1536 Federal Register / Vol. 84, No. 23 / Monday, February 4, 2019 / Proposed Rules 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Centers for Medicare & Medicaid 

Services 

42 CFR Part 493 

[CMS–3355–P] 

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: Proposed rule. 

SUMMARY: This proposed rule would 

update 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 proposed rule would 

also make additional technical changes 

to PT referral regulations to more 

closely align them with the CLIA 

statute. 

DATES: To be assured consideration, 

comments must be received at one of 

the addresses provided below, no later 

than 5 p.m. on April 5, 2019. 

ADDRESSES: In commenting, please refer 

to file code CMS–3355–P. Because of 

staff and resource limitations, we cannot 

accept comments by facsimile (FAX) 

transmission. 

Comments, including mass comment 

submissions, must be submitted in one 

of the following three ways (please 

choose only one of the ways listed): 

1. Electronically. You may submit 

electronic comments on this regulation 

to http://www.regulations.gov. Follow 

the ‘‘Submit a comment’’ instructions. 

2. By regular mail. You may mail 

written comments to the following 

address ONLY: Centers for Medicare & 

Medicaid Services, Department of 

Health and Human Services, Attention: 

CMS–3355–P, P.O. Box 8016, Baltimore, 

MD 21244–8016. 

Please allow sufficient time for mailed 

comments to be received before the 

close of the comment period. 

3. By express or overnight mail. You 

may send written comments to the 

following address ONLY: Centers for 

Medicare & Medicaid Services, 

Department of Health and Human 

Services, Attention: CMS–3355–P, Mail 

Stop C4–26–05, 7500 Security 

Boulevard, Baltimore, MD 21244–1850. 

For information on viewing public 

comments, see the beginning of the 

SUPPLEMENTARY INFORMATION section. 

FOR FURTHER INFORMATION CONTACT: 

Sarah Bennett, CMS, (410) 786–3531; 

Caecilia Blondiaux, CMS, (410) 786– 

2190; or Nancy Anderson, CDC, (404) 

498–2741 

SUPPLEMENTARY INFORMATION: 

Inspection of Public Comments: All 

comments received before the close of 

the comment period are available for 

viewing by the public, including any 

personally identifiable or confidential 

business information that is included in 

a comment. We post all comments 

received before the close of the 

comment period on the following 

website as soon as possible after they 

have been received: http://

www.regulations.gov. Follow the search 

instructions on that website to view 

public comments. 

Table of Contents 

I. Background 

II. Provisions of the Proposed Regulations 

A. Proposed Changes for Microbiology PT 

B. Proposed Changes to PT for NonMicrobiology Specialties and 

Subspecialties 

C. Additional Proposed Changes 

III. Collection of Information Requirements 

IV. Response to Comments 

V. Regulatory Impact Analysis 

A. Statement of Need 

B. Overall Impact 

C. Anticipated Effects 

D. Alternatives Considered 

E. Accounting Statements and Table 

F. Regulatory Reform Analysis Under E.O. 

13771 

G. Conclusion 

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 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, among other 

things, for laboratories conducting 

moderate or high-complexity testing to 

enroll in an approved proficiency 

testing (PT) program for each specialty, 

subspecialty, and analyte or test for 

which the laboratory is certified under 

CLIA. PT referral was further addressed 

by enactment of the Taking Essential 

Steps for Testing Act of 2012 (Pub. L. 

112–202, December 4, 2012) (TEST Act) 

and our implementing regulations (79 

FR 25435 and 79 FR 27105). As of 

January 2017, there were 246,143 CLIAcertified laboratories, of which 36,777 

Certificate of Compliance and Certificate 

of Accreditation 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. 

Testing has evolved significantly 

since 1992, and technology is now more 

accurate and precise than the methods 

in use at the time the PT regulations 

became effective for all laboratories 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 cardiac markers, 

such as troponins, 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 are proposing revisions to 

our existing PT regulations in this 

proposed rule. 

As part of the process for developing 

our proposals to revise the PT 

regulations, HHS requested input from 

the Clinical Laboratory Improvement 

Advisory Committee (CLIAC) regarding 

appropriate revisions to the regulations. 

CLIAC is the official federal advisory 

committee charged with advising HHS 

regarding appropriate regulatory 

standards for ensuring accuracy, 

reliability and timeliness of laboratory 

testing. Questions posed to CLIAC at the 

September 2008 CLIAC meeting and 

their recommendations are documented 

in the meeting summary on the CLIAC 

website at https://ftp.cdc.gov/pub/ 

CLIAC_meeting_presentations/pdf/ 

CLIAC_Summary/cliac0908_

summary.pdf. 

In response to our request for input, 

CLIAC established a PT Workgroup that 

included laboratory experts, 

representatives from accreditation 

organizations, state surveyors, and PT 

program officials. The CLIAC PT 

Workgroup provided information and 

data to CLIAC for their deliberation in 

making recommendations to HHS 

regarding appropriate revisions to 

subparts H and I of the CLIA 

regulations. These recommendations 

addressed updating the list of required 

PT analytes; revising the scoring criteria 

for acceptable performance for current 

and proposed analytes; changes to 

specialties or subspecialties, including 

microbiology, that do not have required 


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PT analytes; and clarification of the PT 

referral requirements. The questions 

posed to CLIAC at the September 2010 

CLIAC meeting and their 

recommendations are documented in 

the meeting summary on the CLIAC 

website at http://wwwn.cdc.gov/cliac/ 

pdf/cliac0910.pdf. 

After the September 2010 CLIAC 

meeting, CMS and CDC met to review 

and consider the recommendations. 

Following this, the two agencies 

collaborated to develop a process to 

revise the list of required PT analytes. 

That is, CMS and CDC reviewed current 

analytes listed in subpart I to determine 

which analytes should be retained in 

the regulations and which should be 

deleted. In addition, CMS and CDC 

examined analytes not currently listed 

in subpart I to determine if any 

additional analytes should be added to 

subpart I. 

As discussed in section II of this 

proposed rule, a systematic approach 

was taken in order to update the 

required PT analytes, using various 

factors in selecting candidate analytes. 

A variety of PT-related and test volume 

data were subsequently collected from 

HHS-approved PT programs and various 

sources as described below, and 

analyzed by CMS and CDC. 

As discussed in section II.B.2. of this 

proposed rule, CMS and CDC used those 

data and applied the criteria in a stepwise approach to determine the analytes 

included in this proposed rule. 

Following selection of those candidate 

analytes, 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; 

mechanism for grading current of 

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 candidate analytes 

and the replacement of the list of 

specific organisms for each 

microbiology subspecialty at the above 

citations with our proposal to adopt a 

general list of types of microorganisms 

for each microbiology subspecialty. 

Specifically, with CDC’s expertise and 

assistance, we then developed an 

approach and rationale, as discussed in 

section II.B.10. of this proposed rule, for 

revising PT acceptance limits based 

upon empirical data, including clinical 

relevance. CMS and CDC worked to 

determine the acceptance limits, that is, 

the symmetrical tolerance (plus and 

minus) around the target value (as 

defined in § 493.2), to propose for both 

new and existing required analytes. As 

a result of this work, we ultimately 

decided to propose stating acceptance 

limits as percentages whenever possible. 

We then again sought industry input. 

For each analyte, we requested that PT 

programs consider our potential new 

acceptance limits and provide data 

simulations using real PT data as a 

means of pilot testing our potential 

acceptance limits. We received 

simulation data from several PT 

programs, which facilitated the 

development of the acceptance limits 

proposed in this rule. We note that 

acceptance limits 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 

This section provides an overview of 

our proposed revisions to the CLIA 

definitions and PT 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. 

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. 

Based on input from the PT Workgroup, 

CLIAC suggested revision of the 

regulations to include broad categories 

for the types of PT required for each 

microbiology subspecialty to allow 

flexibility for 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 to microbiology subspecialties in 

future rulemaking. Based on these 

recommendations and our review, we 

are proposing 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 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 are proposing 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 one of the 

following: 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 493.913(a): For 

mycobacteriology, we are proposing 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 


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antimycobacterial susceptibility or 

resistance testing. 

• Section 493.915(a): For mycology, 

we are proposing that the categories for 

which PT is required include, as 

applicable: Direct fungal antigen 

detection; detection and identification 

of fungi and aerobic actinomycetes 

which includes 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 493.917(a): For 

parasitology, we are proposing that the 

categories for which PT is required 

include, as applicable: Direct parasite 

antigen detection; and detection and 

identification of parasites which 

includes one of the following— 

detection of the presence or absence of 

parasites or identification of parasites. 

• Section 493.919(a): For virology, we 

are proposing that the categories for 

which PT is required include, as 

applicable: Viral antigen detection; 

detection and identification of viruses; 

and antiviral susceptibility or resistance 

testing. 

In all of these subspecialties, as 

outlined in sections II.B.5., II.B.7., and 

II.B.8. of this proposed rule, we are also 

proposing to revise the requirements for 

evaluation of a laboratory’s performance 

at §§ 493.911(b) through 493.919(b) to 

be consistent with these categories. 

We are not proposing to include 

antigen and toxin detection in the 

mycobacteriology subspecialty because 

no PT program currently offers 

applicable PT modules. We are not 

proposing to include stains and 

antiparasitic susceptibility or resistance 

testing in the subspecialty of 

parasitology because no PT program 

offers applicable PT modules. We invite 

the public to comment on these 

proposals and specifically on the 

proposed categories of testing for the 

subspecialties listed above. If public 

comments indicate that applicable PT 

modules are available for antigen and 

toxin detection or for stains and 

antiparasitic susceptibility or resistance 

testing, we may finalize their inclusion 

in the final rule, as applicable. If at 

some point in the future, PT becomes 

available 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. 

2. Major Groups of Microorganisms 

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 assure 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 of the current regulatory list. By 

restructuring to a more general list of 

organisms, it will be clearer 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 are 

proposing 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. 

• § 493.911(a)(3): For bacteriology, we 

are proposing 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; grampositive bacilli; gram-negative cocci; 

and gram-positive cocci. The more 

general list of types of organisms will 

continue to cover the six major groups 

of bacteria currently listed in the 

regulations. 

• § 493.913(a)(3): For 

mycobacteriology, we are proposing that 

the annual program content must 

include Mycobacterium tuberculosis 

complex and Mycobacterium other than 

tuberculosis (MOTT), if appropriate for 

the sample sources. 

• § 493.915(a)(3): For mycology, we 

are proposing 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. 

• § 493.917(a)(3): For parasitology, we 

are proposing that the annual program 

content must include intestinal 

parasites and blood and tissue parasites, 

if appropriate for the sample sources. 

• § 493.919(a)(3): For virology, we are 

proposing that the annual program 

content must include respiratory 

viruses, herpes viruses, enterovirus, and 

intestinal viruses, if appropriate for the 

sample sources. 

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 that would be 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 it is the 

inspecting agency’s responsibility to 

review and take 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 are 

proposing 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. 

4. Gram Stain PT 

CLIAC considered whether required 

PT for Gram stains should include both 

stain reaction and morphology. CLIAC 

concluded it should and recommended: 


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• 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 are proposing 

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. 

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. The purpose of this 

requirement is 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, but 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 are proposing changes as 

follows: 

• Section 493.911(a)(2): In 

bacteriology, we are proposing 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 are 

proposing 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 do not propose to make 

any changes to these subspecialties. 

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 detection of 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 

are proposing the following: 

• Section 493.911(a)(4): For 

bacteriology, we are proposing to 

require 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 are proposing to 

require 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 are proposing to require 

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 are proposing to require at least two 

PT samples per event for susceptibility 

or resistance testing, including viruses 

that have a predetermined pattern of 


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1Office of Management and Budget control 

number 0920–0961. Expiration date 4/30/2015. 

2Earley, Marie C., J. Rex Astles, and Karen 

Breckenridge. Practices and Perceived Value of 

Proficiency Testing in Clinical Laboratories. Journal 

of Applied Laboratory Medicine 1, 4 (2017), pp. 

415–420. 

susceptibility or resistance to common 

antiviral agents. 

In each of these subspecialties, we are 

also proposing to revise the 

requirements for 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 testing and 

that the scoring should be consistent 

with the testing performed. 

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 

there are a number of modules that 

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 are 

proposing: 

• To retain the requirement for direct 

antigen detection for: 

++ Section 493.911(a)(1)(ii): 

Bacteriology. 

++ Section 493.919(a)(1)(i): Virology. 

And add the requirement for direct 

antigen testing detection for: 

++ Section 493.915(a)(1)(i): 

Mycology. 

++ Section 493.917(a)(1)(i): 

Parasitology. 

• To require PT for bacterial toxin 

detection under § 493.911(a)(1)(iii). No 

changes are proposed for 

mycobacteriology. 

• To 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). 

B. Proposed Changes to PT for NonMicrobiology Specialties and 

Subspecialties 

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. Considering CLIAC’s 

recommendations regarding possible 

changes to the analytes for which PT is 

required, 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 it is not necessary to 

require PT for every analyte to derive 

benefits generalizable to all test 

methods. 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 1 conducted by 

CDC and the Association of Public 

Health Laboratories (APHL) in 2013, a 

large number of laboratories voluntarily 

purchased PT materials for many 

nonrequired analytes.2 Keeping this in 

mind, as discussed in section II.B.2. of 

this proposed rule, we are proposing to 

add 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 

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 eleven existing PT programs. 

We determined that limiting the 


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3https://meps.ahrq.gov/mepstrends/hc_ins/. 

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). Expected impact on 

laboratories and PT programs was also 

taken into account (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 that are 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 that were below the 

500,000 threshold that we determined to 

be clinically important based on 

literature already footnoted in section 

II.B.2.b. of this 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 this 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 

reimbursements, as well as the most 

current MarketScan Commercial Claims 

and Encounters (CCAE) and MarketScan 

Medicaid Multi-state data sets (2009 

Truven Health MarketScan® data, 

https://truvenhealth.com/yourhealthcare-focus/life-sciences/data_

databases_and_online_toolsMarkets/ 

Life-Sciences/Products/Data-Tools/ 

MarketScan-Databases) 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 tests we 

considered for addition to, or deletion 

from, subpart I in order 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 in order to evaluate 

the trends in performing testing for the 

proposed analytes. We analyzed 

national trends in testing based upon 

Medicare Part B reimbursement data 

(https://www.ncbi.nlm.nih.gov/pmc/ 

articles/PMC4698806/) 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 

reimbursement for the proposed 

analytes. 

We estimated the 2009 national test 

volumes based upon two data sets: (1) 

Medicare Part B reimbursement 

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 for this 

sector no estimation of total counts was 

necessary. MarketScan data, which is 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 of these 

categories for the entire United States. 

The Agency for Healthcare Research and 

Quality (AHRQ) 3 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 U.S. 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 

numbers of tests being performed 

annually per analyte. No other accurate 

data were available to us. 

As noted above, for the second cut, 

based upon our estimates of national 

testing volumes, we decided that an 

estimated national test volume of 

500,000 per analyte annually was an 

appropriate threshold as most of the 

analytes listed in subpart I had national 

testing volumes above this threshold. 

Together with the above-described 

analytes that were 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 as to patient and 

public impact for each analyte. There 

was no standardized, generally accepted 

way available to us to assess the relative 

impact of testing for particular analytes 

on clinical care and public health. 

Therefore, we used the following 

parameters 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) 

(http://www.accessdata.fda.gov/scripts/ 

cdrh/cfdocs/cfClia/Search.cfm). We 

accessed several data sources, including 

tests listed in the CDC Guide to 

Community Preventive Services 


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4AHRQ’s National Guideline Clearinghouse 

website accessed for this proposed rule, however, 

no longer exists on the internet effective July 16, 

2018. 

5Burtis, C. A., Ashwood, E. R., & Bruns, D. E. 

(2012). Tietz Textbook of Clinical Chemistry and 

Molecular Diagnostics. London: Elsevier Health 

Sciences. 

6Laboratory critical values policies and 

procedures: a college of American Pathologists QProbes Study in 623 institutions. Howanitz PJ, 

Steindel SJ, Heard NV. Arch Pathol Lab Med. 2002 

Jun;126(6):663–9. 

7Barry, Micheael J. Screening for Prostate 

Cancer—The Controversy That Refuses to Die. New 

England Journal of Medicine 360;13 (March 2009). 

8Eck, Leigh M. Should family physicians screen 

for vitamin D deficiency? yes: targeted screening in 

at-risk populations is prudent. American Family 

Physician 87, 8 (2013), pp. 541b.Fr. 

9 Kopes-Kerr, Colin. Should family physicians 

screen for vitamin D deficiency? no: screening is 

unnecessary, and routine supplementation makes 

more sense. American Family Physician 87, 8 

(2013), pp. 540b. 

10Wagar, Friedberg, Souers, and Stankovic, 2007, 

https://www.ncbi.nlm.nih.gov/pubmed/18081434. 

11www.mayomedicallaboratories.com/testcatalog/appendix/criticalvalues/index.html. 

(https://www.thecommunityguide.org); 

National Healthcare Priorities/ 

Disparities reports (https://

www.ahrq.gov/research/findings/ 

nhqrdr/index.html); clinical practice 

guidelines including the National 

Guideline Clearinghouse (NGC) 

database available from AHRQ (https:// 

www.guideline.gov/); 4 critical values 

available in publications; 5 and (CAP) QProbes.6

In order to assess patient and public 

impact for each analyte, we considered 

the evidence available related to each 

analyte under consideration. To do so, 

our first parameter was a review of 

published LPGs. We hypothesized that 

if there was 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).789

Our second parameter was a review of 

critical values. Critical values are predetermined limits for specific analytes 

that when exceeded may suggest that 

immediate clinical intervention is 

required. We assessed analytes included 

on ‘‘critical values’’ lists to determine 

the analyte’s relative importance in 

helping clinicians to make rapid lifealtering decisions. This approach 

allowed us to gauge how important an 

accurate result could be because an 

incorrect result could lead to a lifethreatening intervention or a failure to 

intervene. We reviewed published 

literature 10 and critical values posted 

online from 16 institutions including 

small hospitals, university hospitals, 

and reference laboratories.11

Our final parameter for assessing the 

clinical impact of an analyte was 

reviewing its medical device 

classification (Class I, II, or III) as 

categorized by the Food and Drug 

Administration’s risk classification list. 

In a similar way, 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 (https://www.uspreventive

servicestaskforce.org/Page/Name/ 

recommendations), the National 

Healthcare Quality and Disparities 

Report (https://www.ahrq.gov/research/ 

findings/nhqrdr/index.html), the CDC 

Hormone Standardization Program 

(https://www.cdc.gov/labstandards/ 

hs.html). For some analytes that have 

important public health impact, such as 

blood lead, we consulted with subject 

matter experts in the CDC 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 

this proposed rule. 

Therefore, we used those parameters 

in an attempt to get a relative sense of 

the patient and public health impact of 

the analytes under consideration, but, 

using the data available to us, we found 

no standardized, generally accepted way 

to assess the relative impact of testing 

for particular analytes on clinical care 

and public health. 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 upon 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 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 above, 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). 

TABLE 1—ANALYTES PROPOSED FOR

ADDITION TO SUBPART I 

CLIA 

Regulation Analytes 

General Immunology, 

§ 493.927.

Anti-HBs, Anti-HCV, C-reactive protein (high sensitivity). 


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12Shahangian, Alspach, Astles, Yesupriya, and 

Dettwyler, 2014, https://www.ncbi.nlm.nih.gov/ 

pmc/articles/PMC4698806/. 

13 Krumholz, et al, 2015) (NICE, 2012, https://

www.nice.org.uk/guidance/cg137). 

14Shahangian, Alspach, Astles, Yesupriya, and 

Dettwyler, 2014 https://www.ncbi.nlm.nih.gov/ 

pmc/articles/PMC4698806/. 

TABLE 1—ANALYTES PROPOSED FOR

ADDITION TO SUBPART I—Continued 

CLIA 

Regulation Analytes 

Routine Chemistry, 

§ 493.931.

B-natriuretic peptide (BNP), 

ProBNP, Cancer antigen 

(CA) 125, Carbon dioxide, 

Carcinoembryonic antigen, 

Cholesterol, low density 

lipoprotein, Ferritin, 

Gamma glutamyl transferase, Hemoglobin A1c, 

Phosphorus, Prostate specific antigen, total, Total 

iron binding capacity, 

Troponin I, Troponin T. 

Endocrinology, 

§ 493.933.

Estradiol, Folate, serum, Follicle stimulating hormone, 

Luteinizing hormone, Progesterone, Prolactin, Parathyroid hormone, Testosterone, Vitamin B12. 

Toxicology, 

§ 493.937.

Acetaminophen, serum, Salicylate, Vancomycin. 

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 of the 

therapeutic drugs (ethosuximide, 

quinidine, primidone, and 

procainamide and its metabolite, Nacetyl procainamide). New drugs that 

are more effective or safer have entered 

the market since 1992, and may have 

replaced use of the 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 be a 

result of 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.12 For some of the 

anticonvulsant drugs, there may have 

been changes in medical practice, 

including alternative drugs and other 

treatments, possibly decreasing the need 

to measure them.13 We identified 13 

currently required analytes with 

national test volumes that were 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 14 and we attempted to project 

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 on 

clinical medicine and public health of 

deleting these analytes. 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 Be 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 above, we propose 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, Nacetyl 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 are 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 are available to 

indicate that such an evaluation is not 

appropriate. 

We recognize, based on input from PT 

programs, that peer grouping is 

generally the way that target values are 


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15Thompson, Michael. Variation of precision 

with concentration in an analytical system. Analyst, 

113, (1988), pp. 1579–1587. 

set for most analytes. Therefore, in this 

rule, we are proposing to continue 

allowing PT programs to use peer 

grouping to set the target values. In 

addition, we propose 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 

acceptance limits (AL) that were 

originally specified in each specialty 

and subspecialty of the CLIA’88 

regulations in subpart I effectively allow 

for a 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 that 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 believe it is 

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 standard 

deviation (SD) of results from the mean 

of other participants in the peer group; 

fixed limit as a percentage of the 

assigned value; fixed limit in 

concentration units; and a mixture of 

percentage and concentration units, 

depending on the concentration of the 

analyte. For all new and currently 

required non-microbiology analytes, we 

propose to use fixed ALs, preferably as 

percentage limits rather than 

concentration units. 

There are 53 analytes (existing or 

proposed) for which we are proposing a 

percentage-based AL, for which 

biological variability data were 

published. For several analytes (for 

example, therapeutic drugs) there were 

no biological variability data because 

these analytes do not occur naturally in 

the body. 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, and 

then we simulated several percentagebased 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 upon 

biological variability would be 

untenable because the current analytical 

accuracy for such testing would not be 

expected to be able 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 

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. In our opinion, 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 were able to 

successfully make 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 this proposed rule, we are proposing 

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 15. 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 more fair and realistic ALs, 

we propose 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 are proposing to amend 

certain analytes in §§ 493.927, 493.931, 

493.933, 493.937, 493.941 and 493.959 


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Federal Register / Vol. 84, No. 23 / Monday, February 4, 2019 / Proposed Rules 1545 

16Tonks, David B. A study of the accuracy and 

precision of clinical chemistry determinations in 

170 Canadian laboratories. Clinical Chemistry 9, 2 

(1963), pp. 217–233. 

17Cotlove, Ernest, Eugene K. Harris, and George 

Z. Williams. Biological and analytic components of 

variation in long-term studies of serum constituents 

in normal subjects. Clinical Chemistry 16, 12 

(1970), pp. 1028–1032. 

18Fraser, Callum. The 1999 Stockholm consensus 

conference on quality specifications in laboratory 

medicine. Clinical Chemistry and Laboratory 

Medicine 53, 6 (2015), pp. 837–840. 

19Burtis, Carl A., Edward R. Ashwood, David E. 

Bruns, Ed. Tietz textbook of clinical chemistry and 

molecular diagnostics. (Chapter 2 Selection and 

analytical evaluation of methods with statistical 

techniques, pp. 17), Elsevier Saunders, 

Philadelphia, P.A., (2012). 

20Burtis, Carl A., Edward R. Ashwood, David E. 

Bruns, Ed. Tietz textbook of clinical chemistry and 

molecular diagnostics. (Chapter 17 Preanalytic 

variables and biological variation, pp. 470–471), 

Elsevier Saunders, Philadelphia, P.A., (2006). 

21https://www.westgard.com/biodatabase1.htm. 

22Astles, Tholen, and Mitchell, 2016, https://

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

23Howerton, Krolak, Manasterski, and 

Handsfield, 2010. 

24Howerton D1, Krolak JM, Manasterski A, 

Handsfield JH. Arch Pathol Lab Med. 2010 

May;134(5):751–8. Proficiency testing performance 

in US laboratories: results reported to the Centers 

for Medicare & Medicaid Services, 1994 through 

2006. 

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 are proposing to 

change the ALs to percentages. Over the 

years, there have been many proposed 

criteria for establishing goals for 

analytical performance.16 17 The various 

possible approaches were reviewed and 

a hierarchy was established based upon 

a 1999 consensus conference.18 These 

strategies were reconsidered in 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.19

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, for 

monitoring progress, we believe the 

most important factor 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.20 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 

publically available estimates of 

allowed total error based upon estimates 

of biological variability 21 to 

approximate the proposed AL. CDC has 

shown in an a recent poster 22 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 are proposing 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 23 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 which were previously 

required to perform PT under CLIA’67. 

Howerton, et al.24 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, and 

this is consistent with CLIA’s intent to 

ensure accurate clinical testing 

regardless of the setting where testing is 

performed. There are several factors 

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 are 

proposing to make criteria for 

acceptable performance for existing 

analytes listed in subpart I tighter so 

they are in closer agreement with 

analytical accuracy goals which are 

based upon biological variability and 

simulation data. 

Therefore, based on the simulation 

data, we are proposing to tighten ALs 

for certain current analytes in 

§§ 493.927, 493.931, 493.933, 493.937, 

493.941 and 493.959. 

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 CMS and CDC 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 


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absolute concentrations in lieu of 

percentage ALs, as was described 

previously. We then requested narrowly 

tailored data from PT programs as 

described above 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 ALs 

proposed in this rule. 

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 are likely meeting 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 

modelled statistically. Finally, the 

distribution of unsatisfactory and 

unsuccessful PT scores is not randomly 

distributed across all participants. 

C. Additional Proposed Changes 

We are proposing to amend § 493.2 to 

modify the definition of an existing term 

and define new terms as follows: 

• Target value: We are removing the 

reference to NRSCL and NCCLS and 

retaining the other options for setting 

target values are retained in this 

proposed rule. 

• Acceptance Limit: We are proposing 

to define this term to mean the 

symmetrical tolerance (plus and minus) 

around the target value. 

• Unacceptable score: We are 

proposing to define this term to mean 

PT results that are outside the criteria 

for acceptable performance for a single 

challenge or sample. 

• Peer group: We are proposing to 

define 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 are also proposing the following 

revisions to the regulation text at 

subpart A: 

• Sections 493.20 and 493.25: We are 

proposing 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 propose 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 are also proposing the following 

revision to the regulation text at subpart 

H: 

• Section 493.861: We are 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 are proposing 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 are also proposing the following 

revisions to the regulation text at 

subpart I: 

• Section 493.901(a): We are 

proposing to require that each HHSapproved PT program have a minimum 

of ten laboratory participants before 

offering any PT analyte. We recognize 

that PT programs do not grade results 

when there are fewer than ten 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 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 are 

proposing 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 allow 

laboratories to only report PT results 

electronically with no other reporting 

option such as facsimile or mailed PT 

submission forms. However, at this 

time, the PT programs who 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 are 

proposing 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 are 

proposing to add the requirement that 

HHS may perform on-site visits for all 

initial PT program applications for HHS 

approval and periodically for previously 

HHS-approved PT programs either 

during the reapproval process or as 

necessary to review and verify the 


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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 are 

proposing to add an additional 

requirement to the regulation that 

specifies CMS 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 

are proposing to add 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 are proposing 

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 are also proposing to 

add a requirement that the PT program 

may request reconsideration should 

CMS determine that false or misleading 

information was provided of if the PT 

program has failed to correct issues 

identified by HHS related to PT program 

requirements. 

• Sections 493.911 through 493.919: 

We are proposing, as discussed in 

section II.A.1. of this proposed rule, to 

modify the regulation by removing the 

types of services listed for each 

microbiology subspecialty. We are also 

proposing to remove specific lists of 

example organisms from each 

microbiology subspecialty and replace 

the list with broader categories of 

organisms. 

• Section 493.911(a): For 

bacteriology, as discussed in sections 

II.A.1. and V.C. of this proposed rule, 

we are proposing that the categories 

required include Gram stain including 

bacterial morphology; direct bacterial 

antigen detection; bacterial toxin 

detection; detection and identification 

of bacteria; and antimicrobial 

susceptibility or resistance testing on 

select bacteria. 

• Section 493.911(a)(3): We are 

proposing 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): We are 

proposing to include required PT for 

acid-fast stain; detection and 

identification of mycobacteria; and 

antimycobacterial susceptibility or 

resistance testing. 

• Section 493.913(a)(3): For 

mycobacteriology, we are proposing 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 are proposing to require PT for direct 

fungal antigen detection; detection and 

identification of fungi and aerobic 

actinomycetes; and antifungal 

susceptibility or resistance testing. 

• Section 915(a)(3): We are we are 

proposing 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 are proposing to 

require PT for direct parasite antigen 

detection and detection and 

identification of parasites. 

• Section 493.917(a)(3): We are 

proposing 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 

are proposing to require PT for viral 

antigen detection; detection and 

identification of viruses to the highest 

level that the laboratory reports results 

on patient specimens; and antiviral 

susceptibility or resistance testing. 

• Section 493.919(a)(3): We are 

proposing that the annual program 

content must include respiratory 

viruses, herpes viruses, enterovirus, and 

intestinal viruses, if appropriate for the 

sample source. 

• Sections 493.911(b)(1), 

493.913(b)(1), 493.915(b)(1), 

493.917(b)(1), 493.919(b)(1), 

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 are proposing to 

amend these provisions 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 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. 

• Sections 493.923(a), 493.927(a), 

493.931(a), 493.933(a), 493.937(a), 

493.941(a), and 493.959(b): We are 

proposing 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 are proposing 

to amend, as discussed in sections II.B.8 

through II.B.10. of this proposed rule, 

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 are adding ALs 

based on percentages or target values in 

addition to retaining the qualitative 

target values. We propose to make this 

allowance in CLIA for reporting PT 

which reflects current practice. 

• Section 493.931(b): We are 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, for example 

using an immunoassay. 

• Section 493.933: We propose to add 

the following analytes: Estradiol, folate 

(serum), follicle stimulating hormone, 

luteinizing hormone, progesterone, 

prolactin, parathyroid hormone, 

testosterone, and vitamin B12. 

• Section 493.937(a): We are 

proposing to revise 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 are 

proposing 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 are 

differentiating the criteria for units of 

reporting of the analyte prothrombin 

time. Currently the analyte prothrombin 

time can be reported in seconds and/or 


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INR (international normalized ratio), so 

we are proposing to amend the criteria 

for acceptable performance to reflect 

both units of reporting and proposing to 

add the requirement that laboratories 

must report prothrombin time for PT the 

same way they report it for patient 

results; if patient results are reported in 

seconds or as INR results, they should 

report the same way to PT programs. If 

the laboratory reports patient results 

both in seconds and as INR, they should 

be reported the same way to the PT 

programs. We are also proposing to add 

criteria for acceptable performance for 

directly measured INR for prothrombin 

time. In addition, we propose to require 

laboratories that perform both cell 

counts and differentials to conduct PT 

for both (that is, the ‘‘or’’ would be 

changed to an ‘‘and’’). Finally, we are 

proposing to change the criteria for 

acceptable performance for ‘‘cell 

identification’’ from 90 percent to 80 

percent. We are proposing 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 0 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 are proposing 

to change the criteria for acceptable 

performance for unexpected antibody 

detection from 80 percent accuracy to 

100 percent accuracy. We are proposing 

this change because it is critical for 

laboratories to identify any unexpected 

antibody when crossmatching blood in 

order to protect the public health and 

not impact patient care. 

III. Collection of Information 

Requirements 

Under the Paperwork Reduction Act 

of 1995 (PRA), we are required to 

publish a 60-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. 

To fairly evaluate whether an 

information collection should be 

approved by OMB, PRA section 

3506(c)(2)(A) of the PRA 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 burden 

estimates. 

• The quality, utility, and clarity of 

the information to be collected. 

• Our effort to minimize the 

information collection burden on the 

affected public, including the use of 

automated collection techniques. 

We are soliciting public comment on 

each of the section 3506(c)(2)(A)- 

required issues for the following 

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 are proposing 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 36,777 laboratories 

which is 368 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 a 

year which would take approximately 1 

hour. The total annual burden is 368 

hours (368 laboratories × 1 hour). A 

Clinical Laboratory Technologists/ 

Technicians would perform this task at 

an hourly wage of $25.59 as published 

in 2017 by the Bureau of Labor Statistics 

(https://www.bls.gov/oes/current/oes_

nat.htm). The wage rate would be 

$51.18 to include overhead and fringe 

benefits. The total cost would be 

$18,834 (368 hours × $51.18). 

B. Submission of PT Data by 

Laboratories 

At § 493.901(c)(6), we are proposing 

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. 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. In accordance with the 

implementing regulations of the PRA at 

5 CFR 1320.3(b)(2), we believe the 

ability for the PT programs to track this 

data already exists in their software; 

however, they may need to make minor 

modifications to their software in order 

to meet this requirement. If a PT 

program would need to update their 

software, we would estimate that the 

cost would be 15 hours for software 

modification. The total burden is 135 

hours (9 PT programs × 15 hours). 

However, this would not be an annual 

burden, rather it would only occur once 

when the requirement is implemented. 

A Software Developer, System Software 

would perform this task at an hourly 

wage of $107.48 as published in 2017 by 

the Bureau of Labor Statistics (https://

www.bls.gov/oes/current/oes_nat.htm). 

The wage rate would be $107.48 to 

include overhead and fringe benefits. 

The total high estimated cost would be 

$14,510 (135 hours × $107.48). For those 

PT programs who already have this 

mechanism in place, there would be no 

additional burden or cost to meet this 

requirement. 

C. Optional On-Site Visits to PT 

Programs 

At § 493.901(e), we propose to add the 

requirement that HHS may require onsite 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 


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normal course of business and is a usual 

and customary practice in accordance 

with implementing regulations at 42 

CFR 493, subpart I. 

D. PT Program Reapproval 

At § 493.901(f), we propose 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 would perform this task 

at an hourly wage of $17.96 as 

published in 2017 by the Bureau of 

Labor Statistics (https://www.bls.gov/ 

oes/current/oes_nat.htm). The wage rate 

would be $35.92 to include overhead 

and fringe benefits. The total cost would 

be $3,233 (90 hours × $35.92). 

E. Withdrawal of Approval of a PT 

Program 

At § 493.905, we propose 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 

are also proposing 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). 

IV. Response to Comments 

Because of the large number of public 

comments we normally receive on 

Federal Register documents, we are not 

able to acknowledge or respond to them 

individually. We will consider all 

comments we receive by the date and 

time specified in the DATES section of 

this preamble, and, when we proceed 

with a subsequent document, we will 

respond to the comments in the 

preamble to that document. 

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. 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. We based our decision 

to update the regulations and 

incorporate the changes proposed in 

this rule upon advice from the CLIAC. 

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)), and 

Executive Order 13771 on Reducing 

Regulation and Controlling Regulatory 

Costs (January 30, 2017). 

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 economicallysignificant regulatory actions that are 

likely to impose costs or benefits of 

$100 million or more in any given year. 

This proposed regulation is 

economically significant within the 

meaning of section 3(f)(1) of the 

Executive Order since the estimated cost 

alone is likely to exceed the $150 

million annual threshold. However, our 

upper limit of estimated impact is under 

the threshold of $150 million for the 

year of 2018 under Unfunded Mandates 

Reform Act (UMRA). The proposed rule, 

if finalized, would revise the CLIA PT 

requirements and would affect 

approximately 36,777 clinical 

laboratories now subject to participation 

in PT, resulting in some financial 

implications. In addition, this proposed 

rule, if finalized, would cause the seven 

existing CLIA-approved PT programs to 

incur some costs as they modify their 

programs to meet the requirements 

specified in this proposed rule. It may 

also have an effect on some state PT 

requirements. We prepared the RIA and 

found that it did not meet the UMRA 

threshold for a significant regulatory 

action. 

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 virtue of being 

nonprofit organizations or by meeting 

the Small Business Administration 

definition of a small business by having 

revenues of less than $7.5 million to 

$38.5 million in any one 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 2017 (https://www.aha.org/ 

system/files/2018-01/fast-facts-ushospitals-2017_0.pdf) and 100 percent 

of PT programs are nonprofit 

organizations. Individuals and states are 

not included in the definition of a small 

entity. We are voluntarily preparing a 

Regulatory Impact Analysis and are 

requesting public comments in this area 

to assist us in making this determination 

in the final rule. 


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25Bush, Laina. HHS Memo on Annual Update to 

the Unfunded Mandate Reform Act Threshold for 

2017, March 24, 2017. 

In addition, section 1102(b) of the 

Social Security Act (the 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 603 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 proposed 

rule, if finalized, would have a 

significant impact on small rural 

hospitals. Such hospitals often provide 

very limited laboratory services and 

may refer testing for the analytes we 

propose to add, to larger laboratories. 

For the small rural hospitals that have 

laboratories and perform testing for the 

analytes, we expect that our proposals 

will add minimal effort since they 

should already have PT policies and 

procedures in place. We are unable to 

estimate the number of laboratories that 

support small rural hospitals. We are 

requesting public comments in this area 

to assist us in making this determination 

in the final rule. 

Section 202 of the Unfunded 

Mandates Reform Act of 1995 (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 2018, that 

threshold is approximately $150 

million.25 We do not anticipate this 

proposed rule would impose an 

unfunded mandate on states, tribal 

governments, or the private sector of 

more than $150 million annually. We 

request comments from states, tribal 

governments, and the private sector on 

this assumption. 

Executive Order 13132 establishes 

certain requirements that an agency 

must meet when it promulgates a 

proposed rule (and subsequent final 

rule) that imposes substantial direct 

requirement costs on state and local 

governments, preempts state law, or 

otherwise has federalism implications. 

The proposed changes would 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. We do not believe 

that this rule would impose substantial 

direct compliance costs on state and 

local governments that are not required 

by statute. We do not believe that a 

significant number of laboratories 

affected by these proposals are operated 

by state or local governments. Therefore, 

the proposed modifications in these 

areas would not cause additional costs 

to state and local governments. 

We are proposing to require that each 

HHS-approved PT program have a 

minimum of ten laboratory participants 

before offering any PT analyte. 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). PT programs will 

determine if it is economically feasible 

to offer those analytes or if they should 

market their products to laboratories. 

Both of these activities are outside the 

scope of our authority. 

C. Anticipated Effects 

This proposed rule, if finalized, 

would impact approximately 36,777 

clinical laboratories (total of Certificate 

of Compliance and Certificate of 

Accreditation laboratories, as of January 

2017) required to participate in PT 

under the CLIA regulations 

implemented by the February 28, 1992 

final rule, seven current HHS-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 would result from the 

changes proposed in this rule, we are 

providing an analysis of the potential 

impact based on available information 

and certain assumptions. 

Implementation of these proposed 

requirements in a final rule would result 

in changes that are anticipated to have 

quantifiable impacts on laboratories 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) Proposed PT 

changes to the microbiology specialty; 

and (2) proposed PT changes to nonmicrobiology specialties. This was done 

because the PT requirements for 

microbiology differ from those 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. In the other specialties 

and subspecialties, PT participation is 

required and scores are given based on 

specific required analytes listed in the 

regulations. 

For both the microbiology PT changes 

and addition of proposed analytes to 

subpart I, we anticipate minimal burden 

to laboratories as CLIA already requires 

that laboratories must verify the 

accuracy of tests not currently listed in 

subpart I at least twice annually. We 

believe many laboratories meet this 

requirement by participating in 

proficiency testing voluntarily. 

However, we do not have a way of 

estimating how many of these 

participating laboratories actually meet 

the requirement through additional 

verification. Information on the costs of 

voluntary participation is also not 

reported. Although we cannot precisely 

predict how the proposed 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. 

As stated above, we are unable to 

estimate the number of laboratories 

voluntarily enrolled in PT which is not 

currently required in subpart I. Cost of 

adding a new analyte would range from 

$0.39 to $86.50; however, the majority 

of the costs/analyte are less than $5.00 

per analyte. 

1. Quantifiable Impacts for Laboratories 

CDC receives catalogs from all CLIAapproved PT programs annually. We 

estimated material costs for purchasing 

PT based on the range of 2017 catalog 

prices from the seven CLIA-approved 

PT programs. In estimating the costs for 

performing PT for all laboratory 

specialties that would be affected by 

this regulatory change, we assumed that 

the average national CMS 

reimbursement rate for Part B Medicare 

(CMS Virtual Research Data Center: 

https://www.resdac.org/cms-data/ 

request/cms-virtual-research-datacenter) was a reasonable estimate of the 

cost the laboratory incurs when testing 

each sample (or challenge) because 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 calculate that, on average, the 

impact would be between $721 and 


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$3,218 per laboratory, with laboratories 

having fewer analytes bearing a smaller 

burden. 

a. Impacts of Proposed PT Changes to 

the Microbiology Specialty 

Proposed changes to the microbiology 

specialty include changes in each of the 

subspecialties (bacteriology, 

mycobacteriology, mycology, 

parasitology, and virology) that would 

replace the types of services offered and 

the examples of organisms to be 

included over time with a proposed list 

of categories of tests and groups of 

microorganisms for which PT is 

required. In addition, changes are being 

proposed for each individual 

subspecialty that would require specific 

PT for certain microbiology tests and 

procedures. These changes, if finalized, 

could have a cost impact on 

laboratories. However, as stated in 

§ 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, Proficiency 

Testing Programs for Nonwaived 

Testing, a laboratory must verify the 

accuracy of that test or procedure at 

least twice annually. Although we can 

estimate how many microbiology 

laboratories voluntarily enroll in PT 

with HHS-approved PT programs to 

meet this requirement, we cannot 

estimate how many laboratories meet 

this requirement through other accuracy 

verification methods. The numbers of 

laboratories reported in Table 2 and 

Table 3 represent those laboratories the 

CDC was able to verify as voluntarily 

enrolled in PT for those types of 

microbiology tests not currently 

included in subpart I. The number of 

laboratories affected by this change as 

well as the cost can be estimated by 

adding the M1 (that is, laboratories 

already participating in required 

microbiology PT) and M2 (that is, 

laboratories not participating in a PT 

program for proposed microbiology PT) 

number in Table 2 and Table 3. For the 

7,160 affected microbiology laboratories, 

the estimated cost of the proposed 

quantifiable changes to required PT for 

each microbiology subspecialty follows. 

To estimate the costs that would be 

incurred by laboratories to purchase PT 

materials for the proposed changes to 

the microbiology specialty, if finalized, 

we compiled a range of PT material cost 

estimates per each challenge using 2017 

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. Independent 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 2017 catalog prices from the 

seven CLIA-approved PT programs. 

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. 

In estimating the number of 

microbiology laboratories that would be 

impacted by each of the proposed 

changes, we determined the numbers of 

Certificate of Compliance (CoC) and 

Certificate of Accreditation (CoA) 

laboratories for each microbiology 

subspecialty using the CMS Online 

Survey Certification & Reporting System 

(OSCAR)/Quality Improvement and 

Evaluation System (QIES) database. To 

categorize the laboratories as described 

below, the OSCAR/QIES database was 

used to determine the accreditation 

organization for each CoA laboratory. 

For the analysis of the impact on 

laboratories by the proposed 

microbiology PT changes, we used two 

laboratory categories: 

• Laboratories participating in a PT 

program for already required 

microbiology PT (Category M1). 

• Laboratories not participating in a 

PT program for proposed microbiology 

PT (Category M2). 

Category M1: Laboratories Already 

Participating in Required Microbiology 

PT 

For proposed 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 

Proposed Microbiology PT 

As stated, we used Certificate of 

Accreditation data to facilitate the 

estimation of the number of laboratories 

that would be subject to proposed 

microbiology PT and are not already 

participating in a PT program. Of the 

seven CLIA-approved accreditation 

organizations, data were provided by 

COLA showing how many of the 7,414 

COLA-accredited laboratories offer 

testing for four of the new microbiology 

tests we are proposing to add to the list 

for required PT. We used these data to 

estimate the percentage of COLAaccredited laboratories that provide 

testing for these microbiology tests. We 

assumed that COLA-accredited 

laboratories are similar to CoC 

laboratories and laboratories accredited 

by accreditation organizations other 

than the College of American 

Pathologists (CAP). Therefore, we 

assumed that the percentage of COLAaccredited laboratories that perform a 

specific microbiology test could be used 

to approximate the total number of 

laboratories that perform the test using 

the OSCAR/QIES data. For the proposed 

microbiology PT changes, 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 to all affected 

laboratories. 

(1) Effects of the Proposed PT Changes 

in the Bacteriology Subspecialty 

In the bacteriology subspecialty, the 

proposed changes 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 or 

resistance testing challenge per year. 


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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 would be impacted by 

this proposed change, if finalized, we 

calculated the number enrolled in Gram 

stain PT who do not report the bacterial 

morphology PT portion of the Gram 

stain module. Since this change would 

require that laboratories already 

performing PT report bacterial 

morphology in addition to Gram stain 

reaction on each challenge, we estimate 

the cost impact would be minimal. 

Since laboratories are already 

participating in Gram stain PT and we 

know the numbers of laboratories not 

currently participating in the 

determination of bacterial morphology, 

the range of estimated costs was 

determined 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 reimbursement rate for Part B 

Medicare; 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 

and 15 challenges for the high estimate 

(Tables 2 and 3). 

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 

for bacterial toxin detection are already 

meeting the proposed 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 

proposed 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 reimbursement rate for 

Part B Medicare; 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 

and 15 challenges for the high estimate 

(Tables 2 and 3). 

Currently, one sample or challenge 

per testing event is required for 

antimicrobial susceptibility testing in 

bacteriology. To evaluate the proposed 

impact of increasing the required 

antimicrobial susceptibility or 

resistance testing from currently 

required one challenge per year to a 

proposed 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 reimbursement rate for Part B 

Medicare; 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 

(Tables 2 and 3). Considering all of the 

potential cost impacts, the range of 

estimated impact for the proposed 

bacteriology subspecialty changes for 

the first year would be $101,785 to 

$2,599,552. 

(2) Effects of the Proposed PT Changes 

in the Mycobacteriology Subspecialty 

In the mycobacteriology subspecialty, 

the proposed changes that may have a 

cost impact include the addition of a 

second antimycobacterial susceptibility 

or resistance testing challenge per year. 

The same type of analysis that was 

performed to evaluate the proposed 

impact of increasing the required 

bacterial antimicrobial susceptibility or 

resistance testing from one challenge to 

two challenges per year was performed 

to evaluate the proposed impact of 

increasing the required 

antimycobacterial susceptibility or 

resistance testing from one challenge to 

two challenges per year (Tables 2 and 

3). The range of estimated impact for the 

proposed mycobacteriology subspecialty 

changes for the first year would be 

$12,558 to $39,420. 

(3) Effects of the Proposed PT Changes 

in the Mycology Subspecialty 

In the mycology subspecialty, the 

proposed changes that may have a cost 

impact include the addition of required 

PT for direct fungal antigen detection, 

detection of growth or no growth in 

culture media, and the addition of two 

antifungal susceptibility or resistance 

testing challenges per year. To evaluate 

the impact of the proposed regulated 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 proposed 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 proposed 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 reimbursement rate for 

Part B Medicare; 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 

and 15 challenges for the high estimate 

(Tables 2 and 3). 

The proposal to add detection of 

growth or no growth in culture media to 

the mycology PT identification would 

impact 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 of this 

proposal using the same methodology as 

was performed to determine the impact 

of the proposal to include direct fungal 

antigen detection (Tables 2 and 3). 

Because COLA did not indicate that 

any of their accredited laboratories 

participate in antifungal susceptibility 

or resistance testing, we assumed that 

no CoC or CoA laboratories other than 

those accredited by CAP would be 

required to participate in PT for 

antifungal susceptibility or resistance 

testing. Therefore, the cost impact of the 

proposed change to include two 

antifungal susceptibility or resistance 

testing challenges per year was 

calculated using the total number of 

category M1 laboratories that participate 

in CAP PT for antifungal susceptibility 

testing, the only program that offers 

challenges, as the number of impacted 

laboratories. The range of estimated 

costs was determined by using the 

number of CAP category M1 impacted 

laboratories that perform antifungal 

susceptibility or resistance testing; the 

estimate of the cost the laboratory incurs 

when testing each challenge; based on 

the average national CMS 

reimbursement rate for Part B Medicare; 

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 (Tables 2 

and 3). Considering all of the potential 

cost impacts, the range of estimated 

impact for the proposed mycology 


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subspecialty changes for the first year 

would be $41,235 to $422,406. 

(4) Effects of the Proposed PT Changes 

in the Parasitology Subspecialty 

In the parasitology subspecialty, the 

proposed change 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 

proposed PT requirements. Since CAPaccredited laboratories are already 

required to perform PT if they perform 

direct parasite antigen detection, we 

assumed they are already meeting the 

proposed 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 parasite antigen detection; the 

estimate of the cost the laboratory incurs 

when testing each challenge, using the 

average national CMS reimbursement 

rate for Part B Medicare; 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 and 15 

challenges for the high estimate (Tables 

2 and 3). Considering all of the potential 

cost impacts, the range of estimated 

impact for the proposed parasitology 

subspecialty changes for the first year 

would be $14,151 to $678,696. 

(5) Effects of the Proposed PT Changes 

in the Virology Subspecialty 

In the virology subspecialty, the 

proposed change that may have a cost 

impact includes the addition of two 

antiviral susceptibility or resistance 

testing challenges per year. Because 

COLA did not indicate that any of their 

accredited laboratories participate in 

antiviral susceptibility or resistance 

testing, we assumed that no CoC or CoA 

laboratories other than those accredited 

by CAP would be required to participate 

in PT for antiviral susceptibility or 

resistance testing. Therefore, the cost 

impact of the proposed change to 

include two antiviral susceptibility or 

resistance testing challenges per year 

was calculated using the total number of 

category M1 laboratories that participate 

in CAP PT for antiviral susceptibility or 

resistance testing, the only program that 

had subscribers to a PT module, as the 

number of impacted laboratories. The 

range of estimated costs was determined 

by using the number of CAP category 

M1 impacted laboratories that perform 

antiviral susceptibility or resistance 

testing; the estimate of the cost the 

laboratory incurs when testing each 

challenge, using the average national 

CMS reimbursement rate for Part B 

Medicare; 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 

(Tables 2 and 3). Considering all of the 

potential cost impacts, the range of 

estimated impact for the proposed 

virology subspecialty changes for the 

first year would be $216,318 to 

$314,145. 

TABLE 2—LOW ESTIMATE FOR PROPOSED MICROBIOLOGY PT REGULATORY CHANGES

Proposed PT regulation change 

Total number 

of affected M1 

laboratories 

Total number 

of affected M2 

laboratories 

Labor * 

Supply/ 

material 

cost ** 

Total low 

impact for 

one challenge 

Total low 

impact for 

microbiology 

regulation 

changes 

Gram Stain including Morphology ............................................. 26 0 $4.54 $4.67 $239.46 $386,047 

Bacterial Toxin Detection .......................................................... 0 1,542 14.22 11.44 39,567.72 

Antimicrobial susceptibility and/or resistance testing ............... 3,281 0 9.89 9.00 61,978.09 

Antimycobacterial susceptibility or resistance testing ............... 454 0 4.33 23.33 12,557.64 

Direct fungal antigen detection ................................................. 0 96 14.22 16.00 2,901.12 

Detection of growth or no growth in culture media— 

dermatophytes (DTM) ............................................................ 0 527 8.16 16.00 12,732.32 

Antifungal susceptibility or resistance testing ........................... 0 369 9.89 24.80 *** 12,800.61 

Direct parasite antigen detection .............................................. 0 533 14.22 12.33 14,151.15 

Antiviral susceptibility or resistance testing .............................. 332 0 230.11 95.67 3 108,158.96 

* Average national CMS reimbursement rate for Part B Medicare (CMS Virtual Research Data Center: https://www.resdac.org/cms-data/request/cms-virtual-research-data-center). 

** Low 2017 PT catalog price per challenge. 

*** Total low impact is multiplied by two for the proposal to add two new susceptibility or resistance testing challenges. 

TABLE 3—HIGH IMPACT FOR PROPOSED MICROBIOLOGY PT REGULATIONS

Proposed PT regulation change 

Total number 

of affected M1 

laboratories 

Total number 

of affected M2 

laboratories 

Labor 1 Supply/ 

material cost 2

Total high 

impact/for 

one challenge 

Total high 

impact/for 

15 challenges 

Total high 

impact for 

microbiology 

regulation 

changes 

Gram Stain including Morphology ................. 26 0 $4.54 $15.00 $508.04 $7,620.60 $4,054,219 

Bacterial Toxin Detection .............................. 0 1,542 14.22 91.50 163,020.24 2,445,303.60 

Antimicrobial susceptibility and/or resistance 

testing ........................................................ 3,281 0 9.89 34.80 146,627.89 N/A 

Antimycobacterial susceptibility or resistance 

testing ........................................................ 454 0 4.33 82.50 39,420.82 N/A 

Direct fungal antigen detection ..................... 0 96 14.22 31.80 4,417.92 66,268.80 

Detection of growth or no growth in culture 

media—dermatophytes (DTM) .................. 0 527 8.16 33.00 21,691.32 325,369.80 

Antifungal susceptibility or resistance testing 0 369 9.89 31.80 3 15,383.61 N/A 

Direct parasite antigen detection .................. 0 533 14.22 70.67 45,246.37 678,695.55 

Antiviral susceptibility or resistance testing .. 332 0 230.11 243.00 3 157,072.52 N/A 

1Average national CMS reimbursement rate for Part B Medicare (CMS Virtual Research Data Center: https://www.resdac.org/cms-data/request/cms-virtual-research-data-center). 2 High 2017 PT catalog price per challenge. 

3Total low impact is multiplied by two for the proposal to add two new susceptibility or resistance testing challenges. 


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b. Impacts of Proposed PT Changes to 

the Non-Microbiology Specialties/ 

Subspecialties 

The proposed changes in specialties 

and subspecialties other than 

microbiology include adding 29 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 

36,777 clinical laboratories that will be 

affected (19,287 Certificate of 

Compliance and 17,490 Certificate of 

Accreditation laboratories). This will be 

a new burden for some laboratories, but 

many laboratories are already paying for 

PT of these analytes. As previously 

mentioned, in §§ 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 

(Earley, Astles, and Breckenridge, 2017) 

that of those who were not already 

required by the CAP to perform PT on 

more than the CLIA-required analytes, 

39 percent purchased PT for 1 to 5 

analytes, 17 percent for 6 to 10 analytes, 

10 percent for 11 to 20 analytes, and 10 

percent for more than 20 analytes. We 

estimated the costs for proposed 

analytes by grouping all affected 

laboratories into four categories, 

calculating the number of laboratories in 

each category and calculated the costs 

using the analyte price and test 

reimbursement rate. We also propose to 

tighten acceptance limits of several 

currently-required analytes, which may 

have an impact on laboratories, but the 

cost impact is not included in our 

estimate. In addition, we are proposing 

to delete five currently-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 

proposed analytes: PT programs may 

offer analytes as an individual analyte 

or as part of a module that combines 

multiple analytes; some of the proposed 

analytes may already be offered but at 

a frequency other than the CLIArequired 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, either alone or in different 

combinations, we used a range of 

estimates based upon the 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 estimate 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 programs. For the 

higher cost estimate, we used the 

highest individual analyte price. In 

some cases, PT programs offer PT for the 

proposed analytes at different 

frequencies, that is, different numbers of 

events per year and different numbers of 

challenges per event. Therefore, to 

accurately estimate the future unit costs, 

we had to calculate the increased 

frequency for each analyte in order to 

achieve three events/year with five 

challenges per event. 

The proposed rule will have different 

impacts on CoA laboratories mainly 

because the CAP has strict requirements 

for PT participation that exceed CLIA 

minimal requirements, while other 

accreditation organizations may not. 

Therefore, our analysis starts with CAPaccredited laboratories as CAP is not 

only a large accreditation organization 

but also the largest PT program. In 

estimating the number of affected 

laboratories resulting from the proposed 

PT changes, if finalized, 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 for certain analytes and only 

for specific programs. Laboratories not 

accredited by the CAP may purchase PT 

materials from any CMS-approved PT 

program, including the CAP PT 

program. Therefore, we have designated 

four categories to estimate the cost 

impact, if the proposed changes are 

finalized: 

• Category 1: Laboratories accredited 

by the CAP that purchase material from 

the CAP PT program: The CAP provided 

us with the number of their accredited 

laboratories that are enrolled in their PT 

program for each proposed 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. 

• Category 2: CAP-accredited 

laboratories that purchase PT materials 

from other PT programs: For the 

analytes we considered adding, CAPaccredited laboratories are already 

required by CAP to enroll in a CAPapproved PT program. Ordinarily CAPaccredited laboratories enroll in the 

CAP PT program but they are permitted 

to enroll in PT from other CAPapproved 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 CAPaccredited laboratories in each of the 

non-CAP PT programs. The enrollment 

of laboratories not accredited by the 

CAP in each of the non-CAP PT 

programs (Category 4) was also 

available. Because the methodology to 

calculate Category 2 is the same as 

Category 4, we combine these two 

categories by using the enrollment of all 

laboratories (CAP-accredited 

laboratories and laboratories not 

accredited by the CAP) in each of the 

non-CAP PT program in the calculation. 

• Category 3: Laboratories not already 

enrolled in a PT program: To derive the 

minimum and maximum number of 

laboratories not already enrolled in a PT 

program that may provide testing for the 

proposed analytes, we began by 

estimating that there are 29,927 

laboratories that perform nonwaived 

testing and are not accredited by the 

CAP in the United States. To facilitate 

the calculations, we presumed that 

laboratories not accredited by the CAP 

will not purchase CAP PT. From the 

OSCAR/QIES database, we derived the 

number of laboratories not accredited by 

the CAP that provide testing in each 

specialty and reasoned that this was the 

maximum number of laboratories not 


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accredited by the CAP that might 

provide testing for each analyte. 

COLA provided us with the 

percentages of the approximately 7,414 

COLA-accredited laboratories that 

perform testing for each proposed 

analyte. We determined that COLAaccredited 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 proposed 

analyte could be used to estimate the 

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 proposed 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 non-CAP-accredited, 

CoC and CoA laboratories that may 

provide testing for each proposed 

analyte. 

For each proposed analyte, we 

calculated the number of CAPaccredited laboratories that buy from 

non-CAP PT programs by subtracting 

the CAP-accredited laboratories enrolled 

in CAP PT from the total number of 

CAP-accredited laboratories. 

We derived a low estimate of the total 

number of laboratories not accredited by 

the CAP and not enrolled in one of the 

non-CAP PT programs for each analyte. 

Negative estimates were taken as ‘‘0’’. 

This represents our low estimate of the 

number of laboratories that will need to 

purchase PT for each analyte. 

To obtain the high estimate for the 

number of laboratories not accredited by 

the CAP and not enrolled in one of the 

non-CAP PT programs, we took the high 

estimate of CoA laboratories not 

accredited by the CAP and CoC 

laboratories 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 OSCAR/ 

QIES to limit 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 the 

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 eight non-CAP PT 

programs and the maximum cost per 

sample that was the highest across all 

eight 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. 

• 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 and 

subtracted the number of CAPaccredited laboratories enrolled in a 

non-CAP PT program per analyte for 

this category. 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. 

c. Results 

We estimate that the overall impact of 

adding requirements for the proposed 

analytes in the specialties and 

subspecialties other than microbiology 

will range from $26 to $114 million for 

the first year (Table 4), if these proposed 

changed are finalized. Because of their 

larger number, and the fact that nonCAP accredited laboratories tend not to 

enroll in non-required PT as frequently 

as CAP-accredited laboratories do, we 

estimate that non-CAP accredited 

laboratories that are not enrolled in any 

PT program will have an impact 

between $16 and $100 million for the 

first year. We also estimate that 

laboratories that are enrolled in PT 

programs other than CAP will have a 

relatively minor impact, $5.4 million for 

the first year (Table 4). 

TABLE 4—ESTIMATED IMPACT FOR PROPOSED NON-MICROBIOLOGY PT REGULATIONS FOR THE FIRST YEAR IN 2017 

DOLLARS

Category Low estimate High estimate 

1. Laboratories accredited by CAP that purchase material from the CAP PT program .............. 4,516,673 .................... 4,516,673. 

2. Laboratories accredited by CAP that purchase PT materials from other PT programs .......... Included in Category 4 Included in Category 4. 

3. Laboratories not accredited by CAP that not already enrolled in other PT programs ............ 16,248,746 .................. 100,303,499. 

4. Laboratories not accredited by CAP enrolled in other PT programs (category 2 and 4 combined).5,351,565 .................... 4,103,686. 

Total increased cost .............................................................................................................. $26,116,984 ................ $114,275,423. 

For each of the four categories of 

affected laboratories previously 

described, Table 5 shows the total 

estimated range of annual cost for the 

proposed changes (including both 

microbiology and non-microbiology) in 

undiscounted 2017 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 2017 for the 

calculations displayed in Table 5 and 

we assume inflation-adjusted costs in 

future years to be the same as costs in 

the base year. 


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26Reilly AA Salkin IF McGinnis MR et al. 

Evaluation of mycology laboratory proficiency 

testing. J Clin Microbiol. 1999;37:2297–2305. 

27Parsons PJ Reilly AA Esernio-Jenssen D et al. 

Evaluation of blood lead proficiency testing: 

comparison of open and blind paradigms. Clin 

Chem. 2001;47:322–330. 

28Shahangian S and Snyder SR. Laboratory 

Medicine Quality Indicators: A Review of the 

Literature. American Journal of Clinical Pathology, 

2009; 131: 418–431. 

29 Jenny RW and Jackson KY. PT performance as 

a predictor of accuracy of routine patient testing for 

theophylline. Clin Chem 1993; 39:76–81. 

TABLE 5—TOTAL ESTIMATED ANNUAL COSTS FOR PROPOSED PT REGULATIONS

[All specialties in both microbiology and non-microbiology] 

Undiscounted (2017 $) Discounted at 3 percent Discounted at 7 percent 

Primary Low # High & Primary Low High Primary Low High 

2019 .................. $72,416,336 $26,503,031 $118,329,642 $68,259,342 $24,981,649 $111,537,036 $63,251,232 $23,148,774 $103,353,692 

2020 .................. 72,416,336 26,503,031 118,329,642 66,271,206 24,254,028 108,288,385 59,113,301 21,634,368 96,592,236 

2021 .................. 72,416,336 26,503,031 118,329,642 64,340,977 23,547,600 105,134,354 55,246,076 20,219,035 90,273,117 

2022 .................. 72,416,336 26,503,031 118,329,642 62,466,968 22,861,748 102,072,188 51,631,847 18,896,294 84,367,399 

2023 .................. 72,416,336 26,503,031 118,329,642 60,647,542 22,195,871 99,099,212 48,254,062 17,660,088 78,848,037 

# Total low cost is the sum of Table 2 (microbiology) and Table 4 (non-microbiology). 

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

2. Non-Quantifiable Impacts 

If the changes proposed in this rule 

are finalized, a number of nonquantifiable impacts will also result for 

PT programs and laboratories. We solicit 

comments and data to facilitate the 

determination of quantifiable estimates 

in the final rule. 

As with any currently required PT, if 

finalized, the proposed regulation 

would not require approved PT 

programs to offer additional analytes. 

Several programs already offer the 

analytes or tests that would be required 

by laboratories, and in these cases, we 

expect minimal impact on the PT 

programs. If the proposed changes 

outlined in this rule are finalized, 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. 

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 would mean 

offering an analyte or test for the first 

time, while for others it would mean 

increasing the yearly number of events 

and/or challenges per event. The costs 

would 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 

which would change the impact of the 

final rule. 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. 

If the proposed analyte deletions are 

finalized, some PT programs may cease 

offering the deleted analytes, 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. We solicit 

comments and data that would help us 

estimate the impact of the PT changes 

on PT programs in the final rule. 

Although we cannot precisely predict 

how the proposed changes may 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 we 

propose to delete, we cannot estimate 

the lowered expenditure for laboratories 

that stop buying PT materials and must 

begin doing something else to verify 

accuracy. Based upon 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 they currently spend 

on PT for the analytes we propose to 

delete, 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. 

3. Benefits 

While we cannot quantify the benefits 

that the proposed changes will bring, if 

finalized, we believe that the changes 

will facilitate more rapid identification 

of unacceptable practices in 

laboratories, especially for those 

laboratories that have not previously 

participated in PT. There are very few 

published reports that have investigated 

the impact of PT performance on testing 

accuracy or patient outcomes. In part 

this is because performing PT is now a 

standard practice for most analytes we 

are considering to add, so it is not 

possible to separate cohorts of PT users 

from non-users.26 27 28 29 In addition, 

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 benefiting 

physicians and healthcare providers 

that could occur with inaccurate testing. 

PT performance partially reflects 

daily clinical laboratory performance 

(Stull, Hearn, Hancock, Handsfield, and 

Collins, 1998). Updating acceptance 

limits 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 (Astles, 

Tholen, and Mitchell, 2016). Both 


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30Bainbridge, J., C.L. Wilkening, W. Rountree, R. 

Louzao, J. Wong, N. Perza, A. Garcia, T.N. Denny 

The Immunology Quality Assessment Proficiency 

Testing Program for CD3+4+ and CD3+8+ 

Lymphocyte Subsets: A ten year review via 

longitudinal mixed effects modeling. NIH Public 

Access Author Manuscript (July 2014). 

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.30

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 (Howerton, Krolak, 

Manasterski, and Handsfield, 2010). 

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 being proposed in this rule 

would incur any costs on the IVD 

industry, we expect the IVD industry to 

potentially benefit by the changes made 

in this proposed rule when finalized. 

Having the ability to track PT results for 

the added analytes will 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 (Howerton, Krolak, 

Manasterski, and Handsfield, 2010) that 

is expected to occur when this rule 

becomes finalized. 

D. Alternatives Considered 

In proposing these changes, several 

alternatives were considered. 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. 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 

compared to the proposed rule, 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. 

We are proposing to continue to require 

five challenges per event, with a passing 

score generally defined as a minimum of 

four challenges falling within the 

criteria for acceptable performance. A 

minimum of five challenges per event 

are necessary to follow the approach 

taken in the final regulation 

implementing CLIA ’88 which states 

that a minimum event score should be 

80 percent to be successful allowing for 

one missed result per event. 

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 impact of over $5.3 million to 

laboratories that would be required to 

perform susceptibility or resistance 

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 proposing to add 

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 we 

believed 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 acceptance limits as they were 

established in CLIA ’88, but we believe 

those are outdated given advancements 

in technology. We considered retaining 

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. We are 

requesting public comments related to 

alternative changes to be considered to 

assist us in finalizing this rule. 

E. Accounting Statement and Table 

We have prepared the following 

accounting statement showing the 

classification of expenditures associated 

with the provisions of this proposed 

rule. 

TABLE 6—ACCOUNTING TABLE

Category Primary 

estimate 

Minimum 

estimate 

Maximum 

estimate 

Units 

Source 

Year citation 

dollars 

Discount 

rate 

% 

Period 

covered 

Benefits 

Qualitative ....................................... • More effective detection of laboratories that provide inaccurate laboratory test 

results. 

• Increased confidence in laboratory test results. 

Preamble and Impact Analysis. 

Costs 

Annualized Monetized $/year .......... $72,416,336 $26,503,031 $118,329,642 2017 0 2019–2028 Impact Analysis. 

70,307,122 25,731,098 114,883,148 2017 3 2019–2028 

67,678,819 24,769,188 110,588,450 2017 7 2019–2028 


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F. Regulatory Reform Analysis Under 

E.O. 13771 

Executive Order 13771, titled 

Reducing Regulation and Controlling 

Regulatory Costs, was issued on January 

30, 2017 and requires that the costs 

associated with significant new 

regulations ‘‘shall, to the extent 

permitted by law, be offset by the 

elimination of existing costs associated 

with at least two prior regulations.’’ 

This proposed rule, if finalized, is 

considered an E.O. 13771 regulatory 

action. We estimate that this rule would 

generate $58.0 million in annualized 

costs in 2016 dollars, discounted at 7 

percent relative to year 2016 over a 

perpetual time horizon. Details on the 

estimated costs of this rule can be found 

in the preceding analyses. 

G. Conclusion 

We estimate that the cost to 

laboratories to participate in PT for the 

analytes and tests proposed in this rule 

would cost between $26,503,031 and 

$118,329,642 in 2017 dollars. Although 

the effect of the changes proposed will 

increase laboratory costs, 

implementation of these changes in a 

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 

would 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. 

In accordance with the provisions of 

Executive Order 12866, this proposed 

regulation was reviewed by the Office of 

Management and Budget. 

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 proposes to amend 

42 CFR part 493 as set forth below: 

PART 493—LABORATORY 

REQUIRMENTS 

■ 1. The authority citation for part 493 

is revised to read as follows: 

Authority: 42 U.S.C. 263a, 1302, 1395x(e), 

the sentence following 1395x(s)(11) through 

1395x(s)(16). 

■ 2. Section 493.2 is amended by— 

■ a. Adding the definitions of 

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

alphabetical order; 

■ b. Revising the definition of ‘‘Target 

value’’; and 

■ c. Adding the definition of 

‘‘Unacceptable score’’ in alphabetical 

order. 

The additions and revision read as 

follows: 

§ 493.2 Definitions. 

* * * * * 

Acceptance limit is the symmetrical 

tolerance (plus and minus) around the 

target value. 

* * * * * 

Peer group is 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 is: 

(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); or 

(ii) The mean established by a 

definitive method or reference methods; 

or 

(iii) The mean of a peer group, in 

instances when a definitive method or 

reference methods are not available; or 

(iv) If the peer group consists of fewer 

than 10 participants, ‘‘target value’’ 

means the overall mean after outlier 

removal (as defined in paragraph (1) of 

this definition) unless acceptable 

scientific reasons are available to 

indicate that such an evaluation is not 

appropriate. 

(2) [Reserved] 

* * * * * 

Unacceptable score is a PT result that 

is outside of the criteria for acceptable 

performance for a single challenge or 

sample. 

* * * * * 

■ 3. Section 493.20 is amended 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. Section 493.25 is amended 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. Section 493.801 is amended 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. Section 493.861 is amended 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. Section 493.901 is amended by— 

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

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

and (e), respectively; 

■ b. Adding new paragraph (a); 

■ c. Redesignating newly redesignated 

paragraphs (c)(6) and (7) as paragraphs 

(c)(7) and (8), respectively; 

■ d. Adding new paragraph (c)(6); 

■ e. Revising newly redesignated 

paragraph (c)(8); 

■ f. Adding paragraph (c)(9); 

■ g. Revising newly redesignated 

paragraph (e); and 

■ h. Adding paragraph (f). 

The additions and revisions read as 

follows: 

§ 493.901 Approval of proficiency testing 

programs. 

* * * * * 

(a) Require a minimum of ten 

laboratory participants before offering a 

proficiency testing analyte; 

* * * * * 


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(c) * * * 

(6) 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; 

* * * * * 

(8) A process to resolve technical, 

administrative, and scientific problems 

about program operations; and 

(9) A contractor performing 

administrative responsibilities as 

described in this section 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. 

* * * * * 

(e) HHS may require on-site visits for 

all initial proficiency testing program 

applications for CMS approval and 

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. Section 493.903 is amended— 

■ 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 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) 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 and the program must notify all 

laboratories enrolled of the nonapproval 

and the reasons for nonapproval within 

30 days of the 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 

PT program that is dissatisfied with a 

determination to disapprove the 

program, as applicable, may request that 

CMS reconsider the determination, in 

accordance with subpart D of part 488 

of this chapter. 

■ 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 growth or no growth 

in culture media; 

(B) Identification of bacteria; and 

(v) Antimicrobial susceptibility or 

resistance testing. 

(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 or resistance 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 or 

resistance 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 or 

resistance testing, the program must 

provide at least two samples per testing 

event that include one Gram-positive 

and one Gram-negative organism 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 

growth or no growth in culture media, 

identification of bacteria, and 

antimicrobial susceptibility or 

resistance 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 ten 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 it 

performs these procedures on patient 

specimens. 

(3) A laboratory’s performance will be 

evaluated on the basis of the average of 


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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. 

(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 growth or no growth in 

culture media is the presence or absence 

of bacteria or growth. 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 or 

resistance 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 or resistance 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 or resistance responses 

reported by the laboratory divided by 

the actual number of correct 

susceptibility or resistance responses 

determined by the program, multiplied 

by 100. For example, if a laboratory 

offers susceptibility or resistance 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; 

(ii) Detection and identification of 

mycobacteria which includes one of the 

following: 

(A) Detection of growth or no growth 

in culture media; or 

(B) Identification of mycobacteria; and 

(iii) Antimycobacterial susceptibility 

or resistance testing. 

(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 for antimycobacterial 

susceptibility or resistance for any 

designated isolate. 

(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 are acid-fast and 

challenges which do not contain acidfast organisms. 

(5) For antimycobacterial 

susceptibility or resistance testing, the 

program must provide at least two 

samples per testing event that have a 

predetermined pattern of susceptibility 

or resistance to the common 

antimycobacterial agents. 

(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 (7) 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 growth or no 

growth in culture media, identification 

of mycobacteria, and for 

antimycobacterial susceptibility or 

resistance testing. 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 ten 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 organism to the highest 

level that it performs these procedures 

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 

(6) of this section as determined in 

paragraph (b)(7) 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 growth or no growth in 

culture media is the presence or absence 

of bacteria or growth. The score is the 

number of correct responses divided by 


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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 

reportable, the sample grade would be 

1/(1 + 1) × 100 = 50 percent. 

(6) For antimycobacterial 

susceptibility or resistance 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 

antimycobacterial agents for which 

susceptibility or resistance testing is 

routinely performed patient specimens. 

A correct response for each 

antimycobacterial agent will be 

determined as described in paragraph 

(b)(1) of this section. Scoring for each 

sample is based on the number of 

correct susceptibility or resistance 

responses reported by the laboratory 

divided by the actual number of correct 

susceptibility or resistance responses as 

determined by the program, multiplied 

by 100. For example, if a laboratory 

offers susceptibility or resistance testing 

using three antimycobacterial agents 

and the laboratory reports correct 

responses for two of the three 

antimycobacterial agents, the 

laboratory’s grade would be 2/3 × 100 = 

67 percent. 

(7) The score for a testing event in 

mycobacteriology is the average of the 

scores determined under paragraphs 

(b)(4) through (6) 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; 

(ii) Detection and identification of 

fungi and aerobic actinomycetes which 

includes one of the following: 

(A) Detection of growth or no growth 

in culture media; or 

(B) Identification of fungi and aerobic 

actinomycetes; and 

(iii) Antifungal susceptibility or 

resistance testing. 

(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 for antifungal 

susceptibility or resistance for any 

designated isolate. 

(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) Dimorphic fungi; 

(D) Hyaline hyphomycetes; 

(E) Mucormycetes; and 

(iii) Aerobic actinomycetes. 

(4) For antifungal susceptibility or 

resistance testing, the program must 

provide at least two challenges per 

testing event that include fungi that 

have a predetermined pattern of 

susceptibility or resistance to the 

common antifungal agents. 

(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 (8) of 

this section. 

(1) The program determines the 

reportable fungi to be reported by direct 

fungal antigen detection, detection of 

growth or no growth in culture media, 

identification of fungi and aerobic 

actinomycetes, and antifungal 

susceptibility or resistance testing. 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 ten 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 it performs these procedures 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 

(6) of this section as determined in 

paragraph (b)(7) 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 growth or no growth in 

culture media is the presence or absence 

of fungi or growth. 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) For antifungal susceptibility or 

resistance 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 antifungal agents for which 


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susceptibility or resistance testing is 

routinely performed on patient 

specimens. A correct response for each 

antifungal agent will be determined as 

described in paragraph (b)(1) of this 

section. Scoring for each sample is 

based on the number of correct 

susceptibility or resistance responses 

reported by the laboratory divided by 

the actual number of correct 

susceptibility or resistance responses as 

determined by the program, multiplied 

by 100. For example, if a laboratory 

offers susceptibility or resistance testing 

using three antifungal agents and the 

laboratory reports correct responses for 

two of the three antifungal agents, the 

laboratory’s grade would be 2/3 × 100 = 

67 percent. 

(7) The score for a testing event is the 

average of the sample scores as 

determined under paragraphs (b)(4) 

through (6) 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 in 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 presence or absence 

of parasites; 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 which 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. 

(1) The program determines the 

reportable parasites to be detected by 

direct parasite antigen detection, 

detection of presence or absence of 

parasites, 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 ten 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 it 

performs these procedures 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 presence or absence of 

parasites is the presence or absence of 

parasites. 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 in 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; 

(ii) Detection and identification of 

viruses; and 

(iii) Antiviral susceptibility or 

resistance testing. 

(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. The program determines the 

reportable isolates and correct responses 

for antiviral susceptibility or resistance 

for any designated isolate. 

(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. 

(4) For antiviral susceptibility or 

resistance testing, the program must 


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provide at least two challenges per 

testing event that include viruses that 

have a predetermined pattern of 

susceptibility or resistance to the 

common antiviral agents. 

(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 (7) of 

this section. 

(1) The program determines the 

viruses to be reported by direct viral 

antigen detection, detection and 

identification of viruses, and antiviral 

susceptibility or resistance testing. 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 ten 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 it performs these procedures 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 

(6) of this section as determined in 

paragraph (b)(7) 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) For antiviral susceptibility or 

resistance 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 antiviral agents for which 

susceptibility or resistance testing is 

routinely performed patient specimens. 

A correct response for each antiviral 

agent will be determined as described in 

paragraph (b)(1) of this section. Scoring 

for each sample is based on the number 

of correct susceptibility or resistance 

responses reported by the laboratory 

divided by the actual number of correct 

susceptibility or resistance responses as 

determined by the program, multiplied 

by 100. For example, if a laboratory 

offers susceptibility or resistance testing 

using three antiviral agents and the 

laboratory reports correct responses for 

two of the three antiviral agents, the 

laboratory’s grade would be 2/3 × 100 = 

67 percent. 

(7) The score for a testing event is the 

average of the sample scores as 

determined under paragraphs (b)(4) and 

(6) of this section. 

■ 15. Section 493.923 is amended 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 in 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 ten 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. 

* * * * * 

■ 16. Section 493.927 is amended by 

revising paragraphs (a), (b), and (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: 

Alpha-l antitrypsin. 

Alpha-fetoprotein (tumor marker). 

Antinuclear antibody. 

Antistreptolysin O. 

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 ten 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)(i) 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. 

Criteria for Acceptable Performance 

The criteria for acceptable 

performance are— 


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Analyte or test Criteria for acceptable performance 

Alpha-1 antitrypsin .................................................................................... Target value ±20% or positive or negative. 

Alpha-fetoprotein (tumor marker) ............................................................. Target value ±20% or positive or negative. 

Antinuclear antibody ................................................................................. Target value ±3 SD or positive or negative. 

Antistreptolysin O ..................................................................................... Target value ±3 SD or positive or negative. 

Anti-Human Immunodeficiency virus (HIV) .............................................. Reactive (positive) or nonreactive (negative). 

Complement C3 ........................................................................................ Target value ±15% or positive or negative. 

Complement C4 ........................................................................................ Target value ±5 mg/dL or 20% (greater) or positive or negative. 

C-reactive protein (HS) ............................................................................. Target value ±1 mg/dL or 30% (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 ±15%. 

IgE ............................................................................................................ Target value ±20%. 

IgG ............................................................................................................ Target value ±20%. 

IgM ............................................................................................................ Target value ±20%. 

Infectious mononucleosis ......................................................................... Positive or negative. 

Rheumatoid factor .................................................................................... Target value ±3 SD or positive or negative. 

Rubella ...................................................................................................... Target value ±3 SD or positive or negative or immune or nonimmune. 

* * * * * 

■ 17. Section 493.931 is amended by 

revising paragraphs (a), (b), and (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. 

(b) Challenges per testing event. The 

minimum number of challenges per 

testing event a program must provide for 

each of the following analyte or test 

procedure is five serum, plasma or 

blood samples. 

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 

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, total 

Sodium 

Total iron binding capacity 

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 ten 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. 

Criteria for Acceptable Performance 

The criteria for acceptable 

performance are— 

Analyte or test Criteria for acceptable performance 

Alanine aminotransferase (ALT/SGPT) .................................................... Target value ±15%. 

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

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

Amylase .................................................................................................... Target value ±10%. 

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

Bilirubin, total ............................................................................................ Target value ±20%. 

Blood gas pCO2 ....................................................................................... Target value ±5 mm Hg or ±8% (greater). 

Blood gas pO2 .......................................................................................... Target value ±15 mmHg or 15% (greater). 

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%. 


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Analyte or test Criteria for acceptable performance 

Chloride .................................................................................................... Target value ±5%. 

Cholesterol, total ....................................................................................... Target value ±10%. 

Cholesterol, high density lipoprotein ........................................................ Target value ±20%. 

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

Creatine kinase (CK) ................................................................................ Target value ±20%. 

CK–MB isoenzymes ................................................................................. MB elevated (presence or absence) or Target value ±25% (greater). 

Creatinine ................................................................................................. Target value ±0.2 mg/dL or ±10% (greater). 

Ferritin ....................................................................................................... Target value ±20%. 

Gamma glutamyl transferase ................................................................... Target value ±5 U/L or ±15% (greater). 

Glucose (excluding measurements devices cleared by FDA for home 

use.).

Target value ±8% (greater). 

Hemoglobin A1c ....................................................................................... Target value ±10%. 

Iron, total ................................................................................................... Target value ±15%. 

Lactate dehydrogenase (LDH) ................................................................. Target value ±15%. 

Magnesium ............................................................................................... Target value ±15%. 

Phosphorus ............................................................................................... Target value ±0.3 mg/dL or ±10% (greater). 

Potassium ................................................................................................. Target value ±0.3 mmol/L. 

Prostate Specific Antigen, total ................................................................ Target value ±0.2 ng/dL or 20% (greater). 

Sodium ...................................................................................................... Target value ±4 mmol/L. 

Total Iron Binding Capacity (direct measurement) .................................. Target value ±20%. 

Total Protein ............................................................................................. Target value ±8%. 

Triglycerides ............................................................................................. Target value ±15%. 

Troponin I ................................................................................................. Target value ±0.9 ng/mL or 30% (greater). 

Troponin T ................................................................................................ Target value ±0.2 ng/mL or 30% (greater). 

Urea nitrogen ............................................................................................ Target value ±2 mg/dL or ±9% (greater). 

Uric acid .................................................................................................... Target value ±10%. 

* * * * * 

■ 18. Section 493.933 is amended by 

revising paragraphs (a), (b), and (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. 

Analyte or Test 

Cancer antigen (CA) 125 

Carcinoembryonic antigen (CEA) 

Cortisol 

Estradiol 

Folate, serum 

Follicle stimulating hormone 

Free thyroxine 

Human chorionic gonadotropin 

(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 ten 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 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. 

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%. 

Cortisol ...................................................................................................... Target value ±20%. 

Estradiol .................................................................................................... Target value ±30%. 

Folate, serum ............................................................................................ Target value ±1 ng/mL or ±30% (greater). 

Follicle stimulating hormone ..................................................................... Target value ±2 IU/L or ±18% (greater). 

Free thyroxine ........................................................................................... Target value ±0.3 ng/dL or ±15% (greater). 

Human chorionic ....................................................................................... Target value ±18% or positive or negative. 

Gonadotropin (excluding urine pregnancy tests done by visual color 

comparison categorized as waived tests).

Luteinizing hormone ................................................................................. Target value ±20%. 

Parathyroid hormone ................................................................................ Target value ±30%. 

Progesterone ............................................................................................ Target value ±25%. 


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Analyte or test Criteria for acceptable performance 

Prolactin .................................................................................................... Target value ±20%. 

Testosterone ............................................................................................. Target value ±20 ng/dL or ±30% (greater). 

T3 uptake .................................................................................................. Target value ±18%. 

Triiodothyronine ........................................................................................ Target value ±30%. 

Thyroid-stimulating hormone .................................................................... Target value ±20% or 0.2 mIU/L (greater). 

Thyroxine (greater) ................................................................................... Target value ±20% or 1.0 mcg/dL. 

Vitamin B12 .............................................................................................. Target value ±25%. 

* * * * * 

■ 19. Section 493.937 is amended by 

revising paragraphs (a), (b), and (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. 

Analyte or Test Procedure 

Acetaminophen, serum 

Alcohol (blood) 

Blood lead 

Carbamazepine 

Digoxin 

Gentamicin 

Lithium 

Phenobarbital 

Phenytoin 

Salicylate 

Theophylline 

Tobramycin 

Valproic Acid 

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 ten 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. 

Criteria for Acceptable Performance 

The criteria for acceptable 

performance are: 

Analyte or test Criteria for acceptable performance 

Acetaminophen ......................................................................................... Target value ±15%. 

Alcohol, blood ........................................................................................... Target Value ±20%. 

Blood lead ................................................................................................. Target Value ±10% or 2 mcg/dL (greater). 

Carbamazepine ........................................................................................ Target Value ±20%. 

Digoxin ...................................................................................................... Target Value ±15% or ±0.2 ng/mL (greater). 

Gentamicin ................................................................................................ Target Value ±25%. 

Lithium ...................................................................................................... Target Value ±15%. 

Phenobarbital ............................................................................................ Target Value ±15%. 

Phenytoin .................................................................................................. Target Value ±15% or ±2 mcg/dL (greater). 

Salicylate .................................................................................................. Target Value ±15%. 

Theophylline ............................................................................................. Target Value ±20%. 

Tobramycin ............................................................................................... Target Value ±20%. 

Valproic Acid ............................................................................................. Target Value ±20%. 

Vancomycin .............................................................................................. Target Value ±15% or ±2 mcg/dL (greater). 

* * * * * 

■ 20. Section 493.941 is amended by 

revising paragraphs (a), (b), and (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. 

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 ten 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 


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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. 

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 ±5%. 

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. 

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

* * * * * 

■ 21. Section 493.959 is amended by 

revising paragraphs (b) and (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 ten 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 ten 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— 

Analyte 

or test 

Criteria for 

acceptable 

performance 

ABO group ................. 100% accuracy. 

D (Rho) typing ........... 100% accuracy. 

Unexpected antibody 

detection.

100% accuracy. 

Analyte 

or test 

Criteria for 

acceptable 

performance 

Compatibility testing .. 100% accuracy. 

Antibody identification 80% + accuracy. 

* * * * * 

Dated: June 25, 2018. 

Seema Verma, 

Administrator, Centers for Medicare & 

Medicaid Services. 

Dated: December 17, 2018. 

Robert Redfield, MD 

Director, Centers for Disease Control and 

Prevention and Administrator, Agency for 

Toxic Substances and Disease Registry 

Dated: December 18, 2018. 

Alex M. Azar II, 

Secretary, Department of Health and Human 

Services. 

[FR Doc. 2018–28363 Filed 2–1–19; 8:45 am] 

BILLING CODE 4120–01–P 


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