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 


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and summarize our final policies in 

section III.E. of this final rule. 

5. Mixed Culture Requirement 

The current CLIA requirements for 

bacteriology §§ 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 § 493.911(b)(1) and 

mycobacteriology at § 493.913(b)(1), but 

it is not required for mycology, 

parasitology, or virology. For 

antimicrobial susceptibility testing in 

bacteriology at § 493.911(b)(3), at least 

one sample per testing event must 

include one Gram-positive or Gramnegative sample, and for 

mycobacteriology at § 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 Gramnegative 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 §§ 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 


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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 §§ 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 § 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 

§§ 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 

§ 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 § 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 NonMicrobiology 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 §§ 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 

§§ 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 §§ 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 

§ 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 


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2 2009 Truven Health MarketScan® data, https:// 

truvenhealth.com/your-healthcare-focus/lifesciences/data_databases_and_online_toolsMarkets/ 

Life-Sciences/Products/Data-Tools/MarketScanDatabases. 

3https://www.ncbi.nlm.nih.gov/pmc/articles/ 

PMC4698806/. 

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. 

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 abovedescribed 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 


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4http://www.accessdata.fda.gov/scripts/cdrh/ 

cfdocs/cfClia/Search.cfm. 

5https://www.thecommunityguide.org. 

6https://www.ahrq.gov/research/findings/nhqrdr/ 

index.html. 

7https://www.uspreventiveservicestaskforce.org/ 

Page/Name/recommendations. 

8https://www.ahrq.gov/research/findings/nhqrdr/ 

index.html. 

9https://www.cdc.gov/labstandards/hs.html. 

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. 

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. 

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). 

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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 


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TABLE 1 A : na1y It es P ropose di or Add110D 0 u ,pa 0f t S b rt I 

CLIA Regulation Analytes 

General Immunology Anti-HBs 

§ 493.927 Anti-HCV 

C-reactive protein (high sensitivity) 

Routine Chemistry B-natriuretic peptide (BNP) 

§ 493.931 ProBNP 

Cancer antigen (CA) 125 

Carbon dioxide 

Carcinoembryonic antigen 

Cholesterol, low density lipoprotein, direct measurement 

Ferritin 

Gamma glutamyl transferase 

Hemoglobin Ale 

Phosphorus 

Prostate specific antigen, total 

Total iron binding capacity (TIBC), direct measurement 

Troponin I 

Troponin T 

Endocrinology Estradiol 

§ 493.933 Folate, serum 

Follicle stimulating hormone 

Luteinizing hormone 

Progesterone 

Prolactin 

Parathyroid hormone 

Testosterone 

VitaminB12 

Toxicology Acetaminophen, serum 

§ 493.937 Salicylate 

Vancomvcin 
41202 Federal Register / Vol. 87, No. 131 / Monday, July 11, 2022 / Rules and Regulations 

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 § 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 § 493.931 

LDH isoenzymes and at § 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 

§§ 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 § 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 

§§ 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 nonmicrobiology 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 


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10Astles, Tholen, and Mitchell, 2016, https://

www.aacc.org/science-and-practice/annualmeeting-abstracts-archive. 

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 §§ 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 (§ 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 §§ 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. 

Therefore, we proposed to amend ALs 

for certain current analytes as well as 

establish ALs for analytes proposed for 

addition in §§ 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 


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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 (§§ 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 concentrationbased 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 

§ 493.941. Further, § 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, § 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 


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allow for scoring either with 

participants or with referees before 

calling a sample ungradable. 

C. Additional Proposed Changes 

We proposed to amend § 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 

§ 493.801(a) and (b)(7) are not 

applicable. However, we proposed to 

continue to require compliance with 

§ 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 § 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 § 493.901 that contractors 

performing administrative 

responsibilities as described in 

§§ 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 § 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 HHSapproved 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, 


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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 

(§§ 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 §§ 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, §§ 493.20 and 493.25, 

respectively, will be effective 30 days 

after the publication date of this final 

rule. 

B. Definitions (§ 493.2) 

Comment: A commenter stated that 

the term ‘‘unacceptable score,’’ as 

defined at § 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 § 493.2, 

we are not finalizing this term in § 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 timeconsuming. 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 § 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 


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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 

(§§ 493.20(c) and 493.25(d)) 

Comment: A number of commenters 

expressed concerns or requested 

clarification about the proposal to 

amend §§ 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 

§ 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, § 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 

§§ 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 §§ 493.20(c) and 493.25(d). 

• We are finalizing the proposed 

revisions at §§ 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 §§ 493.801 

and 493.861. 

D. PT Program Approval and 

Administration (§§ 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 § 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 HHSapproved 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 § 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 

§ 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 


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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 § 493.801(b)(5)). 

However, based on the comments 

received, we are not finalizing the 

requirement proposed at § 493.901(c)(6). 

Comment: Several commenters 

expressed concerns about the 

requirement proposed at § 493.901(c)(9) 

that a contractor performing 

administrative responsibilities as 

described in §§ 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, ‘‘forprofit’’ 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 §§ 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 

§ 493.901(c)(8), previously proposed at 

§ 493.901(c)(9). 

Comment: While commenters agreed 

with the requirement proposed at 

§§ 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 § 493.901(e) as 

proposed. 

Comment: We received comments 

concerning the requirement proposed at 

§ 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 

§ 493.901(f). 

Comment: Commenters suggested 

clarification was needed regarding the 

requirement proposed at § 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 § 493.903(a)(3) as 

proposed. 

Comment: Commenters expressed 

concerns regarding the potential impact 

on laboratories and PT programs of the 

requirement proposed at § 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 


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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 §§ 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 § 493.901(c)(6). 

E. Proposed Changes to Microbiology PT 

(§§ 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 (§§ 493.911 

through 493.919), including whether a 

test system is FDA-cleared, or analytes 

in non-microbiology specialties or 

subspecialties (§§ 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 §§ 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 

§ 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 

§ 493.911(a)(1)(iv)(A); mycobacteriology 

at § 493.913(a)(1)(ii)(A); and mycology 

at § 493.915(a)(1)(ii)(A) under the 

proposed categories for microorganism 

detection and identification. Similar 

language proposed for parasitology at 

§ 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 

§ 493.911(a)(1)(iv)(A) to ‘‘detection of 

the presence or absence of bacteria 

without identification.’’ We changed the 

language at § 493.913(a)(1)(ii)(A) to 

‘‘detection of the presence or absence of 

mycobacteria without identification, 

‘‘and at § 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 

§§ 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 §§ 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 (§ 493.911), 

mycobacteriology (§ 493.913), and 

mycology (§ 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 


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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 

§ 493.911(a)(1)(ii); mycology at 

§ 493.915(a)(1)(i); parasitology at 

§ 493.917(a)(1)(i); and virology at 

§ 493.919(a)(1)(i). Required PT for toxin 

detection is included in bacteriology at 

§ 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 

§ 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 gramreaction. 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 

§ 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 § 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 § 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 § 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 § 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 § 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 


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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 §§ 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 §§ 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 

§ 493.915(a)(1)(iii) for mycology and at 

§ 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 § 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 

§ 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 


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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 § 493.911(a)(1)(v); 

mycobacteriology at § 493.913(a)(1)(iii); 

mycology at § 493.915(a)(1)(iii); and 

virology at § 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 

§ 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 Gramnegative 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 Grampositive 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 

§ 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 Grampositive 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 §§ 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 §§ 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 §§ 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 

§§ 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 

§ 493.917(a)(1)(ii)(A) to be consistent 

with the other subspecialties. 

• We are finalizing the proposed 

revised requirement at §§ 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 §§ 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 § 493.911(a) through (b) 

related to Gram stains, direct antigen 

detection, bacterial toxin detection, and 

performance and scoring related to 


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direct antigen and bacterial toxin 

detection for the subspecialty of 

bacteriology. 

• We are finalizing the proposed 

addition to § 493.915(a) related to 

requiring direct antigen testing for the 

subspecialty of mycology. 

• We are finalizing the proposed 

addition to § 493.917(a) related to 

requiring direct antigen testing for the 

subspecialty of parasitology. 

• We are finalizing the proposed 

revision to § 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 

§ 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 §§ 493.913, 

493.915, and 493.919. 

F. Proposed Changes to PT for NonMicrobiology Specialties and 

Subspecialties (§§ 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 § 493.931(b) for 

general chemistry, § 493.933(b) for 

endocrinology, and § 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 

§ 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 Creactive protein, as included in the 


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proposed rule. A related comment 

suggested that we should require PT for 

all assays for C-reactive protein. 

Response: Although traditional Creactive 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 Creactive 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 reexamined 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 percentagebased 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 FDAapproved 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. 


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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 CLIArequired 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 accuracybased 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 accuracybased 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 noncommutable. 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 pointof-care cardiac triage testing of potential 

cardiac events in rural settings. The 


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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 


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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 §§ 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 §§ 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 onsite 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 §§ 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. 


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11https://www.bls.gov/oes/tables.htm. 12https://www.bls.gov/oes/tables.htm. 

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 §§ 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 × 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 × $54.72). 

B. Optional On-Site Visits to PT 

Programs 

At § 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 HHSapproved 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 § 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 × 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 × 

$40.94). 

D. Withdrawal of Approval of a PT 

Program 

At § 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 § 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. 


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13https://www.aha.org/statistics/fast-facts-ushospitals. 

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 


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TABLE 2: Summary of All Burden in This Final Rule 

Burden Hours 

Information Collection Requests Increase/Decrease(+/-)* Cost(+/-)* 

A. Clarification for Reporting of Microbiology Organism 

Identification +341 +18,660 

B. Optional On-Site Visits to PT Programs +0 +0 

C. PT Program Reapproval +90 +3,685 

D. Withdrawal of Annroval of a PT Program +0 +0 

TOTAL +431 +22,345 
41220 Federal Register / Vol. 87, No. 131 / Monday, July 11, 2022 / Rules and Regulations 

14CMS Clinical Laboratory Fee Schedule Files: 

https://www.cms.gov/Medicare/Medicare-Fee-forService-Payment/ClinicalLabFeeSched/ClinicalLaboratory-Fee-Schedule-Files. 

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. 

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 nonmicrobiology 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 CLIAapproved PT programs annually. We 

estimated material costs for purchasing 

PT materials based on the range of 2020 

catalog prices from the eight CLIAapproved 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. 

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 


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CLIA at § 493.801(a)(2)(ii) and 

§ 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 CLIAapproved accreditation organizations, 

data were provided by COLA showing 

how many of the 6,999 COLAaccredited 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 


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41222 Federal Register / Vol. 87, No. 131 / Monday, July 11, 2022 / Rules and Regulations 

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 §§ 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 


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khammond on DSKJM1Z7X2PROD with RULES2ER11JY22.002</GPH> ER11JY22.003</GPH>

Regulatory 

Change 

Gram Stain 

including 

Morphology 

Bacterial Toxin 

Detection 

Antimicrobial 

susceptibility 

testing 

Direct fungal 

antigen detection 

Detection of the 

presence of 

absence of fungi 

and aerobic 

actinomycetes 

without 

identification 

Direct parasite 

antigen detection 

TABLE 3: Low Estimate for Microbiolo!!V PT Re2ulatorv Chan2es 

Total Number 

of Affected Ml 

Laboratories 

31 

0 

4,299 

0 

0 

0 

Total Number 

of Affected M2 

Laboratories 

0 

546 

0 

37 

92 

336 

Labor' 

$4.27 

$16.00 

$23.62 

$12.61 

$7.71 

$12.90 

Supply/Material 

Cost2 

$4.53 

$12.80 

$12.00 

$16.80 

$16.20 

$11.20 

TOTAL Low 

Estimate for One 

Challenge 

$272.80 

$15,724.80 

$153,130.38 

$1,088.17 

$2,199.72 

$8,097.60 

'Average national CMS clinical laboratory fee schedule (https://www.cms.gov/Medicare/Medicare-Fee-for-ServicePayrnent/ClinicalLabF eeSched/Clinical-Laboratory-Fee-Schedule-Files). 

2Low 2020 PT catalog price per challenge. 

TABLE 4 : ff 12 h E s t" 1ma t e i or M" 1cro b. 10 I 02Y PTR e2u I a t ory Ch an2es 

Regulatory Total Number Total Number Supply/Ma TOTAL High TOTAL High 

Change of Affected Ml of Affected M2 Labor' terial Cost2 Estimate /for Estimate/for 15 

Laboratories Laboratories one challenge challenges 

Gram Stain 

including 31 0 $4.27 $15.40 $609.77 $9,146.55 

Morohologv 

Bacterial Toxin 0 546 $16.00 $83.00 $54,054.00 $810,810.00 Detection 

Antimicrobial 

susceptibility 4,299 0 $23.62 $31.80 $238,250.58 NIA 

testing 

Direct fungal 0 37 $12.61 $33.40 $1,702.37 $25,535.55 antigen detection 

Detection of the 

presence or 

absence of fungi 

and aerobic 0 92 $7.71 $18.67 $2,426.96 $36,404.40 

actinomycetes 

without 

identification 

Direct parasite 0 336 $12.90 $78.00 $30,542.40 $458,136.00 antigen detection 

1 Average national CMS clinical laboratory fee schedule (https://www.cms.gov/Medicare/Medicare-Fee-for-ServicePayment/ClinicalLabF eeSched/Clinical-Laboratory-Fee-Schedule-Files). 

2High 2020 PT catalog price per challenge. 

Total Low 

Estimate for 

Microbiology 

Regulatory 

Changes 

$180,513.47 

Total High 

Estimate 

for 

Microbiolo 

gy 

Regulatory 

Changes 

$1,340,032. 

50 
41224 Federal Register / Vol. 87, No. 131 / Monday, July 11, 2022 / Rules and Regulations 

BILLING CODE 4120–01–C 

b. Costs of PT Changes to the NonMicrobiology 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 

§§ 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 CLIArequired 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 × 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 CAPaccredited 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 


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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 CAPaccredited 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 CAPaccredited 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-CAPaccredited 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 CAPaccredited laboratories enrolled in CAP 

PT from the total number of CAPaccredited laboratories. 

We derived a low estimate of the total 

number of laboratories not accredited by 

CAP and not enrolled in one of the nonCAP 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 nonCAP 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 onetime costs for CoC and CoA laboratories 

will range from $13,497,696 to 

$26,995,392 ($93.82 × 35,967 × 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. 


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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 nonCAP accredited laboratories, and the 

fact that they tend not to enroll in nonrequired PT as frequently as CAPaccredited 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 

Table 6 shows the total estimated 

range of annual cost for the changes 

(including both microbiology and nonmicrobiology) 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. 


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TABLE 5: Low and High Estimates for Non-microbiology PT Regulations Changes 

Category Low Estimate High Estimate 

1. Laboratories accredited by CAP that $4,498,535.16 $4,498,535.16 purchase material from the CAP PT program 

2. Laboratories accredited by CAP that 

purchase PT materials from other PT $0.00 $1,304,342.82 

programs 

3. Laboratories not accredited by CAP that 

are not already enrolled in other PT $7,047,879.53 $58,710,509.52 

programs 

4. Laboratories not accredited by CAP $1,051,614.08 $1,051,614.08 that are enrolled in other PT programs 

Total increased cost $12,598,028.77 $65,565,001.58 

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TABLE 6: Total Estimated Annual Costs of PT Regulations Changes (All specialties in both m

, 

Undiscounted (2020 $) Discounted at 3 percent 

Primary Low# High& Primary Low 

2020 $60,141,226 $26,323,389 $93,959,062 $56,688,874 $24,812,319 

2021 $60,141,226 $26,323,389 $93,959,062 $55,037,742 $24,089,630 

2022 $60,141,226 $26,323,389 $93,959,062 $53,434,701 $23,387,991 

2023 $60,141,226 $26,323,389 $93,959,062 $51,878,350 $22,706,787 

2024 $60,141,226 $26,323,389 $93,959,062 $50,367,330 $22,045,424 

# Total low cost is the sum of Table 3 (microbiology), Table 4 (non-microbiology). 

& Total high cost is the sum of Table 3 (microbiology), Table 4 (non-microbiology). 

Discounted at 7 per

High Primary Lo

$88,565,429 $52,529,677 $$85,985,853 $49,093,156 $$83,481,411 $45,881,454 $$81,049,914 $42,879,863 $$78,689,237 $40,074,639 $
41228 Federal Register / Vol. 87, No. 131 / Monday, July 11, 2022 / Rules and Regulations 

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 CLIAapproved 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 


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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 


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TABLE7: A tin2 Stat t 

Category Primary Estimate Minimum Estimate Maximum Estimate 

BENEFITS 

Monetized benefits NA NA NA 

Annualized qualified, but More effective detection of NA NA 

Unmonetized, benefits laboratories that provide 

inaccurate laboratory test 

results. 

Increased confidence in 

laboratory test results. 

(Unqualified benefits) NA NA NA 

COSTS 

Annualized monetized costs $60,141,226 $26,323,389 $93,959,062 

Annualized qualified, but NA NA NA 

Unmonetized, benefits 

Qualitative (unquantified) costs NA NA NA 

TRANSFERS 

Annualized monetized transfers: "on NA NA NA 

budget" 

From whom to whom? NA NA NA 

Annualized monetized transfers: NA NA NA 

"off-budget" 

From whom to whom? NA NA NA 

Category Effects 

Effects on State, local, and/or tribal NA NA NA 

governments 

Effects on small businesses NA NA NA 

Effects on wages NA NA NA Effects on growth NA NA NA 
Federal Register / Vol. 87, No. 131 / Monday, July 11, 2022 / Rules and Regulations 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 endusers 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 


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41232 Federal Register / Vol. 87, No. 131 / Monday, July 11, 2022 / Rules and Regulations 

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 

§ 493.901(c)(8), previously proposed at 

§ 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 nonprofit 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 

■ 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). 

■ 2. Amend § 493.2 by— 

■ a. Adding the definitions of 

‘‘Acceptance limit’’ and ‘‘Peer group’’ in 

alphabetical order; and 

■ b. Revising the definition of ‘‘Target 

value’’. 

The additions and revision read as 

follows: 

§ 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. 

* * * * * 

■ 3. Amend § 493.20 by revising 

paragraph (c) to read as follows: 

§ 493.20 Laboratories performing tests of 

moderate complexity. 

* * * * * 

(c) If the laboratory also performs 

waived tests, compliance with 

§ 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 §§ 493.15(e), 

493.801(b)(1) through (6), 493.1771, 

493.1773, and 493.1775 

■ 4. Amend § 493.25 by revising 

paragraph (d) to read as follows: 

§ 493.25 Laboratories performing tests of 

high complexity. 

* * * * * 

(d) If the laboratory also performs 

waived tests, compliance with 

§§ 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 §§ 493.15(e), 

493.801(b)(1) through (6), 493.1771, 

493.1773, and 493.1775. 

■ 5. Amend § 493.801 by— 

■ a. Redesignating paragraphs (b)(3) 

through (6) as paragraphs (b)(4) through 

(7), respectively; and 

■ b. Adding new paragraph (b)(3). 

The addition reads as follows: 

§ 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. 

* * * * * 

■ 6. Amend § 493.861 by revising 

paragraph (a) to read as follows: 

§ 493.861 Standard; Unexpected antibody 

detection. 

(a) Failure to attain an overall testing 

event score of at least 100 percent is 

unsatisfactory performance. 

* * * * * 

■ 7. Amend § 493.901 by— 

■ a. Redesignating paragraphs (a), (b), 

(c), and (d) as paragraphs (b), (c), (d), 

and (e), respectively; 

■ b. Adding new paragraph (a); 

■ c. In newly redesignated paragraph 

(c)(7) by removing ‘‘;’’ and adding in its 

place ‘‘; and’’; 

■ d. Adding new paragraph (c)(8); 

■ e. Revising newly redesignated 

paragraph (e); and 

■ f. Adding new paragraph (f). 

The additions and revisions read as 

follows: 

§ 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 § 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 


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periodically or when problems are 

encountered for previously HHSapproved 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. 

■ 8. Amend § 493.903 by— 

■ a. In paragraph (a)(1) by removing the 

period and adding ‘‘;’’; 

■ b. In paragraph (a)(2) by removing ‘‘;’’ 

and adding in its place ‘‘; and’’; and 

■ c. By adding new paragraph (a)(3). 

The addition reads as follows: 

§ 493.903 Administrative responsibilities. 

* * * * * 

(a) * * * 

(3) Not change submitted laboratory 

data and results for any proficiency 

testing event; 

* * * * * 

■ 9. Section 493.905 is revised to read 

as follows: 

§ 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 §§ 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 

§§ 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. 

■ 10. Section 493.911 is revised to read 

as follows: 

§ 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 immunocompromised 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. 


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(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) × 

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 × 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. 

■ 11. Section 493.913 is revised to read 

as follows: 

§ 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 acidfast 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 


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Federal Register / Vol. 87, No. 131 / Monday, July 11, 2022 / Rules and Regulations 41235 

reportable, the sample grade would be 

1/(1+1) × 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. 

■ 12. Section 493.915 is revised to read 

as follows: 

§ 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) × 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. 

■ 13. Section 493.917 is revised to read 

as follows: 

§ 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. 


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41236 Federal Register / Vol. 87, No. 131 / Monday, July 11, 2022 / Rules and Regulations 

(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) × 

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. 

■ 14. Section 493.919 is revised to read 

as follows: 

§ 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) × 

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. 

■ 15. Amend § 493.923 by revising 

paragraphs (a) and (b)(1) to read as 

follows: 

§ 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 


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Federal Register / Vol. 87, No. 131 / Monday, July 11, 2022 / Rules and Regulations 41237 

percent or more of all participating 

laboratories. Both methods must be 

attempted before the program can 

choose to not grade a PT sample. 

* * * * * 

■ 16. Amend § 493.927 by revising 

paragraphs (a), (b), (c)(1), and (2) to read 

as follows: 

§ 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 (HIV) ........................ Reactive (positive) or nonreactive (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. 


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41238 Federal Register / Vol. 87, No. 131 / Monday, July 11, 2022 / Rules and Regulations 

* * * * * 

■ 17. Amend § 493.931 by revising 

paragraphs (a), (b), (c)(1) and (2) to read 

as follows: 

§ 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/SGPT) ............................. Target value ±15% or ±6 U/L (greater). 

Albumin .............................................................................. Target value ±8%. 

Alkaline phosphatase ......................................................... Target value ±20%. 

Amylase .............................................................................. Target value ±20%. 

Aspartate aminotransferase (AST/SGOT) ......................... Target value ±15% or ±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). 


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Federal Register / Vol. 87, No. 131 / Monday, July 11, 2022 / Rules and Regulations 41239 

TABLE 2 TO PARAGRAPH (C)(2)—CRITERIA FOR ACCEPTABLE PERFORMANCE—Continued 

The criteria for acceptable performance are— 

Analyte or test Criteria for acceptable performance 

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 lipoprotein (HDL) ....................... Target value ±20% or ±6 mg/dL (greater). 

Cholesterol, low density lipoprotein (LDL), direct measurement.Target value ±20%. 

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 devices cleared by 

FDA for home use.).

Target value ±8% or ±6 mg/dL (greater). 

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 (TIBC). (direct measurement) Target value ±20%. 

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%. 

* * * * * 

■ 18. Amend § 493.933 by revising 

paragraphs (a), (b), (c)(1), and (2) to read 

as follows: 

§ 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 


khammond on DSKJM1Z7X2PROD with RULES2
41240 Federal Register / Vol. 87, No. 131 / Monday, July 11, 2022 / Rules and Regulations 

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 pregnancy tests done by 

visual color comparison categorized as waived tests).

mIU/mL (greater) or positive or negative. 

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). 

* * * * * 

■ 19. Amend § 493.937 by revising 

paragraphs (a), (b), (c)(1), and (2) to read 

as follows: 

§ 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. 


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

* * * * * 

■ 20. Amend § 493.941 by revising 

paragraphs (a), (b), (c)(1) and (2) to read 

as follows: 

§ 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 hematocrit) ............................ Target ±4%. 

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. 


khammond on DSKJM1Z7X2PROD with RULES2
41242 Federal Register / Vol. 87, No. 131 / Monday, July 11, 2022 / Rules and Regulations 

TABLE 2 TO PARAGRAPH (c)(2)—CRITERIA FOR ACCEPTABLE PERFORMANCE—Continued 

The criteria for acceptable performance are: 

Analyte or test Criteria for acceptable performance 

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

* * * * * 

■ 21. Amend § 493.959 by revising 

paragraphs (b), (d)(1) and (2) to read as 

follows: 

§ 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 


khammond on DSKJM1Z7X2PROD with RULES2