[Federal Register Volume 68, Number 16 (Friday, January 24, 2003)]
[Rules and Regulations]
[Pages 3641-3714]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-1230]



[[Page 3639]]

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Part III





Department of Health and Human Services





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Centers for Medicare & Medicaid Services



Centers for Disease Control and Prevention



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42 CFR Part 493



Medicare, Medicaid, and CLIA Programs; Laboratory Requirements Relating 
to Qua

[[Page 3640]]

lity Systems and Certain Personnel Qualifications; Final Rule

  Federal Register / Vol. 68, No. 16 / Friday, January 24, 2003 / Rules 
and Regulations  
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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Medicare & Medicaid Services

Centers for Disease Control and Prevention

42 CFR Part 493

[CMS-2226-F]
RIN 0938-AK24


Medicare, Medicaid, and CLIA Programs; Laboratory Requirements 
Relating to Quality Systems and Certain Personnel Qualifications

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

ACTION: Final rule.

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SUMMARY: This final rule revises and responds to comments on certain 
laboratory requirements issued pursuant to the Clinical Laboratory 
Improvement Amendments of 1988 (CLIA), Pub. L. 100-578. Specifically, 
this final rule sets forth requirements for certain quality control 
(QC) provisions and personnel qualifications; consolidates and 
reorganizes the requirements for patient test management, QC, and 
quality assurance; and changes the consensus required for grading 
proficiency testing challenges.
    To ensure a smooth transition to the new provisions for directors 
of high complexity testing who are not board certified (but who have 
doctoral degrees), we will not be holding facilities out of compliance 
with the provisions of the rule concerning directors who are not board 
certified until the effective date of this new rule, to the extent the 
facilities are otherwise in compliance with the requirements for 
laboratory directors.

EFFECTIVE DATES: This final rule is effective on April 24, 2003, except 
Sec.  493.1443(b)(3) is effective on February 24, 2003.
    Compliance Dates: To ensure a clear transition from the board 
certification provisions of the former rule at 42 CFR 493.1443(b)(2) 
that have a compliance date of December 31, 2002 (as set forth in 65 FR 
82941), we will not be holding facilities out of compliance with the 
former rule until the effective date of the parallel provisions of this 
new rule to the extent that facilities are otherwise in compliance with 
the regulations for laboratory directors.

FOR FURTHER INFORMATION CONTACT: Rhonda S. Whalen (CDC), (770) 488-
8155, Judith A. Yost (CMS), (410) 786-3531.

SUPPLEMENTARY INFORMATION: 
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I. Background

    On February 28, 1992, we published a final rule with comment period 
in the Federal Register (57 FR 7002) that set forth the requirements 
for laboratories that are subject to the Clinical Laboratory 
Improvement Amendments of 1988 (CLIA).
    Under the provisions of the sentence following section 1861(s)(15) 
through 1861(s)(17) of the Social Security Act, (the Act) any 
laboratory that wants to be paid for services furnished to Medicare 
beneficiaries must meet the requirements of section 353 of the Public 
Health Services Act. Subject to specified exceptions, all laboratories, 
regardless of whether they receive payment from the Medicare or 
Medicaid programs must have a current and valid CLIA certificate to 
test human specimens. The February 28, 1992 final rule with comment 
period established uniform requirements based on the complexity of 
testing performed by laboratories regardless of the laboratory's 
location, size, or type. In the interest of public health, we included 
requirements in the February 28, 1992 final rule with comment period to 
ensure the quality of laboratory services.
    We recognized that it would take time and resources for 
laboratories to understand and to implement the new requirements 
contained in the February 28, 1992 final rule with comment period. This 
final rule completes the phase-in of certain requirements where the 
comments supported taking this action.
    The phased-in provision included quality control (QC) requirements 
applicable to moderate complexity tests and the date by which an 
individual with a doctorial degree must possess board certification to 
qualify as a director of a laboratory that performs high complexity 
testing.
    During the phase-in, the Food and Drug Administration (FDA) was to 
establish a process to review and clear manufacturers' QC instructions 
for CLIA QC purposes. Because the CLIA program is user fee funded, we 
decided it would be prudent to wait until the phase-in period ended 
before implementing the FDA QC review. This afforded us the survey 
experience necessary to determine whether an additional FDA review 
process beyond that already in place as part of the premarket review 
would be of benefit to laboratories. We realized through our experience 
inspecting laboratories that an additional FDA review would not be of 
such benefit. We decided to remove this prospective provision. 
Therefore, we are removing all references to the FDA CLIA QC clearance 
process that was not implemented.
    The phase-in effective dates contained in the February 28, 1992 
final rule with comment period were further extended in the final rules 
with comment period published on December 6, 1994 in the Federal 
Register (59 FR 62606), May 12, 1997 in the Federal Register (62 FR 
25855), October 14, 1998 in the Federal Register (63 FR 55031), and 
December 29, 2000 in the Federal Register (65 FR 82941).
    The extensions allowed previously unregulated laboratories time to 
understand and implement these requirements. The extensions also 
provided the Department of Health and Human Services (HHS) additional 
time to issue revised QC requirements, review board certification 
program requests for approval, and ensure that laboratory directors 
with a doctoral degree had sufficient time to successfully complete the 
requirements for board certification.
    On December 28, 2001, we published a proposed rule in the Federal 
Register (66 FR 67163) seeking comments on provisions to revise and 
expand the qualification requirements by which an individual with a 
doctoral degree in a chemical, physical, biological, or clinical 
laboratory science from an accredited institution may qualify to serve 
as a director of a laboratory performing high complexity testing. The

[[Page 3641]]

three proposed alternative qualification pathways were as follows:
    [sbull] On or after January 1, 2003, be certified and continue to 
be certified by a board approved by HHS.
    [sbull] Before January 1, 2003, must have served or be serving as a 
director of a laboratory performing high complexity testing and must 
have at least 2 years of laboratory training or experience, or both; 
and 2 years experience directing or supervising high complexity 
testing.
    [sbull] Have at least 6 years of laboratory training or experience, 
or both, including 2 years of experience directing or supervising high 
complexity testing.
    In this final rule, effective April 24, 2003, all laboratories must 
meet and follow the QC requirements. In addition, we are setting forth 
qualification requirements for an individual with a doctoral degree to 
serve as a director of a laboratory performing high complexity testing. 
Effective February 24, 2003, an individual with a doctoral degree may 
qualify to serve as a director of a laboratory that performs high 
complexity testing if he or she is certified and continues to be 
certified by a board approved by HHS; or before the effective date of 
this rule, has served or is serving as a director of a laboratory 
performing high complexity testing and has acquired at least 2 years of 
laboratory training or experience, or both, and 2 years of experience 
directing or supervising high complexity testing.
    The qualification requirements for high complexity laboratory 
directors that are contained in this final rule will become effective 
February 24, 2003. To ensure a smooth transition to these new 
provisions, we will not be holding facilities out of compliance with 
the Board certified regulations of the former rule until the effective 
date of this new rule, to the extent the facilities are otherwise in 
compliance with the regulations for laboratory directors.
    In addition, we are addressing the comments received in response to 
the February 28, 1992 final rule with comment period concerning part 
493 of title 42 of the Code of Federal Regulations (CFR), subparts I, 
J, K, M, and P; comments received in response to the date-extension 
rules for certain provisions of subparts K and M; and comments to the 
December 28, 2001 proposed rule regarding qualification requirements 
for directors of laboratories performing high complexity testing.

II. Highlights and Organization of Final Rule

    This regulation contains revisions to part 493 of title 42 of the 
CFR. We have renamed, reorganized, and consolidated similar 
requirements into one section, deleted duplicate requirements, and 
reworded numerous requirements to maintain and/or clarify their 
original intent, making the revised regulation easier to read and 
understand. In addition to specific changes to subparts I, J, K, M, and 
P, applicable technical and conforming changes were also made to other 
subparts.
    The organization of this regulation now reflects the flow of a 
patient specimen through the laboratory, that is, from receipt of the 
specimen with the test request through test performance and test result 
reporting. In addition, this final rule more accurately describes the 
testing requirements and laboratory assessment activities.
    In this final rule, the former Subpart I--Proficiency Testing 
Programs for Tests of Moderate Complexity (Including the Subcategory), 
High Complexity, or Any Combination of These Tests has been renamed 
Proficiency Testing Programs for Nonwaived Testing. In addition, in 
each specialty and subspecialty area of the subpart, we are restoring 
the requirement for the 80 percent agreement used by proficiency 
testing programs prior to the February 28, 1992 final rule with comment 
period.
    The requirements formerly in Subpart J--Patient Test Management for 
Moderate Complexity (Including the Subcategory), High Complexity, or 
Any Combination of These Tests; Subpart K--Quality Control for Tests of 
Moderate Complexity (Including the Subcategory), High Complexity, or 
Any Combination of These Tests; and Subpart P--Quality Assurance for 
Moderate Complexity (Including the Subcategory) or High Complexity 
Testing, or Any Combination of These Tests, are consolidated and 
reorganized into a new Subpart J--Facility Administration for Nonwaived 
Testing, and Subpart K--Quality Systems for Nonwaived Testing.
    As revised by this issuance, subpart J consolidates and clarifies 
the facility administration requirements for laboratories performing 
nonwaived testing. These include requirements for facility space, 
utilities and safety, transfusion services, and record and specimen 
retention. Also, subpart J now specifies that laboratories must comply 
with Federal, State, and local laboratory requirements. This will allow 
CMS to support a Federal, State, or local government that seeks to 
protect the public from actions it finds would be detrimental to public 
health. In addition, the requirements formerly at Sec.  493.1111 (now 
at Sec.  493.1242(c)) have been revised to allow CLIA-certified 
laboratories to refer specimens to laboratories operated under the 
Veterans Administration (VA), the Department of Defense (DOD), and 
CLIA-exempt laboratories within a State whose licensure program has 
been granted approval under subpart E.
    Requirements pertaining to the total testing process (preanalytic, 
analytic, and postanalytic) are now in subpart K. Specifically, subpart 
K has been revised to eliminate the QC requirements formerly at Sec.  
493.1202 and provisions pertaining to the FDA review and approval of 
manufacturers' test system QC for CLIA purposes as specified at Sec.  
493.1203 in the February 28, 1992 final rule with comment period. Also, 
subpart K is now structured to correlate with the movement of a 
specimen through the laboratory from acquisition to examination or 
testing, and reporting of results. The requirements were not 
substantively changed to correspond to the testing process, but we did 
eliminate redundant requirements and revise others for clarification.
    In addition, subpart K now incorporates the requirements formerly 
in Subpart P--Quality Assurance; Moderate Complexity (Including the 
Subcategory) or High Complexity Testing, or Any Combination of These 
Tests. These requirements are now located under the appropriate 
sections in subpart K, that is, General Laboratory Systems, Preanalytic 
Systems, Analytic Systems, and Postanalytic Systems. We listed the 
quality assurance (renamed quality assessment (QA) to more clearly 
reflect the activities performed) activities for each phase of testing. 
For example, QA requirements for preanalytic activities, such as 
monitoring the medical necessity and completeness of test request 
information solicited and obtained by the laboratory, now appear at the 
end of the preanalytic section of subpart K under Sec.  493.1249. We 
believe that integrating the QA requirements into the various phases of 
the testing process enhances the understanding of the vital and 
important role QA plays in ensuring that quality services are provided 
by the laboratory throughout the entire testing process. To further 
emphasize and clarify the essential components of a comprehensive QA 
program, we are reiterating in each assessment section the laboratory's 
responsibility to: (1) Establish and follow written polices and 
procedures for an ongoing mechanism to monitor and assess each of its 
activities; (2) take corrective actions, as necessary, based on these 
assessments; (3) review the effectiveness of the assessments and 
corrective actions

[[Page 3642]]

taken; (4) revise policies and procedures, as necessary, to prevent 
recurrences of problems; (5) discuss the assessment activities and 
findings with the appropriate staff; and (6) document all assessment 
activities. To ensure the clarity of this final rule, many of the QA 
requirements from the former subpart P had to be rewritten.
    To conform with the names of the new subparts I, J, and K, the 
former Subpart M--Personnel for Moderate Complexity (Including the 
Subcategory) and High Complexity Testing has been renamed Personnel for 
Nonwaived Testing. In subpart M, we are finalizing the qualification 
requirements for directors of laboratories performing high complexity 
testing at Sec.  493.1443(b)(3). In addition, we are revising Sec.  
493.1443(b)(3)(i) by removing the reference to specific boards approved 
by HHS. All HHS-approved boards are listed on the Internet at http://cms.hhs.gov/clia/dirc/con.asp. HHS-approved boards will also be listed 
in Appendix C of the State Operations Manual (CMS Pub. 7), subpart M. 
This change will allow greater flexibility to update the list of HHS-
approved boards. Also, we are announcing two new HHS-approved boards; 
the National Registry for Clinical Chemistry at the doctoral level and 
the American Board of Forensic Toxicology.
    To clarify these changes, we have provided a distribution table, 
which contains a detailed list of sections that have been removed or 
redesignated.

III. Distribution Table

    The following crosswalk table enables the reader to easily locate 
where the requirements from the former rule have been relocated. It 
lists the former section titles along with the section titles as they 
appear in this final rule. In addition, the reorganized regulation now 
follows the path of patient specimens as they proceed through the 
clinical laboratory. This organizational structure was adopted at the 
recommendation of the Clinical Laboratory Improvement Advisory 
Committee to assist laboratories in better understanding the basic CLIA 
requirements.

                            Table.--Crosswalk
------------------------------------------------------------------------
                              Requirements in this
   Former requirements and      final rule (part      Sections in this
 former sections (part 493,    493, subparts J, K,       final rule
  subparts J, K, M, and P)           and M)
------------------------------------------------------------------------
Patient test management;
 moderate complexity
 (including the
 subcategory), or high
 complexity testing, or any
 combination of these tests:
    Sec.   493.1101--         Specimen              Sec.  Sec.
     Introductory text.        identification and    493.1232;
                               integrity.
                              Preanalytic systems.  493.1240;
                              Postanalytic systems  493.1290
Procedures for specimen
 submission and handling:
    Sec.   493.1103(a)......  Specimen              Sec.  Sec.
                               identification and    493.1232;
                               integrity.
                              Specimen submission,  493.1242(a)(1)
                               handling, and         through (a)(6);
                               referral.
                              Procedure manual....  493.1251(b)(1)
    Sec.   493.1103(b)......  Specimen submission,  Sec.  Sec.
                               handling, and         493.1242(a)(8) and
                               referral.             (d);
                              Procedure manual....  493.1251(b)(1)
    Sec.   493.1103(c)......  Removed
Test requisition:
    Sec.   493.1105--         Retention             Sec.  Sec.
     Introductory text.        requirements.         493.1105(a)(1);
                              Test request........  493.1241(a), (b),
                                                     (c), and (d)
    Sec.   493.1105(a)......  Test request........  Sec.
                                                     493.1241(c)(2)
    Sec.   493.1105(b)......  Test request........  Sec.
                                                     493.1241(c)(1)
    Sec.   493.1105(c)......  Test request........  Sec.
                                                     493.1241(c)(4)
    Sec.   493.1105(d)......  Test request........  Sec.
                                                     493.1241(c)(6)
    Sec.   493.1105(e)......  Test request........  Sec.
                                                     493.1241(c)(3) and
                                                     (c)(7)
    Sec.   493.1105(f)......  Test request........  Sec.  Sec.
                                                     493.1241(c)(3),
                                                     (c)(5), and (c)(8)
                              Specimen submission,  493.1242(a)(3)
                               handling, and
                               referral.
Test records:
    Sec.   493.1107--         Retention             Sec.  Sec.
     Introductory text.        requirements.         493.1105(a)(3);
                              Specimen              493.1232;
                               identification and
                               integrity.
                              Test records........  493.1283(a)(4) and
                                                     (b)
    Sec.   493.1107(a)......  Test records........  Sec.
                                                     493.1283(a)(1)
    Sec.   493.1107(b)......  Specimen submission,  Sec.  Sec.
                               handling, and         493.1242(b);
                               referral.
                              Test records........  493.1283(a)(2)
    Sec.   493.1107(c)......  Test records........  Sec.
                                                     493.1283(a)(3)
    Sec.   493.1107(d)......  Test records........  Sec.
                                                     493.1283(a)(4)
Test report:
    Sec.   493.1109--         Retention             Sec.  Sec.
     Introductory text.        requirements.         493.1105(a)(3)(ii),
                                                     (a)(6)(i),
                                                     (a)(6)(ii) and (b);
                              Postanalytic systems  493.1290;
                              Test report.........  493.1291(b), (c)(3),
                                                     and (f)
    Sec.   493.1109(a)......  Confidentiality of    Sec.  Sec.
                               patient information.  493.1231;
                              Postanalytic systems  493.1290;
                              Test report.........  493.1291(a) and
                                                     (c)(3)
    Sec.   493.1109(b)......  Test report.........  Sec.  Sec.
                                                     493.1291(c)(2),
                                                     (c)(4), and (c)(6)
    Sec.   493.1109(c)......  Test report.........  Sec.
                                                     493.1291(c)(7)
    Sec.   493.1109(d)......  Test report.........  Sec.   493.1291(d)
    Sec.   493.1109(e)......  Test report.........  Sec.   493.1291(f)
    Sec.   493.1109(f)......  Procedure manual....  Sec.  Sec.
                                                     493.1251(b)(13);
                              Test report.........  493.1291(g)

[[Page 3643]]

 
    Sec.   493.1109(g)......  Test report.........  Sec.   493.1291(e)
    Sec.   493.1109(h)......  Test report.........  Sec.   493.1291(j)
Referral of specimens:
    Sec.   493.1111--         Specimen submission,  Sec.   493.1242(c)
     Introductory text.        handling, and
                               referral.
    Sec.   493.1111(a)......  Test report.........  Sec.
                                                     493.1291(i)(1)
    Sec.   493.1111(b)......  Test report.........  Sec.
                                                     493.1291(i)(2)
    Sec.   493.1111(c)......  Test report.........  Sec.
                                                     493.1291(i)(3)
General quality control;
 moderate complexity
 (including the subcategory)
 or high complexity testing,
 or any combination of these
 tests:
    Sec.   493.1201(a)......  Removed
    Sec.   493.1201(a)(1)...  Removed
    Sec.   493.1201(a)(2)...  Facility              Sec.  Sec.
                               Administration.       493.1100
                              General laboratory    493.1230
                               systems.
                              Preanalytic systems.  493.1240
                              Analytic systems....  493.1250
                              Control Procedures..  493.1256(d)
                              Postanalytic systems  493.1290
    Sec.   493.1201(b)......  Analytic systems....  Sec.  Sec.
                                                     493.1250;
                              Procedure manual....  493.1251(b)(7)
Moderate or high complexity
 testing, or both, Effective
 from September 1, 1992 to
 December 13, 2000:
    Sec.   493.1202(a)......  Facility              Sec.  Sec.
                               administration.       493.1100;
                              Subpart K--Quality    493.1201 through
                               systems for           493.1227
                               nonwaived testing.
    Sec.   493.1202(b)......  Facility              Sec.  Sec.
                               administration.       493.1100;
                              Subpart K--Quality    493.1201 through
                               systems for           493.1227
                               nonwaived testing.
    Sec.   493.1202(c)......  Facility              Sec.  Sec.
                               administration.       493.1100;
                              Subpart K--Quality    493.1201 through
                               systems for           493.1227
                               nonwaived testing.
    Sec.   493.1202(c)(1)...  Test systems,         Sec.  Sec.
                               equipment,            493.1252(a);
                               instruments,
                               reagents,
                               materials, and
                               supplies.
                              Maintenance and       493.1254(a)(1) and
                               function checks.      (a)(2)
                              Control procedures..  493.1256(d)(2)
    Sec.   493.1202(c)(2)...  Procedure manual....  Sec.   493.1251
    Sec.   493.1202(c)(3)...  Calibration and       Sec.   493.1255
                               calibration
                               verification
                               procedures.
    Sec.   493.1202(c)(4)...  Control procedures..  Sec.   493.1256
    Sec.   493.1202(c)(5)...  Control procedures..  Sec.
                                                     493.1256(d)(1)
    Sec.   493.1202(c)(6)...  Corrective actions..  Sec.   493.1282
    Sec.   493.1202(c)(7)...  Retention             Sec.
                               requirements.         493.1105(a)(3)
Moderate or high complexity
 testing, or both effective
 beginning 12/31/00:
    Sec.   493.1203--         Removed
     Introductory text.
    Sec.   493.1203(a)......  Removed
    Sec.   493.1203(b)......  Removed
Facilities:
    Sec.   493.1204--         Facilities..........  Sec.   493.1101(a)
     Introductory text.
    Sec.   493.1204(a)......  Facilities..........  Sec.  Sec.
                                                     493.1101(a)(1) and
                                                     (a)(2)
    Sec.   493.1204(b)......  Facilities..........  Sec.   493.1101(d)
Test methods, equipment,
 instrumentation, reagents,
 materials, and supplies:
    Sec.   493.1205--         Facility Test         Sec.  Sec.
     Introductory text.        systems, equipment,   493.1101(b);
                               instruments,          493.1252
                               reagents,
                               materials, and
                               supplies.
    Sec.   493.1205(a)......  Test systems,         Sec.   493.1252(a)
                               equipment,
                               instruments,
                               reagents,
                               materials, and
                               supplies.
    Sec.   493.1205(b)......  Facilities..........  Sec.   493.1101(b)
    Sec.   493.1205(c)......  Test systems,         Sec.   493.1252(b)
                               equipment,
                               instruments,
                               reagents,
                               materials, and
                               supplies.
    Sec.   493.1205(c)(1)...  Test systems,         Sec.   493.1252(b)
                               equipment,
                               instruments,
                               reagents,
                               materials, and
                               supplies.
    Sec.   493.1205(c)(1)(i)  Test systems,         Sec.
                               equipment,            493.1252(b)(1)
                               instruments,
                               reagents,
                               materials, and
                               supplies.
    Sec.                      Test systems,         Sec.
     493.1205(c)(1)(ii).       equipment,            493.1252(b)(2)
                               instruments,
                               reagents,
                               materials, and
                               supplies.
    Sec.                      Test systems,         Sec.
     493.1205(c)(1)(iii).      equipment,            493.1252(b)(3)
                               instruments,
                               reagents,
                               materials, and
                               supplies.

[[Page 3644]]

 
    Sec.                      Test systems,         Sec.
     493.1205(c)(1)(iv).       equipment,            493.1252(b)(4)
                               instruments,
                               reagents,
                               materials, and
                               supplies.
    Sec.   493.1205(c)(2)...  Corrective actions..  Sec.
                                                     493.1282(b)(3)
    Sec.   493.1205(d)......  Test systems,         Sec.   493.1252(c)
                               equipment,
                               instruments,
                               reagents,
                               materials, and
                               supplies.
    Sec.   493.1205(d)(1)...  Test systems,         Sec.
                               equipment,            493.1252(c)(1)
                               instruments,
                               reagents,
                               materials, and
                               supplies.
    Sec.   493.1205(d)(2)...  Test systems,         Sec.
                               equipment,            493.1252(c)(2)
                               instruments,
                               reagents,
                               materials, and
                               supplies.
    Sec.   493.1205(d)(3)...  Test systems,         Sec.
                               equipment,            493.1252(c)(3)
                               instruments,
                               reagents,
                               materials, and
                               supplies.
    Sec.   493.1205(d)(4)...  Test systems,         Sec.
                               equipment,            493.1252(c)(4)
                               instruments,
                               reagents,
                               materials, and
                               supplies.
    Sec.   493.1205(e)......  Test systems,         Sec.   493.1252(d)
                               equipment,
                               instruments,
                               reagents,
                               materials, and
                               supplies.
    Sec.   493.1205(e)(1)...  Test systems,         Sec.  Sec.
                               equipment,            493.1252(d);
                               instruments,
                               reagents,
                               materials, and
                               supplies.
                              Immunohematology....  493.1271(b)
    Sec.   493.1205(e)(2)...  Test systems,         Sec.   493.1252(e)
                               equipment,
                               instruments,
                               reagents,
                               materials, and
                               supplies.
Procedure manual:
    Sec.   493.1211(a)......  Procedure manual....  Sec.   493.1251(a)
    Sec.   493.1211(b)......  Procedure manual....  Sec.   493.1251(b)
    Sec.   493.1211(b)(1)...  Procedure manual....  Sec.
                                                     493.1251(b)(1)
    Sec.   493.1211(b)(2)...  Procedure manual....  Sec.
                                                     493.1251(b)(2)
    Sec.   493.1211(b)(3)...  Procedure manual....  Sec.  Sec.
                                                     493.1251(b)(3);
                              Histocompatibility..  493.1278(d)(7)
    Sec.   493.1211(b)(4)...  Procedure manual....  Sec.
                                                     493.1251(b)(4)
    Sec.   493.1211(b)(5)...  Procedure manual....  Sec.
                                                     493.1251(b)(5)
    Sec.   493.1211(b)(6)...  Procedure manual....  Sec.
                                                     493.1251(b)(6)
    Sec.   493.1211(b)(7)...  Procedure manual....  Sec.
                                                     493.1251(b)(7)
    Sec.   493.1211(b)(8)...  Procedure manual....  Sec.
                                                     493.1251(b)(8)
    Sec.   493.1211(b)(9)...  Procedure manual....  Sec.
                                                     493.1251(b)(9)
    Sec.   493.1211(b)(10)..  Procedure manual....  Sec.
                                                     493.1251(b)(10)
    Sec.   493.1211(b)(11)..  Procedure manual....  Sec.
                                                     493.1251(b)(11)
    Sec.   493.1211(b)(12)..  Procedure manual....  Sec.
                                                     493.1251(b)(12)
    Sec.   493.1211(b)(13)..  Specimen submission,  Sec.  Sec.
                               handling, and         493.1242(a)(4);
                               referral.
                              Procedure manual....  493.1251(b)(1)
    Sec.   493.1211(b)(14)..  Procedure manual....  Sec.
                                                     493.1251(b)(13)
    Sec.   493.1211(b)(15)..  Procedure manual....  Sec.
                                                     493.1251(b)(14)
    Sec.   493.1211(b)(16)..  Procedure manual....  Sec.
                                                     493.1251(b)(1)
    Sec.   493.1211(c)......  Procedure manual....  Sec.   493.1251(c)
    Sec.   493.1211(d)......  Procedure manual....  Sec.   493.1251(d)
    Sec.   493.1211(e)......  Procedure manual....  Sec.   493.1251(d)
    Sec.   493.1211(f)......  Procedure manual....  Sec.   493.1251(d)
    Sec.   493.1211(g)......  Retention             Sec.  Sec.
                               requirements.         493.1105(a)(2);
                              Procedure manual....  493.1251(e)
Establishment and
 verification of method
 performance specifications:
    Sec.   493.1213--         Removed
     Introductory text.
    Sec.   493.1213(a)......  Establishment and     Sec.   493.1253(a)
                               verification of
                               performance
                               specifications.
    Sec.   493.1213(b)(1)...  Removed
    Sec.   493.1213(b)(2)...  Establishment and     Sec.  Sec.
                               verification of       493.1253(b)(1) and
                               performance           (2)
                               specifications.
    Sec.   493.1213(b)(2)(i)  Establishment and     Sec.  Sec.
                               verification of       493.1253(b)(1) and
                               performance           (b)(2)
                               specifications.
    Sec.                      Establishment and     Sec.  Sec.
     493.1213(b)(2)(i)(A).     verification of       493.1253(b)(1)(i)(A
                               performance           ) and (b)(2)(i)
                               specifications.
    Sec.                      Establishment and     Sec.  Sec.
     493.1213(b)(2)(i)(B).     verification of       493.1253(b)(1)(i)(B
                               performance           ) and (b)(2)(ii)
                               specifications.
    Sec.                      Establishment and     Sec.
     493.1213(b)(2)(i)(C).     verification of       493.1253(b)(2)(iii)
                               performance
                               specifications.
    Sec.                      Establishment and     Sec.
     493.1213(b)(2)(i)(D).     verification of       493.1253(b)(2)(iv)
                               performance
                               specifications.
    Sec.                      Establishment and     Sec.  Sec.
     493.1213(b)(2)(i)(E).     verification of       493.1253(b)(1)(i)(C
                               performance           ) and (b)(2)(v)
                               specifications.
    Sec.                      Establishment and     Sec.  Sec.
     493.1213(b)(2)(i)(F).     verification of       493.1253(b)(1)(ii)
                               performance           and (b)(2)(vi)
                               specifications.
    Sec.                      Establishment and     Sec.
     493.1213(b)(2)(i)(G).     verification of       493.1253(b)(2)(vii)
                               performance
                               specifications.

[[Page 3645]]

 
    Sec.                      Establishment and     Sec.
     493.1213(b)(2)(ii).       verification of       493.1253(b)(3)
                               performance
                               specifications.
    Sec.   493.1213(c)......  Establishment and     Sec.   493.1253(c)
                               verification of
                               performance
                               specifications.
Equipment maintenance and
 function checks:
    Sec.   493.1215--         Removed
     Introductory text.
    Sec.   493.1215(a)--      Removed
     Title only.
    Sec.   493.1215(a)(1)...  Removed
    Sec.   493.1215(a)(1)(i)  Removed
    Sec.                      Removed
     493.1215(a)(1)(ii).
    Sec.   493.1215(a)(2)--   Removed
     Lead-in only.
    Sec.   493.1215(a)(2)(i)  Maintenance and       Sec.
                               function checks.      493.1254(b)(1)(i)
    Sec.                      Maintenance and       Sec.
     493.1215(a)(2)(ii).       function checks.      493.1254(b)(1)(ii)
    Sec.                      Maintenance and       Sec.
     493.1215(a)(2)(iii).      function checks.      493.1254(b)(1)(ii)
    Sec.   493.1215(b)......  Removed
    Sec.   493.1215(b)(1)...  Removed
    Sec.   493.1215(b)(1)(i)  Removed
    Sec.                      Removed
     493.1215(b)(1)(ii).
    Sec.   493.1215(b)(2)...  Removed
    Sec.   493.1215(b)(2)(i)  Maintenance and       Sec.
                               function checks.      493.1254(b)(2)(i)
    Sec.                      Maintenance and       Sec.
     493.1215(b)(2)(ii).       function checks.      493.1254(b)(2)(ii)
    Sec.                      Maintenance and       Sec.
     493.1215(b)(2)(iii).      function checks.      493.1254(b)(2)(ii)
Calibration and calibration
 verification procedures:
    Sec.   493.1217--         General Provisions--  Sec.  Sec.   493.2;
     Introductory text.        Definitions           493.1255
                               Calibration and
                               calibration
                               verification
                               procedures.
    Sec.   493.1217(a)......  Removed
    Sec.   493.1217(b)--Lead- Removed
     in only.
    Sec.   493.1217(b)(1)...  Calibration and       Sec.   493.1255(a)
                               calibration
                               verification
                               procedures.
    Sec.   493.1217(b)(1)(i)  Calibration and       Sec.
                               calibration           493.1255(a)(1)
                               verification
                               procedures.
    Sec.                      Calibration and       Sec.
     493.1217(b)(1)(ii).       calibration           493.1255(a)(2)
                               verification
                               procedures.
    Sec.                      Calibration and       Sec.
     493.1217(b)(1)(ii)(A).    calibration           493.1255(a)(2)(ii)
                               verification
                               procedures.
    Sec.                      Calibration and       Sec.
     493.1217(b)(1)(ii)(B).    calibration           493.1255(a)(2)(i)
                               verification
                               procedures.
    Sec.                      Calibration and       Sec.
     493.1217(b)(1)(iii).      calibration           493.1255(a)(3)
                               verification
                               procedures.
    Sec.   493.1217(b)(2)...  Calibration and       Sec.   493.1255(b)
                               calibration
                               verification
                               procedures.
    Sec.   493.1217(b)(2)(i)  Calibration and       Sec.
                               calibration           493.1255(b)(1)
                               verification
                               procedures.
    Sec.                      Calibration and       Sec.
     493.1217(b)(2)(ii).       calibration           493.1255(b)(2)
                               verification
                               procedures.
    Sec.                      Calibration and       Sec.
     493.1217(b)(2)(ii)(A).    calibration           493.1255(b)(2)(i)
                               verification
                               procedures.
    Sec.                      Removed
     493.1217(b)(2)(ii)(B).
    Sec.                      Removed
     493.1217(b)(2)(ii)(B)(1
     ).
    Sec.                      Calibration and       Sec.
     493.1217(b)(2)(ii)(B)(2   calibration           493.1255(b)(2)(ii)
     ).                        verification
                               procedures.
    Sec.                      Calibration and       Sec.
     493.1217(b)(2)(ii)(C).    calibration           493.1255(b)(3)
                               verification
                               procedures.
    Sec.                      Calibration and       Sec.
     493.1217(b)(2)(ii)(C)(1   calibration           493.1255(b)(3)(i)
     ).                        verification
                               procedures.
    Sec.                      Calibration and       Sec.
     493.1217(b)(2)(ii)(C)(2   calibration           493.1255(b)(3)(ii)
     ).                        verification
                               procedures.
    Sec.                      Calibration and       Sec.
     493.1217(b)(2)(ii)(C)(3   calibration           493.1255(b)(3)(iii)
     ).                        verification
                               procedures.
    Sec.                      Calibration and       Sec.
     493.1217(b)(2)(ii)(C)(4   calibration           493.1255(b)(3)(iv)
     ).                        verification
                               procedures.
    Sec.   493.1217(b)(3)...  Calibration and       Sec.   493.1255(a)
                               calibration           and (b)
                               verification
                               procedures.
Control procedures:
    Sec.   493.1218.........  Control procedures..  Sec.   493.1256(a)
    Sec.   493.1218(a)......  Removed
    Sec.   493.1218(b)--      Control procedures..  Sec.   493.1256(b),
     Partial removed.                                (c)(1), and (c)(2)
    Sec.   493.1218(b)(1)...  Control procedures..  Sec.
                                                     493.1256(d)(3)(ii)
    Sec.   493.1218(b)(2)...  Control procedures..  Sec.
                                                     493.1256(d)(3)(i)
    Sec.   493.1218(b)(3)...  Control procedures..  Sec.
                                                     493.1256(d)(5)

[[Page 3646]]

 
    Sec.   493.1218(b)(3)(i)  Control procedures..  Sec.
                                                     493.1256(d)(5)
    Sec.                      Control procedures..  Sec.
     493.1218(b)(3)(ii).                             493.1256(d)(5)
    Sec.   493.1218(b)(4)...  Control procedures..  Sec.  Sec.
                                                     493.1256(d)(3)(ii)
                                                     and (d)(3)(iv)
    Sec.   493.1218(b)(5)...  Control procedures..  Sec.   493.1256(h)
    Sec.   493.1218(c)......  Control procedures..  Sec.
                                                     493.1256(d)(8)
    Sec.   493.1218(d)......  Control procedures..  Sec.
                                                     493.1256(d)(10)(i)
    Sec.   493.1218(d)(1)...  Control procedures..  Sec.
                                                     493.1256(d)(10)(ii)
    Sec.   493.1218(d)(2)...  Control procedures..  Sec.
                                                     493.1256(d)(10)(iii
                                                     )
    Sec.   493.1218(e)......  Control procedures..  Sec.   493.1256(f)
    Sec.   493.1218(f)......  Control procedures..  Sec.   493.1256(e)
    Sec.   493.1218(f)(1)...  Control procedures..  Sec.
                                                     493.1256(e)(1)
    Sec.   493.1218(f)(2)...  Control procedures..  Sec.
                                                     493.1256(e)(2)
    Sec.   493.1218(f)(3)...  Control procedures..  Sec.  Sec.
                              Histopathology......   493.1256(e)(3);
                                                    493.1273(a)
    Sec.   493.1218(f)(4)...  Control procedures..  Sec.
                                                     493.1256(e)(4)(5)
Remedial actions:
    Sec.   493.1219--         Corrective actions..  Sec.   493.1282(a)
     Introductory text.                              and (b)
    Sec.   493.1219(a)......  Corrective actions..  Sec.
                                                     493.1282(b)(1)
    Sec.   493.1219(a)(1)...  Corrective actions..  Sec.
                                                     493.1282(b)(1)(i)
    Sec.   493.1219(a)(2)...  Corrective actions..  Sec.
                                                     493.1282(b)(1)(ii)
    Sec.   493.1219(a)(3)...  Corrective actions..  Sec.
                                                     493.1282(b)(1)(iii)
    Sec.   493.1219(b)......  Corrective actions..  Sec.
                                                     493.1282(b)(2)
    Sec.   493.1219(c)......  Test report.........  Sec.   493.1291(h)
    Sec.   493.1219(d)......  Test report.........  Sec.   493.1291(k)
    Sec.   493.1219(d)(1)...  Test report.........  Sec.
                                                     493.1291(k)(1)
    Sec.   493.1219(d)(2)...  Test report.........  Sec.
                                                     493.1291(k)(2)
    Sec.   493.1219(d)(3)...  Retention             Sec.  Sec.
                               requirements.         493.1105(a)(6);
                              Test report.........  493.1291(k)(3)
Quality control records:
    Sec.   493.1221.........  Retention             Sec.   493.1101(e);
                               requirements.
                                                    493.1105(a)(3)(i)
                                                     through (a)(3)(ii);
                              Test systems,         493.1252(b);
                               equipment,
                               instruments,
                               reagents, material,
                               and supplies
                               performance.
                              Establishment and     493.1253(c);
                               verification of
                               performance.
                              Maintenance and       493.1254(a),
                               function checks.      (b)(1)(ii), and
                                                     (b)(2)(ii);
                              Calibration and       493.1255(a) and (b);
                               calibration
                               verification
                               procedures.
                              Control procedures..  493.1256(g);
                              Bacteriology........  493.1261(c);
                              Mycobacteriology....  493.1262(c);
                              Mycology............  493.1263(c);
                              Parasitology........  493.1264(d);
                              Virology............  493.1265(b);
                              Routine chemistry...  493.1267(d);
                              Hematology..........  493.1269(d);
                              Immunohematology....  493.1271(f);
                              Histopathology......  493.1273(f);
                              Cytology............  493.1274(h);
                              Clinical              493.1276(e);
                               Cytogenetics.
                              Histocompatibility..  493.1278(g)
Quality control-specialties
 and subspecialties for
 tests of moderate or high
 complexity; or both:
    Sec.   493.1223.........  Control Procedures..  Sec.  Sec.
                                                     493.1256(a), (b),
                                                     (c), (d)(1), and
                                                     (2);
Microbiology:
    Sec.   493.1225.........  Removed
Bacteriology:
    Sec.   493.1227--         Bacteriology........  Sec.   493.1201
     Introductory text.
    Sec.   493.1227(a)--      Bacteriology........  Sec.   493.1261(a)
     Partially removed.
Bacteriology:
    Sec.   493.1227(a)(1)--   Control procedures..  Sec.  Sec.
     Partially removed.                              493.1256(d)(3)(ii),
                                                     (d)(3)(iv), and
                                                     (e)(1);
                              Bacteriology........  493.1261(a)(1)
    Sec.   493.1227(a)(2)...  Control procedures..  Sec.  Sec.
                                                     493.1256(e)(1) and
                                                     (e)(2);
                              Bacteriology........  493.1261(a)(2)
    Sec.   493.1227(a)(3)...  Bacteriology........  Sec.
                                                     493.1261(a)(3)
    Sec.   493.1227(b)......  Control procedures..  Sec.
                                                     493.1256(e)(1)
    Sec.   493.1227(c)......  Bacteriology........  Sec.   493.1261(b)
    Sec.   493.1227(c)(1)...  Bacteriology........  Sec.
                                                     493.1261(b)(2)
    Sec.   493.1227(c)(2)...  Bacteriology........  Sec.
                                                     493.1261(b)(1)
Mycobacteriology:
    Sec.   493.1229--         Mycobacteriology....  Sec.   493.1202
     Introductory text.

[[Page 3647]]

 
    Sec.   493.1229(a)......  Mycobacteriology....  Sec.   493.1262(a)
    Sec.   493.1229(b)......  Control procedures..  Sec.
                                                     493.1256(e)(3)
    Sec.   493.1229(c)......  Control procedures..  Sec.  Sec.
                                                     493.1256(e)(2);
                              Mycobacteriology....  493.1262(a)
    Sec.   493.1229(d)......  Mycobacteriology....  Sec.  Sec.
                                                     493.1262(b)(1)
                                                     through (b)(3)
Mycology:
    Sec.   493.1231--         Mycology............  Sec.   493.1203
     Introductory text.
    Sec.   493.1231(a)......  Control procedures..  Sec.  Sec.
                                                     493.1256(e)(1) and
                                                     (e)(4)
    Sec.  Sec.   493.1231(b)  Control procedures..  Sec.
                                                     493.1256(e)(1)
    Sec.   493.1231(c)......  Control procedures..  Sec.
                                                     493.1256(e)(2)
    Sec.   493.1231(d)......  Mycology............  Sec.  Sec.
                                                     493.1263(b)(1)
                                                     through (b)(3)
Parasitology:
    Sec.   493.1233--         Parasitology........  Sec.   493.1204
     Introductory text.
    Sec.   493.1233(a)......  Parasitology........  Sec.   493.1264(a)
    Sec.   493.1233(b)......  Parasitology........  Sec.   493.1264(b)
    Sec.   493.1233(c)......  Parasitology........  Sec.   493.1264(c)
Virology:
    Sec.   493.1235--         Virology............  Sec.   493.1205
     Introductory text.
    Sec.   493.1235(a)......  Facilities..........  Sec.  Sec.
                                                     493.1101(b);
                              Test systems,         493.1252(a)
                               equipment,
                               instruments,
                               reagents, material,
                               and supplies.
    Sec.   493.1235(b)......  Virology............  Sec.  Sec.
                                                     493.1265(b);
                              Test records........  493.1283(a)(4)
    Sec.   493.1235(c)......  Virology............  Sec.   493.1265(a)
Diagnostic immunology:
    Sec.   493.1237.........  Removed
Syphilis serology:
    Sec.   493.1239--         Syphilis serology...  Sec.   493.1207
     Introductory text.
    Sec.   493.1239(a)......  Test systems,         Sec.   493.1252(a)
                               equipment,
                               instruments,
                               reagents,
                               materials, and
                               supplies.
    Sec.   493.1239(b)......  Control procedures..  Sec.
                                                     493.1256(d)(3)(iii)
    Sec.   493.1239(c)......  Control procedures..  Sec.  Sec.
                                                     493.1256(a) and
                                                     (d)(3)(ii);
    Sec.   493.1239(d)......  Control procedures..  Sec.   493.1256(f)
    Sec.   493.1239(e)......  Immunohematology....  Sec.   493.1271(b)
General immunology:
    Sec.   493.1241.........  General immunology..  Sec.   493.1208
    Sec.   493.1241(a)......  Control procedures..  Sec.
                                                     493.1256(d)(3)(iii)
    Sec.   493.1241(b)......  Control procedures..  Sec.   493.1256(a)
    Sec.   493.1241(c)......  Control procedures..  Sec.   493.1256(f)
    Sec.   493.1241(d)--Lead- Removed
     in only.
    Sec.   493.1241(d)(1)...  Immunohematology....  Sec.   493.1271(b)
    Sec.   493.1241(d)(2)...  Immunohematology....  Sec.   493.1271(b)
Chemistry:
    Sec.   493.1243.........  Removed
Routine chemistry:
    Sec.   493.1245--         Routine chemistry...  Sec.  Sec.
     Introductory text.                              493.1210; 493.1267
    Sec.   493.1245(a)......  Routine chemistry...  Sec.   493.1267(a)
    Sec.   493.1245(b)......  Routine chemistry...  Sec.   493.1267(b)
    Sec.   493.1245(c)......  Routine chemistry...  Sec.   493.1267(b)
    Sec.   493.1245(d)......  Routine chemistry...  Sec.   493.1267(c)
Endocrinology:
    Sec.   493.1247.........  Endocrinology.......  Sec.   493.1212
Toxicology:
    Sec.   493.1249--         Toxicology..........  Sec.  Sec.
     Introductory text.       Control procedures..   493.1213;
                                                    493.1256(d)(4)
    Sec.   493.1249(a)......  Control procedures..  Sec.
                                                     493.1256(d)(4)(i)
    Sec.   493.1249(b)......  Control procedures..  Sec.
                                                     493.1256(d)(4)(ii)
Urinalysis:
    Sec.   493.1251--         Urinalysis..........  Sec.   493.1211
     Introductory text only.
Hematology:
    Sec.   493.1253.........  Hematology..........  Sec.   493.1215
    Sec.   493.1253(a)......  Hematology..........  Sec.  Sec.
                                                     493.1269(a)(1) and
                                                     (a)(2)
    Sec.   493.1253(b)......  Control procedures..  Sec.   493.1256(d)
    Sec.   493.1253(c)......  Hematology..........  Sec.   493.1269(b)
    Sec.   493.1253(d)......  Hematology..........  Sec.   493.1269(c)
    Sec.   493.1253(d)(1)...  Hematology..........  Sec.
                                                     493.1269(c)(1)
    Sec.   493.1253(d)(2)...  Hematology..........  Sec.
                                                     493.1269(c)(2)
Pathology:
    Sec.   493.1255.........  Removed
Cytology:
    Sec.   493.1257--         Cytology............  Sec.   493.1221
     Introductory text.

[[Page 3648]]

 
    Sec.   493.1257(a)......  Cytology............  Sec.   493.1274(b)
    Sec.   493.1257(a)(1)...  Cytology............  Sec.
                                                     493.1274(b)(1)
    Sec.   493.1257(a)(2)...  Cytology............  Sec.
                                                     493.1274(b)(2)
    Sec.   493.1257(a)(3)...  Cytology............  Sec.
                                                     493.1274(b)(3)
    Sec.   493.1257(a)(4)...  Cytology............  Sec.
                                                     493.1274(e)(4)
    Sec.   493.1257(a)(5)...  Cytology............  Sec.   493.1274(a)
    Sec.   493.1257(b)......  Cytology............  Sec.   493.1274(d)
    Sec.   493.1257(b)(1)...  Cytology............  Sec.  Sec.
                                                     493.1274(d)(2) and
                                                     (d)(2)(iv)
    Sec.   493.1257(b)(2)...  Cytology............  Sec.
                                                     493.1274(d)(2)(iii)
    Sec.   493.1257(b)(3)...  Cytology............  Sec.   493.1274(g)
    Sec.   493.1257(b)(3)(i)  Cytology............  Sec.
                                                     493.1274(d)(2)(i)
    Sec.                      Cytology............  Sec.
     493.1257(b)(3)(ii).                             493.1274(d)(2)(ii)
    Sec.   493.1257(c)......  Cytology............  Sec.
                                                     493.1274(e)(1)
    Sec.   493.1257(c)(1)...  Cytology............  Sec.  Sec.
                                                     493.1274(e)(1)(i)
                                                     through (e)(1)(v),
                                                     and (e)(2)
    Sec.   493.1257(c)(2)...  Cytology............  Sec.
                                                     493.1274(e)(3)
    Sec.   493.1257(c)(3)...  Cytology............  Sec.
                                                     493.1274(d)(1)(i)(B
                                                     )
    Sec.   493.1257(c)(4)...  Cytology............  Sec.
                                                     493.1274(d)(1)
    Sec.   493.1257(c)(4)(i)  Cytology............  Sec.  Sec.
                                                     493.1274(d)(1)(i)
                                                     and (d)(4)
    Sec.                      Cytology............  Sec.
     493.1257(c)(4)(ii).                             493.1274(d)(1)(ii)
    Sec.   493.1257(d)......  Cytology............  Sec.   493.1274(c)
    Sec.   493.1257(d)(1)...  Cytology............  Sec.
                                                     493.1274(c)(1)
    Sec.   493.1257(d)(1)(i)  Cytology............  Sec.
                                                     493.1274(c)(1)(i)
    Sec.                      Cytology............  Sec.
     493.1257(d)(1)(ii).                             493.1274(c)(4)
    Sec.                      Cytology............  Sec.
     493.1257(d)(1)(iii).                            493.1274(c)(1)(ii)
    Sec.   493.1257(d)(2)...  Cytology............  Sec.
                                                     493.1274(c)(2)
    Sec.   493.1257(d)(3)...  Cytology............  Sec.
                                                     493.1274(c)(3)
    Sec.   493.1257(d)(4)...  Cytology............  Sec.  Sec.
                                                     493.1274(c)(5)(i)
                                                     through (c)(5)(vi)
    Sec.   493.1257(d)(5)...  Cytology............  Sec.
                                                     493.1274(c)(6)
    Sec.   493.1257(e)--Lead- Removed
     in only.
    Sec.   493.1257(e)(1)...  Cytology............  Sec.
                                                     493.1274(e)(4)
    Sec.   493.1257(e)(2)...  Cytology............  Sec.
                                                     493.1274(e)(5)
    Sec.   493.1257(f)......  Cytology............  Sec.
                                                     493.1274(e)(6)
    Sec.   493.1257(g)......  Retention             Sec.  Sec.
                               requirements,         493.1105(a)(7)(i)(A
                               Cytology.             ); 493.1274(f)(2)
                                                     through (f)(4)
Histopathology:
    Sec.   493.1259--         Histopathology......  Sec.   493.1219
     Introductory text.
    Sec.   493.1259(a)......  Histopathology......  Sec.   493.1273(a)
    Sec.   493.1259(b)......  Retention             Sec.  Sec.
                               requirements,         493.1105(a)(7)(i)(B
                               Histopathology.       ) and (a)(7)(ii);
                                                     493.1273(b)
    Sec.   493.1259(c)......  Facilities;           Sec.  Sec.
                               Retention             493.1101(e);
                               requirements,         493.1105(a)(7)(iii)
                               Histopathology.       ; 493.1273(b)
    Sec.   493.1259(d)......  Histopathology......  Sec.   493.1273(d)
    Sec.   493.1259(e)......  Histopathology......  Sec.   493.1273(e)
Oral pathology:
    Sec.   493.1261.........  Oral pathology......  Sec.   493.1220
Radiobioassay:
    Sec.   493.1263.........  Radiobioassay.......  Sec.   493.1226
Histocompatibility:
    Sec.   493.1265--         Histocompatibility..  Sec.   493.1227
     Introductory text.
    Sec.   493.1265(a)......  Histocompatibility..  Sec.   493.1278(f)
    Sec.   493.1265(a)(1)...  Histocompatibility..  Sec.
                                                     493.1278(e)(2)
    Sec.   493.1265(a)(1)(i)  Histocompatibility..  Sec.
                                                     493.1278(e)(2)(i)
    Sec.                      Histocompatibility;   Sec.  Sec.
     493.1265(a)(1)(ii).       Procedure manual.     493.1278(e)(1);
                                                     493.1251(b)(3)
    Sec.                      Histocompatibility..  Sec.
     493.1265(a)(1)(iii).                            493.1278(e)(2)(ii)
    Sec.                      Procedure manual....  Sec.  Sec.
     493.1265(a)(1)(iv).                             493.1251(b)(3) and
                                                     (b)(13)
    Sec.   493.1265(a)(2)...  Histocompatibility..  Sec.   493.1278(f)
    Sec.   493.1265(a)(2)(i)  Histocompatibility..  Sec.
                                                     493.1278(f)(2)
    Sec.                      Histocompatibility..  Sec.  Sec.
     493.1265(a)(2)(ii).                             493.1278(d)(4)
                                                     through (d)(5)
    Sec.   493.1265(a)(3)--   Removed
     Lead-in only.
    Sec.   493.1265(a)(3)(i)  Test systems,         Sec.   493.1252(b);
                               equipment,
                               instruments,
                               reagents,
                               materials, and
                               supplies.
                              Specimen submission,  Sec.
                               handling, and         493.1242(a)(4)
                               referral.
    Sec.                      Histocompatibility..  Sec.
     493.1265(a)(3)(ii).                             493.1278(a)(1)
    Sec.                      Specimen              Sec.  Sec.
     493.1265(a)(3)(iii)--Pa   identification and    493.1232;
     rtially removed.          integrity,            493.1278(a)(2)
                               Histocompatibility;   493.1283(a)(1)
                               Test records.
    Sec.   493.1265(a)(4)...  Histocompatibility..  Sec.
                                                     493.1278(a)(3)
    Sec.   493.1265(a)(5)...  Test systems,         Sec.  Sec.
                               equipment,            493.1252(c)(1)
                               instruments,          through (c)(4)
                               reagents,
                               materials, and
                               supplies.
    Sec.   493.1265(a)(6)...  Histocompatibility..  Sec.   493.1278(b)
    Sec.   493.1265(a)(6)(i)  Histocompatibility..  Sec.
                                                     493.1278(b)(2)

[[Page 3649]]

 
    Sec.                      Histocompatibility..  Sec.
     493.1265(a)(6)(ii).                             493.1278(b)(3)
    Sec.                      Histocompatibility..  Sec.
     493.1265(a)(6)(iii).                            493.1278(b)(5)(v)
    Sec.   493.1265(a)(7)...  Histocompatibility..  Sec.
                                                     493.1278(b)(5)
    Sec.   493.1265(a)(7)(i)  Histocompatibility..  Sec.
                                                     493.1278(b)(5)(i)
    Sec.                      Histocompatibility..  Sec.
     493.1265(a)(7)(ii).                             493.1278(b)(5)(ii)
    Sec.                      Histocompatibility..  Sec.
     493.1265(a)(7)(iii).                            493.1278(b)(5)(iv)
    Sec.                      Histocompatibility..  Sec.
     493.1265(a)(7)(iv).                             493.1278(b)(5)(iii)
    Sec.   493.1265(a)(8)...  Histocompatibility..  Sec.   493.1278(d)
    Sec.   493.1265(a)(8)(i)  Histocompatibility..  Sec.
                                                     493.1278(d)(5)
    Sec.                      Histocompatibility..  Sec.
     493.1265(a)(8)(i)(A).                           493.1278(d)(5)
    Sec.                      Histocompatibility..  Sec.
     493.1265(a)(8)(i)(B).                           493.1278(d)(5)
    Sec.                      Histocompatibility..  Sec.
     493.1265(a)(8)(ii).                             493.1278(d)(3)
    Sec.                      Histocompatibility..  Sec.
     493.1265(a)(8)(ii)(A).                          493.1278(d)(3)
    Sec.                      Test systems,         Sec.   493.1252(b)
     493.1265(a)(8)(ii)(B).    equipment,
                               instruments,
                               reagents,
                               materials, and
                               supplies.
    Sec.   493.1265(a)(9)--   Removed
     Lead-in only.
    Sec.   493.1265(a)(9)(i)  Histocompatibility..  Sec.  Sec.
                                                     493.1278(b)(6) and
                                                     (d)(6)
    Sec.                      Histocompatibility..  Sec.  Sec.
     493.1265(a)(9)(i)(A).                           493.1278(b)(6)(i)
                                                     and (d)(6)(i)
    Sec.                      Histocompatibility..  Sec.  Sec.
     493.1265(a)(9)(i)(B).                           493.1278(b)(6)(ii)
                                                     and (d)(6)(ii)
    Sec.                      Histocompatibility..  Sec.
     493.1265(a)(9)(i)(C).                           493.1278(b)(6)(iii)
    Sec.                      Histocompatibility..  Sec.  Sec.
     493.1265(a)(9)(ii).                             493.1278(c) and
                                                     (e)(3)
    Sec.   493.1265(a)(10)..  Histocompatibility..  Sec.  Sec.
                                                     493.1278(a) and (f)
    Sec.   493.1265(a)(11)..  Immunohematology....  Sec.   493.1271
    Sec.   493.1265(a)(12)..  Histocompatibility..  Sec.
                                                     493.1278(a)(4)
    Sec.   493.1265(a)(13)..  Removed
    Sec.   493.1265(a)(14)..  Histocompatibility..  Sec.
                                                     493.1278(a)(5)
    Sec.   493.1265(b)......  Histocompatibility..  Sec.   493.1278(f)
    Sec.   493.1265(b)(1)...  Histocompatibility..  Sec.
                                                     493.1278(f)(1)
    Sec.   493.1265(b)(2)...  Histocompatibility..  Sec.
                                                     493.1278(f)(1)
    Sec.   493.1265(b)(3)...  Histocompatibility..  Sec.
                                                     493.1278(f)(3)
    Sec.   493.1265(c)......  Histocompatibility..  Sec.  Sec.
                                                     493.1278(a) through
                                                     (c)
    Sec.   493.1265(d)......  Immunohematology....  Sec.   493.1271(b)
Clinical cytogenetics:
    Sec.   493.1267--         Clinical              Sec.   493.1225
     Introductory text.        cytogenetics.
    Sec.   493.1267(a)......  Cytogenetics........  Sec.   493.1276(c)
    Sec.   493.1267(b)......  Cytogenetics........  Sec.  Sec.
                                                     493.1276(b)(1)
                                                     through (b)(3)
    Sec.   493.1267(c)......  Cytogenetics........  Sec.   493.1276(a)
    Sec.   493.1267(d)......  Cytogenetics........  Sec.   493.1276(d)
Immunohematology:
    Sec.   493.1269--         Immunohematology....  Sec.   493.1217
     Introductory text.
    Sec.   493.1269(a)......  Immunohematology....  Sec.
                                                     493.1271(a)(1)
    Sec.   493.1269(b)......  Immunohematology....  Sec.
                                                     493.1271(a)(2)
    Sec.   493.1269(c)......  Immunohematology....  Sec.
                                                     493.1271(a)(3)
    Sec.   493.1269(d)......  Immunohematology....  Sec.   493.1271(a)
Transfusion services and
 bloodbanking:
    Sec.   493.1271--         Requirements for      Sec.   493.1103;
     Partially removed.        transfusion           Sec.   493.1449(b)
                               services and          and (q)
                               Subpart M.
Immunohematological
 collection, processing,
 dating periods, labeling
 and distribution of blood
 and blood products:
    Sec.   493.1273--         Immunohematology....  Sec.   493.1271(b)
     Introductory text.
    Sec.   493.1273(a)......  Immunohematology....  Sec.   493.1271(b)
    Sec.   493.1273(b)......  Immunohematology....  Sec.   493.1271(b)
    Sec.   493.1273(c)......  Immunohematology....  Sec.   493.1271(b)
    Sec.   493.1273(d)......  Requirements for      Sec.
                               transfusion           493.1103(c)(2)
                               services.
Blood and blood products
 storage facilities:
    Sec.   493.1275(a)......  Immunohematology....  Sec.   493.1271(c)
    Sec.   493.1275(a)(1)...  Immunohematology....  Sec.
                                                     493.1271(c)(1)
    Sec.   493.1275(a)(2)...  Immunohematology....  Sec.
                                                     493.1271(c)(2)
    Sec.   493.1275(b)......  Requirements for      Sec.
                               transfusion           493.1103(c)(1)
                               services.
Arrangement for services:
    Sec.   493.1277.........  Requirements for      Sec.   493.1103(a)
                               transfusion
                               services.
Provision of testing:
    Sec.   493.1279--         Requirements for      Sec.  Sec.
     Partially removed.        transfusion           493.1103(b)
                               services.
Retention of samples of
 transfused blood:
    Sec.   493.1283.........  Immunohematology....  Sec.   493.1271(d)
Investigation of transfusion
 reactions:
    Sec.   493.1285.........  Requirements for      Sec.  Sec.
                               transfusion           493.1103(d);
                               services;             493.1271(e)(1)and
                               Immunohematology.     (e)(2)

[[Page 3650]]

 
Quality assurance for
 Moderate Complexity
 (including the Subcategory)
 or High Complexity Testing,
 or Any Combination of These
 Tests:
    Sec.   493.1701.........  Introduction;         Sec.  Sec.
                               General laboratory    493.1200; 493.1230;
                               systems; General      493.1239; 493.1240;
                               laboratory systems    493.1241(e);
                               assessment;           493.1249; 493.1250;
                               Preanalytic           493.1289; 493.1290;
                               Systems; Test         493.1299
                               request;
                               Preanalytic systems
                               assessment;
                               Analytic Systems;
                               Analytic systems
                               assessment;
                               Postanalytic
                               Systems;
                               Postanalytic
                               systems assessment.
Patient test management
 assessment:
    Sec.   493.1703--         General laboratory    Sec.  Sec.
     Introductory text.        systems; General      493.1230;
                               laboratory systems    493.1239(a) and
                               assessment;           (b); 493.1240;
                               Preanalytic           493.1249(a) and
                               Systems;              (b); 493.1290;
                               Preanalytic systems   493.1299(a) and (b)
                               assessment;
                               Postanalytic
                               Systems;
                               Postanalytic
                               systems assessment.
    Sec.   493.1703(a)......  Preanalytic systems   Sec.  Sec.
                               assessment.           493.1249(a) and (b)
    Sec.   493.1703(b)......  Preanalytic systems   Sec.  Sec.
                               assessment.           493.1249(a) and (b)
    Sec.   493.1703(c)......  Preanalytic systems   Sec.  Sec.
                               assessment.           493.1249(a) and (b)
    Sec.   493.1703(d)......  Postanalytic systems  Sec.  Sec.
                               assessment.           493.1299(a) and (b)
    Sec.   493.1703(e)......  Test Report;          Sec.  Sec.
                               Postanalytic          493.1291(a), (g),
                               systems assessment.   and (h);
                                                     493.1299(a) and (b)
    Sec.   493.1703(f)......  Facilities;           Sec.  Sec.
                               Postanalytic          493.1101(e)
                               systems assessment.   493.1299(a) and (b)
Quality control assessment:
    Sec.   493.1705--         Analytic Systems;     Sec.  Sec.
     Introductory text.        Analytic system       493.1250;
                               assessment.           493.1289(a) and (b)
    Sec.   493.1705(a)......  Analytic system       Sec.  Sec.
                               assessment.           493.1289(a) and (b)
    Sec.   493.1705(b)......  Analytic system       Sec.  Sec.
                               assessment.           493.1289(a) and (b)
    Sec.   493.1705(c)......  Analytic system       Sec.  Sec.
                               assessment;           493.1289(a) and
                               Postanalytic          (b); 493.1299(a)
                               systems assessment.   and (b)
Proficiency testing
 assessment:
    Sec.   493.1707.........  General laboratory    Sec.  Sec.
                               systems; Evaluation   493.1230;
                               of proficiency        493.1236(a)(1);
                               testing; General      493.1239(a) and (b)
                               laboratory systems
                               assessment.
Comparison of test results:
    Sec.   493.1709
    Sec.   493.1709(a)......  Comparison of test    Sec.   493.1281(a)
                               results.
    Sec.   493.1709(b)......  Evaluation of         Sec.
                               proficiency testing.  493.1236(c)(1)
Relationship of patient
 information to patient test
 results:
    Sec.   493.1711--         Comparison of test    Sec.  Sec.
     Introductory text.        results; Analytic     493.1281(b);
                               systems assessment.   493.1289(a) and (b)
    Sec.   493.1711(a)......  Comparison of test    Sec.
                               results.              493.1281(b)(1)
    Sec.   493.1711(b)......  Comparison of test    Sec.
                               results.              493.1281(b)(2)
    Sec.   493.1711(c)......  Comparison of test    Sec.
                               results.              493.1281(b)(3)
    Sec.   493.1711(d)......  Comparison of test    Sec.
                               results.              493.1281(b)(4)
    Sec.   493.1711(e)......  Comparison of test    Sec.  Sec.
                               results; Analytic     493.1281(b)(5);
                               systems assessment.   493.1289(a) and (b)
Personnel assessment:
    Sec.   493.1713.........  Personnel competency  Sec.  Sec.
                               assessment            493.1235;
                               policies; General     493.1239(a) and (b)
                               laboratory systems
                               assessment.
Communications:
    Sec.   493.1715.........  Communications;       Sec.  Sec.
                               General laboratory    493.1234;
                               systems assessment.   493.1239(a) and (b)
Complaint investigations:
    Sec.   493.1717.........  Complaint             Sec.  Sec.
                               investigations;       493.1233;
                               General laboratory    493.1239(a) and (b)
                               systems assessment.
Quality assurance review
 with staff:
    Sec.   493.1719.........  General laboratory    Sec.  Sec.
                               systems assessment;   493.1239(b) and
                               Preanalytic systems   (c); 493.1249(b)
                               assessment;           and (c);
                               Analytic systems      493.1289(b) and
                               assessment;           (c); 493.1299(b)
                               Postanalytic          and (c)
                               systems assessment.
Quality assurance records:
    Sec.   493.1721.........  Retention             Sec.  Sec.
                               requirements;         493.1105(a)(5) and
                               General laboratory    (b); 493.1239(c);
                               systems assessment;   493.1249(c);
                               Analytic systems      493.1289(c);
                               assessment.           493.1299(c)
------------------------------------------------------------------------


[[Page 3651]]

IV. Analysis and Responses to Public Comments

    We received numerous comments on the final rule with comment period 
published on February 28, 1992 in the Federal Register. These comments 
were from State agencies, proficiency testing programs, professional 
organizations, the Clinical Laboratory Improvement Advisory Committee 
(CLIAC), laboratories, physicians, and the general public. Summaries of 
the public comments received and our responses to those comments are 
set forth below.

Subpart I--Proficiency Testing Programs for Tests of Moderate 
Complexity (Including the Subcategory), High Complexity, or Any 
Combination of These Tests

    We received a number of comments on the topic of proficiency 
testing. We intend to publish a notice of proposed rulemaking 
addressing proficiency testing issues in more detail in the future. We 
have, however, determined that it would be appropriate to include in 
this final rule a change that we believe is necessary to improve the 
operation of the CLIA proficiency testing program, related to the 
percentage of required agreement among participant or reference 
laboratories. Thus, we are addressing only one of the changes requested 
by the commenters and recommended by the CLIAC.
    Specific comments received and response to comments regarding 
subpart I are set forth below.
    Comment: A few commenters, professional organizations, and 
proficiency testing programs expressed their concerns over the change 
to a 90 percent consensus requirement to be reached before a 
proficiency testing sample could be graded. Commenters felt there 
should be a grade assigned to their samples. One commenter stated that 
their laboratory paid for samples, so grading should be required. 
Proficiency testing programs had similar opinions. The CLIAC 
recommended reducing the consensus required for grading proficiency 
testing challenges to decrease the number of ungradeable samples as 
ungraded proficiency testing is not effective in assisting laboratories 
in their quality assessment of test performance.
    Response: We agree with the commenters and are changing the 
percentage of required agreement among participant or referee 
laboratories to 80 percent in the specialties and subspecialties where 
90 percent agreement was previously required.

Subpart J--Patient Test Management for Moderate Complexity (Including 
the Subcategory), High Complexity, or Any Combination of These Tests

    Following publication of the final rule with comment period, we 
received approximately 150 comments regarding subpart J. The comments 
were in response to the requirements for specimen submission and 
handling; test requisition including oral requests and authorized 
persons; and test records and test reports, including confidentiality 
and referral of specimens. The majority of the commenters disagreed 
with some portion of the requirements and some commenters requested 
clarification of certain requirements while others offered specific 
revised language.
    Specific comments received and responses to comments regarding 
subpart J are set forth below.
    Comment: A number of State agencies disagreed with our removal of 
the requirement that laboratories comply with applicable Federal, 
State, and local laws.
    Response: We agree with the commenters and are reinstating the 
requirement now at Sec.  493.1101(c). As part of the partnering 
relationship with State agencies and local governments, the 
reinstatement of this requirement will allow us to support a State or 
local government that seeks to protect the public from actions it finds 
would be detrimental to public health.
    Comment: Some commenters disagreed with requiring written 
authorization for oral test requests, describing the difficulties that 
this requirement causes.
    Response: We acknowledge that when a laboratory asks that an oral 
request for patient testing be followed with a written request, there 
is no guarantee that one will be received. On January 19, 1993, we 
published a technical correction in the Federal Register (58 FR 5215) 
and (58 FR 5229) that amended the requirement formerly at Sec.  
493.1105. This requirement, now at Sec.  493.1241(b), states that oral 
requests for laboratory tests are permitted only if the laboratory 
requests written or electronic authorization for testing within 30 days 
of the oral request and documents the efforts made to obtain a written 
or electronic authorization.
    Comment: We received several comments recommending information the 
laboratory should solicit and obtain on the test requisition. 
Specifically, the commenters believe the age and sex of the patient, 
time of specimen collection, and the specimen source should be included 
since they are pertinent to either how the laboratory processes the 
specimen and/or how the test results are interpreted.
    Response: We agree with the commenters. The requirement, formerly 
at Sec.  493.1105(f), requires the laboratory to ensure that the 
requisition or test authorization includes any additional information 
relevant and necessary for accurate and timely testing and result 
reporting (for clarity, we are adding ``interpretation'' if applicable 
to this requirement). The requirement, now at Sec.  493.1241(c)(3), 
specifies that the laboratory must request the patient's sex and age or 
date of birth as normal values and interpretation of test results are 
often dependent on this information. Concurrently, we are redesignating 
age or date of birth requirements, formerly at Sec.  493.1105(e), for 
Pap smear requisitions to test requests (now at Sec.  493.1241(c)(3)). 
The time of specimen collection must also be requested when it is 
relevant for the testing to be performed. For example, this information 
is important when interpreting the results of peak and trough 
therapeutic drug assays. In addition, we are requiring that specimen 
source, when appropriate, be solicited on the test requisition. 
Specimen handling, preservation, and preparation (for example, use of 
proper transfer media, inoculation of media in microbiology and 
clinical cytogenetics, and the application of appropriate normal values 
reported with patient test results) are dependent on the origin of the 
specimen. Therefore, we are including specimen source, when 
appropriate, as part of the laboratory's submission, handling, and 
referral procedures (now at Sec.  493.1242(a)(3)). We are also 
requiring specimen source to be included on the test report if 
warranted (now at Sec.  493.1291(c)(5)). This routine laboratory 
practice was inadvertently omitted from the final rule with comment 
period.
    Comment: One organization representing members of the laboratory 
community objected to the amount of information that a laboratory must 
have on the test requisition, specifically the information that is 
needed when submitting a Pap smear. The organization stated that 
laboratories do not have access to patient records and are dependent on 
the authorized person ordering the test to provide this information. 
The organization agreed the information was important but assumed we 
would prohibit testing if all information was not obtained by the 
laboratory.
    Response: We agree with the commenter that the information being 
requested is important. Therefore, we are retaining the test request

[[Page 3652]]

requirements formerly at Sec.  493.1105, (now at Sec.  493.1241(c)) as 
relevant information necessary for proper test performance and 
interpretation. The test requisition requirements do not prohibit 
laboratories from performing the testing if the requested information 
is missing. Although we expect laboratories to obtain this information 
when possible, the potential negative impact of the missing information 
on the test results may be addressed or noted on the report.
    Comment: One State health department requested modification of the 
requirement for recording the time of specimen receipt into the 
laboratory, stating we should require the time of receipt only if it is 
pertinent to sample integrity, test method, or procedure.
    Response: We disagree with the commenter. Recording the date and 
time of specimen receipt enables the laboratory to determine the 
elapsed time between specimen receipt and reporting of patient test 
results. It also provides a mechanism to monitor transportation times 
for specimens referred to the laboratory. Therefore, we are retaining 
this requirement formerly at Sec.  493.1107(b) (now at Sec.  
493.1242(b)).
    Comment: One commenter stated the final rule with comment period 
did not require a person's name or unique identifier on the test 
report.
    Response: We agree with the commenter that the final rule with 
comment period did not specifically require a patient's name or unique 
identifier as part of the test report formerly at Sec.  493.1109. 
Therefore, we are adding at Sec.  493.1291(c)(1), a requirement for the 
laboratory report to include the patient's name with an identification 
number, or a unique patient identifier and identification number to 
ensure positive patient identification. The patient's name alone is not 
a unique identifier, and when used on the test report, the patient's 
name must be accompanied by an identification or accession number. When 
a patient's name is not used for confidentiality purposes, or when the 
identity of the person is not known, a unique patient identifier must 
be submitted with the specimen. The laboratory must also use an 
identification number. In reviewing the report requirements formerly at 
Sec.  493.1109(b), interpretation was omitted. Therefore, we are adding 
interpretation to the test report requirements at Sec.  493.1291(c)(6) 
for those test results that require supplemental information.
    Comment: Some commenters disagreed with requiring the name and 
address of the laboratory performing the test on the test report. They 
believed that too much information would make the report crowded and 
confusing. Another comment received from a professional organization 
acknowledged the benefit of this requirement, but stated its 
application to cumulative reports causes disruption of data 
presentation and utility of the report and, in some cases, the 
information cannot reasonably be included.
    Response: We agree the name and address of the laboratory 
performing the test is an essential piece of information that must be 
included on the test report. It provides a contact for the individual 
who requested or is using the test results when additional information 
is needed for result interpretation and patient care. If a laboratory 
determines its reports are crowded or confusing, it has complete 
latitude and responsibility to reorganize the report in a manner that 
will correct the problem as specified formerly at Sec.  493.1703 (now 
at Sec.  493.1299). A laboratory that generates cumulative reports may 
use a single character identifier (for example, an asterisk or 
subscript) to identify a particular reference laboratory that performed 
the test. This information (the name and address of the reference 
laboratory) may be defined on a subsequent page or on the back of the 
report. Laboratories may develop other formats to meet this 
requirement. However, we are retaining the requirement formerly at 
Sec.  493.1109(b) (now at Sec.  493.1291(c)(2)) to include the name and 
address of the laboratory where the test was performed.
    Comment: One commenter questioned the appropriateness of 
maintaining test records in the patient's chart or medical record.
    Response: The CLIA regulation does not preclude laboratories from 
storing test records in a patient's chart or medical record; however, 
records must include the following:
    [sbull] Test analysis (including instrument printouts, if 
applicable).
    [sbull] Identity of the personnel performing the test.
    To retain this type of information in a patient's chart or medical 
record may be cumbersome and impractical for QA activities; however, it 
is at the discretion of the laboratory.
    Comment: One commenter questioned whether computer records of 
reports are acceptable in lieu of paper files.
    Response: The requirement formerly at Sec.  493.1109(h) specifies 
that all test reports or an exact duplicate of each test report must be 
maintained by the laboratory in a manner that permits ready 
identification and timely accessibility. The information contained on 
the test report may be manually written, generated by an electronic 
system, maintained on microfilm, or any other means, provided it 
contains all of the information that was on the original test report. 
Therefore, we are deleting the reference to ``exact duplicate'' that 
was contained in the former Sec.  493.1109(h), and amending the 
language now at Sec.  493.1291(j) to clarify that the laboratory must 
be able to retrieve a copy of the original report. We are also making a 
conforming change in the retention requirement for test reports (now at 
Sec.  493.1105(a)(6)).
    Comment: Many commenters stated that the removal of the subpart on 
laboratory information systems (LIS) was inappropriate and not logical 
considering the current and future direction of collection and 
dissemination of laboratory data. Other commenters indicated that the 
current method of reporting patient results and the laboratory computer 
system was overlooked.
    Response: We agree with all of the commenters and are addressing 
some of the commenters' concerns pertaining to electronic patient and 
testing information by doing the following:
    [sbull] Adding a requirement at Sec.  493.1101(e) for laboratories 
to store and maintain records in a manner that ensures proper 
preservation. Proper storage of patient records that are collected in a 
LIS is essential for record preservation and accurate recall of patient 
information. Without proper storage and maintenance of records, the 
timeframes, identification, and the accessibility of records will not 
be possible.
    [sbull] Incorporating a requirement at Sec.  493.1241(e) for 
laboratories using LIS to ensure that the requisition information is 
accurately transcribed or entered. The laboratory may establish its own 
mechanism to meet this requirement, possibly through random checks or 
representative sampling of LIS patient testing information verified 
against that submitted on the original test request.
    [sbull] Adding a requirement at Sec.  493.1291(a) that requires 
laboratories to ensure patient test results are accurately and reliably 
sent from the point of data entry to the final report's destination in 
a timely manner. We are providing frequently encountered reporting 
scenarios that must be reviewed by the laboratory to ensure the 
accuracy and reliability of the transmitted patient result information.
    [sbull] Requiring at Sec.  493.1291(c) that the date of the test 
report be identified on the report. This date must be maintained as the 
date testing results

[[Page 3653]]

were generated as a final report and must not change on copies reported 
at a later date.
    The above requirements are intended to respond in part to the 
commenters' requests. We intend to publish, at a later date, a rule 
specific to laboratory information systems. For example, requirements 
for the establishment and verification of system programs, system 
security, system and device maintenance, system operator functions and 
responsibilities, and system backups.
    Comment: One commenter was concerned about limited record storage 
space on-site and asked if off-site storage of records would be 
acceptable provided the laboratory was able to produce these records 
during an inspection.
    Response: Records may be stored at a place of the laboratory's 
choosing providing the storage is appropriate and the laboratory can 
produce the documents within a reasonable time during the course of an 
inspection as required at Sec.  493.1773(c).
    Comment: Several commenters disagreed with the requirement to 
retain records for a minimum of 2 years or 5 years, depending upon the 
type of record. A professional organization questioned whether 
instrument printouts must be retained for 2 years if appropriate data 
are saved in a retrievable manner. Other commenters felt that 3 months, 
and, in one case, 6 months, would be sufficient time to retain 
instrument printouts.
    Response: We believe all records related to testing, for example, 
records of test requests, patient test records including, if 
applicable, instrument printouts, and copies of test reports are 
essential for the ongoing QA reviews performed by the laboratory. 
Instrument printouts are test records and are sometimes used as test 
reports and for these reasons must be retained for the appropriate 
length of time unless all information is duplicated in another record 
system. Additionally, CLIA requires biennial certification that 
includes an inspection of the laboratory's activities for compliance 
with CLIA requirements by either an on-site inspection of the 
laboratory or a self-assessment inspection through use of the Alternate 
Quality Assessment Survey (AQAS). These inspections require a review of 
the testing performed by the laboratory since the previous biennial 
inspection. Two years is the minimum amount of time records must be 
retained to ensure that they are available for review at inspection. 
However, we are clarifying the record retention requirements for 
immunohematology and blood and blood products formerly at Sec.  
493.1107 introductory text and Sec.  493.1221 (now at Sec.  
493.1105(a)(3)(ii)) and formerly at Sec.  493.1109 introductory text 
(now at Sec.  493.1105(a)(6)(i)) to ensure consistency with the FDA 
requirements for these types of records.

Subpart K--Quality Control for Tests of Moderate Complexity (Including 
the Subcategory), High Complexity, or Any Combination of These Tests

    In the final rule with comment period, the QC rules are located in 
subpart K and include the general QC requirements and specific QC 
requirements for each specialty and subspecialty of testing. A phase-in 
period provided less stringent general QC requirements for unmodified 
moderate complexity tests approved by the FDA through the premarket 
notification 510(k) or premarket approval (PMA) process.
    Following publication of the final rule with comment period, we 
received approximately 1,030 comments. Of these comments, 280 were 
directed at the general QC requirements, 67 pertained to the specialty 
and subspecialty QC requirements, and approximately 680 pertained to 
cytology and histopathology requirements. The majority of the comments 
disagreed with some portion of the requirements, indicating that the 
final rule with comment period was either too restrictive or too 
lenient. Some commenters requested clarification of certain 
requirements, while others offered specific revised language. A few 
comments agreed with the final rule with comment period, while others 
indicated the requirements had either been misinterpreted or misread. 
We addressed some of the commenters' issues in a technical correction 
published on January 19, 1993 in the Federal Register (58 FR 5215).
    In evaluating the comments and considering the types of revisions 
to make in this subpart, we obtained recommendations from the CLIAC and 
consulted with various professional organizations and laboratory 
personnel. In September 1996, we participated in public discussions at 
a 2-day meeting in Atlanta, Georgia. At the public meeting, 
manufacturers, laboratory organizations, and State representatives made 
presentations concerning QC principles, control materials and systems, 
manufacturers' recommendations, costs associated with control testing, 
and personnel implications. Their recommendation was to make changes to 
accommodate new technology. Our changes in this final rule are based on 
the advice and comments we received.
    Specific comments and response to comments regarding subpart K are 
set forth below.
    Comment: We received mixed comments concerning the general QC 
requirements. Some commenters felt the QC requirements were burdensome 
and would increase the cost of testing and asked that these 
requirements be deleted or revised. Conversely, some commenters agreed 
with the requirements, indicating that QC is absolutely essential to 
producing accurate test results and is good laboratory practice. Others 
stated the requirements of subpart K were both reasonable and 
attainable. A few commenters requested further clarification.
    Response: We agree with the comments that QC procedures are 
essential to good laboratory practice and production of accurate test 
results. Control procedures verify that the patient results are 
substantially unaffected by day-to-day variation caused by the test 
system, environment, or operator. While the requirement for 
implementing QC may initially increase the cost of testing in some 
settings, it may decrease the long term cost as improved accuracy and 
reliability of testing reduces the need for retesting and unnecessary 
procedures or treatments.
    Comment: A manufacturer's organization requested that Sec.  
493.1202(c) be revised to include those products not subject to the FDA 
clearance process to allow laboratories performing these tests to meet 
the phase-in QC requirements.
    Response: We agree that the regulation needs to be revised to 
include these products, and provisions addressing these products were 
added in the revisions to the regulations published in the January 19, 
1993 technical corrections (58 FR 5215). Since these products are not 
evaluated by the FDA, they could not be included under Sec.  
493.1202(c) but were added to Sec.  493.1202(b) and subject to all 
applicable standards of subpart K.
    Comment: Comments were divided concerning the phase-in of the 
general QC requirements. Some commenters agreed with the phase-in while 
others were opposed. Some commenters felt that following manufacturers' 
instructions should be sufficient to meet the CLIA QC requirements. 
Others expressed concern that FDA would not complete the review and 
approval of manufacturers' QC instructions by September 1, 1994. Most 
commenters opposed the phase-in provision. Some

[[Page 3654]]

commenters were concerned that manufacturers' QC protocols cleared by 
the FDA might be less stringent than the CLIA QC requirements. Other 
commenters disagreed with having two sets of general QC requirements, 
and other commenters were confused about the phase-in requirements and 
requested clarification.
    Response: We implemented a phase-in of the general QC requirements 
to allow previously unregulated laboratories performing only FDA-
approved or cleared, unmodified, and moderate complexity testing 
sufficient time to implement effective QC programs. During the phase-
in, the FDA was to establish a process to review and clear 
manufacturers' QC instructions for CLIA QC purposes. Under this 
process, laboratories could meet certain CLIA QC requirements by 
following the FDA-approved manufacturers' QC instructions. On four 
occasions, we extended the phase-in of the general QC requirements that 
are currently in effect until December 31, 2002. However, because the 
CLIA program is user fee funded, we decided it would be prudent to wait 
until the phase-in period ended before implementing the FDA QC review. 
This afforded us the survey experience necessary to determine whether 
an additional FDA review would be of benefit to laboratories. We 
realized through our experience inspecting laboratories that an 
additional FDA review would not be of such benefit. Therefore, in this 
final rule, we are eliminating the phase-in requirements and 
establishing minimum general quality system requirements applicable to 
all nonwaived testing, regardless of complexity. In addition, we are 
removing all references to the FDA QC clearance process that was not 
implemented. However, we agree with the commenters that it is essential 
for laboratories to perform testing according to the manufacturers' 
test system instructions as required formerly at Sec.  493.1202(c)(1) 
(now at Sec.  493.1252(a)).
    Comment: A few comments were received in response to the 
environmental and safety requirements at Sec.  493.1204. Some 
commenters indicated that the requirements were too lenient. Others 
were opposed to exempting moderate complexity testing from the 
requirements at Sec.  493.1204 during the phase-in, stating that all 
laboratories should be subject to these requirements.
    Response: We agree with the commenters and therefore are retaining 
the requirement formerly at Sec.  493.1204 (now at Sec.  493.1101, 
subpart J) and applying it to both moderate and high complexity 
testing. In addition, we are providing some flexibility to the 
requirement formerly at Sec.  493.1204(b) (now at Sec.  493.1101(d)) 
that requires laboratories to post safety precautions. The revisions 
now require that safety procedures be accessible rather than posted.
    Comment: We received several comments concerning the requirements 
at Sec.  493.1205. Most commenters opposed the requirement prohibiting 
the use of expired reagents. One commenter requested clarification of 
Sec.  493.1205(c)(1) that requires the laboratory to define criteria 
for reagent and specimen storage conditions.
    Response: We understand the concerns expressed regarding the use of 
rare and expensive reagents and materials beyond their expiration 
dates. However, the manufacturer has the responsibility for 
establishing expiration dates that ensure the reagents and materials 
will perform properly when used for patient testing. In addition, any 
changes in the labeling of in-vitro diagnostics must comply with Food, 
Drug, and Cosmetic Act requirements. Therefore, we are not making any 
revisions to the requirement formerly at Sec.  493.1205(e)(1) (now at 
Sec.  493.1252(d)) prohibiting the use of expired reagents and other 
materials.
    In regard to licensed biological and blood products, any exceptions 
to dating requirements must be granted by the FDA in the form of an 
amendment to the product license. In this final rule, we are 
consolidating all requirements pertaining to the immunohematological 
testing and distribution of blood and blood products (now at Sec.  
493.1271(b)).
    We are adding language to the requirement formerly at Sec.  
493.1205(c)(1) to clarify how the laboratory establishes and uses its 
criteria for storing reagents and patient specimens. The requirement 
now at Sec.  493.1252(b), states that the laboratory must define 
criteria for those conditions in the manufacturer's test system 
instructions, when available, that are essential for proper storage of 
reagents and specimens, and accurate and reliable test system operation 
and test result reporting. The criteria must be consistent with the 
manufacturers' instructions, if provided. These conditions must be 
monitored, documented, and include (1) water quality; (2) temperature; 
(3) humidity; and (4) electrical tolerances.
    Comment: One commenter agreed with the requirements at Sec.  
493.1211, Procedure manual. Another commenter suggested that the 
procedure manual requirements be deleted. Two commenters opposed 
permitting the use of the manufacturer's package insert to satisfy the 
requirements at Sec. Sec.  493.1211(b)(1) through 493.1211(b)(13). 
Another commenter suggested that laboratories be required to retain 
each procedure's original specifications and instructions for use as 
provided by the manufacturer, and maintain a list of any alterations or 
changes in the procedure manual.
    Response: We disagree with the commenter who requested that the 
procedure manual requirements be deleted. All laboratories must 
maintain and follow procedure manual instructions in order to provide 
uniform patient testing. Therefore, we are retaining the requirements 
for a procedure manual now at Sec.  493.1251. Laboratories may use the 
manufacturer's test system instructions to meet many of the procedure 
manual requirements, but must supplement them with any laboratory-
specific information related to its testing and reporting practices. 
Examples are the laboratory's procedures for reporting patient test 
results, including panic values or alert values, corrective actions to 
follow when test systems become inoperable, and criteria for specimen 
referral. The use of the manufacturer's test system instructions to 
meet many of the procedure manual requirements is permitted to ensure 
that laboratories follow the manufacturer's instructions for patient 
testing and to minimize the burden on laboratories in developing 
procedure manuals.
    For clarity and consistency, we are reiterating the requirements 
formerly at Sec. Sec.  493.1103(a) and 493.1211(b)(14) (now at 
Sec. Sec.  493.1242 and 493.1251) that the laboratory have written 
policies and procedures for specimen submission. In addition, we 
included language now at Sec.  493.1251(b)(13) to clarify the use of 
laboratory information systems for entering patient test results.
    In addition, we agree with the commenter that laboratories must 
have copies of test procedures. Therefore, we are retaining the 
requirement now at Sec.  493.1251(e) that laboratories must maintain a 
copy of the procedure with the dates of initial use and discontinuance 
for 2 years after a procedure is no longer used.
    Comment: Several commenters opposed the requirement at Sec.  
493.1211 for the director to approve, date, and sign the procedure 
manual, approve any change in procedure, or re-approve the manual 
should there be a change in directorship. One commenter suggested that 
the requirement be revised to state each procedure must be approved by 
the director before patient testing.
    Response: The director is the individual ultimately responsible for 
the operation and administration of the

[[Page 3655]]

testing facility and is therefore responsible for authorizing all 
testing procedures and any alterations or revisions of these 
procedures. If a change in directorship occurs, re-approval of the 
manuals by the new director is necessary since he or she assumes 
responsibility for all testing procedures and any alterations or 
revisions of the procedures. We agree with the comment stating that 
each procedure should be approved by the director before patient 
testing. Therefore, we are revising the requirement formerly at Sec.  
493.1211(d) (now at Sec.  493.1251(d)) to specify that the director 
reviews each procedure and change in procedure before use. We are also 
emphasizing that we do not expect laboratories to suspend testing for 
those procedures already in use that may not have been approved before 
patient testing. However, effective April 24, 2003, all alterations in 
current procedures and all newly implemented procedures must be 
reviewed and signed by the director before use.
    In addition, we are revising the requirement formerly at Sec.  
493.1211(e) (now at Sec.  493.1251(d)) to include the provision that 
requires procedures to be re-approved if the directorship changes. 
Section 493.1251(d) now states, ``procedures and changes in procedures 
must be approved, signed, and dated by the current laboratory director 
before use.'' If the directorship changes, the current director would 
not be expected to suspend testing to review the procedures in use or 
changes to procedures approved by the previous director. However, the 
current director must review all procedures in use by the laboratory in 
a timely manner.
    Comment: Approximately one third of the comments received disagreed 
with Sec.  493.1213, Establishment and verification of method 
performance specifications. Some individuals opposed verifying the 
manufacturer's performance specifications for those methods cleared by 
FDA as meeting certain CLIA requirements for QC. One commenter 
disagreed with the requirement to establish performance specifications 
for those methods developed in-house, modified by the laboratory, or 
not cleared by FDA as meeting certain CLIA QC requirements. Another 
individual suggested that the standard be retroactive and apply to all 
test methods. One commenter asked that this standard be revised to 
state, ``The provisions of this section are not retroactive for 
previously unregulated laboratories. Previously unregulated 
laboratories are not required * * *.''
    Response: We understand the commenters' concerns about the time and 
resources necessary to establish or verify performance specifications. 
However, these requirements ensure that the laboratory has either 
established test system performance specifications or verified that it 
can obtain the manufacturer's performance specifications in the 
laboratory's environment using the laboratory's testing personnel. In 
addition, establishment or verification of performance specifications 
are integral to the laboratory's establishment of appropriate and 
effective QC and calibration protocols. These protocols must include 
descriptions of the numbers, types, and concentrations of all 
calibration and control materials, as well as the performance 
intervals. Calibration and control protocols based on unverified 
performance specifications could result in poorly controlled and 
inaccurate testing. In the interest of establishing appropriate 
calibration and control practices and improving the reliability, 
accuracy, and usefulness of patient testing, we are retaining the 
requirements formerly at Sec.  493.1213, and are now applying them to 
nonwaived testing at Sec.  493.1253.
    Laboratories employing methods (not modified by the laboratory) 
that have manufacturer-established performance specifications must 
demonstrate before reporting patient test results that they can obtain 
performance specifications for accuracy, precision, and reportable 
range of test results for the test system, comparable to those 
established by the manufacturer. The laboratory director must decide 
the extent to which these performance specifications are verified based 
on the method, testing conditions, and personnel performing the test.
    In addition, we are clarifying when a laboratory must establish 
test system performance specifications (for example, laboratories using 
a test system in which the manufacturer does not provide performance 
specifications) now at Sec.  493.1253(b)(2). Laboratories must, before 
reporting patient test results, establish, as applicable, performance 
specifications for the following performance characteristics: (1) 
Accuracy; (2) precision; (3) analytical sensitivity; (4) analytical 
specificity, including interfering substances; (5) reportable range of 
test results for the test system; (6) reference intervals (normal 
ranges); and (7) any other performance characteristic required for test 
performance.
    Section 493.1253(b)(1) uses the term ``FDA-cleared or approved test 
system'' as defined (at Sec.  493.2, Definition) in the November 9, 
1997 revisions to the Food, Drug and Cosmetic Act (Pub. L. 105-115), to 
mean a test system cleared or approved by the FDA through either the 
premarket notification (510(k)) or premarket approval (PMA) process for 
in-vitro diagnostic use. This includes test systems exempt from FDA 
premarket clearance or approval.
    Regulations do not have retroactive effect. The CLIA requirement's 
effective date became applicable to newly regulated laboratories on 
September 1, 1992. Those laboratories that were subject to regulations 
prior to this September 1, 1992 effective date were already required to 
validate test procedures under former Federal regulations before the 
CLIA requirements were implemented. This rule does not have a 
retroactive effect. Laboratories performing unmodified moderate 
complexity tests cleared or approved by the FDA are not required to 
retroactively verify the manufacturer's performance specifications. The 
results of the laboratory's control procedures, proficiency testing 
(required under subpart H) and assessment activities are used to verify 
test performance. However, as of April 24, 2003, laboratories must, 
before testing, either verify or establish performance specifications 
for any new test system.
    Comment: Some commenters expressed approval of the requirements for 
the establishment and verification of a test system's method 
performance specifications before its use, and maintaining records of 
this activity while the test system is used for patient testing.
    Response: We accept these positive comments and are retaining the 
requirements for the establishment and verification of method 
performance specifications formerly at Sec.  493.1213 (now at Sec.  
493.1253). However, we realize the QC record retention requirements 
formerly at Sec.  493.1221 may have been misinterpreted as permitting 
the laboratory to discard method performance specification records 
after a 2-year period even though the method may have continued to be 
used beyond this timeframe. Therefore, the analytic systems record 
retention requirement formerly at Sec.  493.1221 (now at Sec.  
493.1105(a)(3)(i)) specifies that records of the laboratory's 
establishment and verification of method performance specifications 
must be retained for the period of time the test system is in use by 
the laboratory, but not less than 2 years. In addition, we are revising 
the original QC record retention requirement to accommodate the 
reorganization of the regulation and clarify its intent.
    Comment: A few commenters disagreed in general with the

[[Page 3656]]

requirements at Sec.  493.1215, Equipment maintenance and function 
checks. Other commenters requested clarification. One commenter felt 
that the requirements were too stringent, and another offered specific 
language for revision. One commenter felt CMS, not the manufacturer, 
should establish the frequency for performing function checks.
    Response: Equipment maintenance and function checks are necessary 
to ensure accurate and reliable test performance. We are relocating the 
requirement formerly at Sec.  493.1215 (now at Sec.  493.1254) and 
renaming it Maintenance and function checks. Laboratories using 
unmodified manufacturers' equipment, instruments, or test systems must 
perform maintenance and function checks as defined by the manufacturer 
with at least the frequency specified by the manufacturer. Laboratories 
must also document maintenance and function checks performed. We are 
adding language at Sec.  493.1254(a)(2) requiring that function checks 
be within the manufacturer's established limits before conducting 
patient testing. We are also retaining the present requirement (now at 
Sec.  493.1254(b)) for laboratories to establish protocols that ensure 
proper test system performance, accurate and reliable test results and 
test reporting for equipment, instruments, or test systems developed 
in-house, commercially available but modified by the laboratory, or 
when protocols for maintenance and function checks are not provided by 
the manufacturer. In addition, laboratories must document the 
maintenance and function checks performed.
    Under this final rule, we are not defining intervals for the 
performance of maintenance or function checks because the manufacturer 
is better able to define the appropriate procedures and intervals 
necessary to maintain and ensure proper equipment, instrument, and test 
system performance.
    Comment: Several commenters suggested that Sec.  493.1217, 
calibration and calibration verification, or substantially equivalent 
requirements, should also apply to FDA-approved or cleared, unmodified 
moderate complexity testing at Sec.  493.1202(c). In addition, we 
received comments requesting clarification of Sec.  493.1217. One 
commenter stated that CMS, not the manufacturer, should establish the 
frequency of calibration. A manufacturer commented that a loose 
interpretation of the calibration verification requirement to assay 
calibration materials in the same manner as patient samples is needed 
for certain blood gas analytes because buffers and gases used to 
calibrate the instruments are not like patient samples and cannot be 
assayed in the same manner as patient samples.
    Response: We agree with the commenters and are specifying in this 
final rule that effective, April 24, 2003, calibration and calibration 
verification requirements (now at Sec.  493.1255) will apply to all 
nonwaived testing.
    To respond to the commenters' concerns that the calibration and 
calibration verification requirements are unclear, we are making some 
minor revisions in language for clarification purposes and removing 
duplicate requirements. For example, the definitions of calibration and 
calibration verification and reportable range are being slightly 
modified (now at Sec.  493.2). We are also removing the requirement 
formerly at Sec.  493.1217(b)(2)(ii)(B)(1) for laboratories to perform 
calibration verification using calibration materials appropriate for 
the methodology and, if possible, traceable to a reference method or 
reference material of known value to allow laboratories flexibility in 
choosing materials for calibration verification.
    In addition, we are retaining the requirement for laboratories, at 
a minimum, to perform calibration and calibration verification 
procedures using the manufacturers' test system instructions and the 
criteria verified or established by the laboratory formerly at 
Sec. Sec.  493.1217(b)(1) and 493.1217(b)(2) (now at Sec. Sec.  
493.1255(a)(1), 493.1255(a)(2), 493.1255(b)(1) and 493.1255(b)(2)). We 
are also retaining the requirement that calibration must be performed 
whenever calibration verification procedures are unacceptable and 
calibration verification be performed using a minimum of 3 values to 
verify the laboratory's reportable range, at least once every 6 months 
or whenever an event occurs as specified formerly at Sec.  
493.1217(b)(2)(ii)(C) (now at Sec.  493.1255(b)(3)).
    In response to the comment that the frequency of calibration be 
mandated by CMS, we are retaining the requirement formerly at Sec.  
493.1217(b)(1) (now at Sec.  493.1255(a)) that requires laboratories to 
calibrate according to the manufacturer's instructions, if provided, 
and the laboratory's specifications. We believe that laboratories 
should perform calibration at the interval specified by the 
manufacturer to ensure proper instrument and test system performance. 
For calibration verification formerly at Sec.  493.1217(b)(2) (now at 
Sec.  493.1255(b)), laboratories are to follow the manufacturer's 
specifications and the laboratory's established protocols for 
calibration verification that must be performed at least once every 6 
months. We believe this is the maximum interval allowable for verifying 
accuracy and stability. In addition, we are emphasizing that these 
regulations set forth minimal requirements. In establishing or 
verifying performance specifications as required at Sec.  493.1253, the 
laboratory may find it necessary to calibrate or verify calibration 
more frequently or to use more calibration materials than required at 
Sec.  493.1255.
    In response to the comment concerning the inability of testing 
calibration materials (buffers and gases) in the same manner as patient 
specimens when verifying the calibration of blood gas assays, we are 
retaining the additional requirements for routine chemistry formerly at 
Sec.  493.1245 (now at Sec.  493.1267) that supersede the general 
calibration and calibration requirements at Sec.  493.1255. Section 
493.1267(a) specifically addresses calibration and calibration 
verification of blood gas analyses and states the laboratory must 
calibrate or verify calibration according to the manufacturer's 
specifications and with at least the frequency recommended by the 
manufacturer. As long as the laboratory follows the manufacturer's 
calibration and calibration verification instructions for the blood gas 
instrument, the CLIA requirements for calibration and calibration 
verification are met.
    Comment: We received many comments concerning various components of 
Sec.  493.1218, Control procedures. Some commenters misread the CLIA 
regulation, and others offered specific language for revision. Most 
commenters opposed testing two levels of control material each day of 
use. One commenter indicated that the CLIA requirements are burdensome 
and will increase the cost of testing. Some commenters expressed 
concern that the requirements are arbitrary and do not recognize unit 
use test systems. Another commenter asked if procedural controls may be 
used to satisfy the control requirements.
    Response: We appreciate the commenters' concerns about the 
frequency and costs of performing control testing. However, CLIA 
regulations will continue to describe the purpose of control 
procedures, that is, to assess the accuracy and precision of test 
performance. The control procedures must monitor the complete 
analytical process by detecting immediate errors (those that occur due 
to test system failure, adverse environmental conditions or operator 
performance problems) and monitor over time the accuracy and precision 
of test performance that can be influenced by

[[Page 3657]]

subtle changes in test system performance, environmental conditions, 
and variance in operator performance (for example, different operators 
and same operator variations in specimen handling and testing).
    In response to the comments concerning unit use test systems and 
the use of procedural controls, we are making allowances for the use of 
procedural controls in Appendix C of the State Operations Manual (CMS 
Pub. 7) when equivalent quality procedures can be demonstrated.
    In addition, we are providing a definition for test system (now at 
Sec.  493.2). A test system is the instructions and all of the 
instrumentation, equipment, reagents, and/or supplies needed to perform 
an assay or examination and generate test results.
    A control material must detect errors in the entire testing 
process. It must also monitor the quality of the results provided by 
the test system. It may be supplied by the test system manufacturer or 
another source. We are also relocating the requirement for control 
materials to be tested in the same manner as patient samples formerly 
at Sec.  493.1218(c) (now at Sec.  493.1256(d)(8)) and clarifying that 
this requirement applies to control materials and that over time 
control testing must be rotated among all operators who perform the 
testing (now at Sec.  493.1256(d)(7)).
    We are reducing the frequency of testing control materials from 
``each run'' to ``each day of testing.'' We are retaining the former 
requirements for qualitative procedures (test positive and negative 
control materials) and quantitative procedures (test two levels of 
control material). For test procedures producing graded or titered 
results, we are relocating the requirement to test a negative control 
and a control of graded or titered reactivity from Syphilis serology 
and General immunology formerly at Sec. Sec.  493.1239(b) and 
493.1241(a), respectively (now at Sec.  493.1256(d)(3)(iii)).
    As part of updating the requirements for new technology and test 
methodologies formerly at Sec.  493.1218(b)(3) (now Sec.  
493.1256(d)(5)), we are revising the wording of the control requirement 
for electrophoresis procedures.
    Comment: One commenter urged that we remove specific stipulations 
for frequencies of performing QC or calibrations and substitute 
reference to an agency or professional association guidelines. The 
commenter also recommended that we accept alternate approaches 
suggested by a manufacturer as documented in test system instructions 
approved by the FDA. Another commenter suggested that Sec.  493.1218(a) 
be revised to state, ``that the laboratory should run controls as 
specified by the manufacturer's instructions.'' Several commenters and 
one organization stated it is the laboratory director's responsibility 
to design the control system needed to achieve the desired quality.
    Response: We consider the requirements established in subpart K as 
the minimum control measures needed to ensure accurate and reliable 
test results. According to the requirements formerly at Sec.  493.1213 
(now at Sec.  493.1253), each laboratory must verify or establish a 
test system's method performance specifications and use this 
information in determining appropriate calibration and control 
protocols. This may include more frequent testing and greater numbers 
of materials than specifically provided under CLIA regulations. For 
example, the laboratory is required to perform calibration and control 
procedures in the manner necessary to ensure quality results. In cases 
where the manufacturer's instructions require more stringent testing of 
calibrators, control materials, or both, the laboratory is required to 
follow the manufacturer's instructions. Therefore, we are clarifying 
that laboratories must follow the manufacturer's instructions for 
control testing if they meet or exceed the requirements now at Sec.  
493.1256(d)(3).
    We agree with the comment concerning the laboratory director's 
responsibility to determine appropriate control procedures to monitor 
the complete analytical process. This requirement is specified in CLIA 
regulations under the director's responsibilities at Sec.  
493.1407(e)(5) for moderate complexity testing and Sec.  493.1445(e)(5) 
for high complexity testing.
    Comment: A commenter suggested that acceptable control materials 
are two samples of different concentrations of controls or two 
concentrations of calibration material of a different lot other than 
the lot used for assay calibration, or any combination that results in 
both normal and abnormal values.
    Response: We agree with the commenter and emphasize that any 
calibrator used as control material must be of a different lot number 
than the one(s) used to establish a cutoff value or calibrate the 
assay. Therefore, we are revising this requirement formerly at Sec.  
493.1218(b)(2)(now at Sec.  493.1256(d)(9)) to clarify that the 
calibrators used as control materials must be of different 
concentrations than the calibrators employed to set instrumentation. We 
recommend that the acceptable range of control materials reflect some 
clinical decision points, both normal and abnormal.
    Comment: One commenter suggested that Sec.  493.1218(d) be revised 
to include a provision that if the performance specifications at Sec.  
493.1213 are exceeded, the laboratory must take corrective action 
before patient testing can continue.
    Response: We agree with the commenter. The requirements formerly at 
Sec.  493.1219(a) (now at Sec.  493.1282(b)(1)) require corrective 
action, and the requirements formerly at Sec.  493.1701 (now at Sec.  
493.1289(b)) require the laboratory to review the effectiveness of its 
corrective actions and, if necessary, revise policies and procedures to 
prevent recurring problems.
    Comment: One commenter disagreed with the requirement to check each 
batch or shipment of media.
    Response: The CLIA regulations allow laboratories to use the 
manufacturer's QC checks of certain media, provided the manufacturer's 
product insert specifies that the manufacturer's QC checks meet the 
NCCLS standards for media QC formerly at Sec.  493.1218(f)(4), now 
addressed in Appendix C of the State Operations Manual (CMS Pub. 7). 
For media not included by NCCLS, we believe it is critical that the 
laboratory check each batch of media to ensure that it is not 
contaminated, supports growth of appropriate organisms, and elicits the 
correct biochemical response(s). The former Sec.  493.1218(f)(4) (now 
Sec.  493.1256(e)(4)) clarifies that media checks must be performed 
before, or concurrent with, initial use of media.
    Comment: A few commenters expressed disagreement with the 
requirement to evaluate the detection phase of direct antigen systems 
and the extraction phase when it is included.
    Response: We believe the laboratory must verify that all steps of a 
testing procedure are functioning properly to prevent erroneous 
results. Therefore, we are retaining the requirement formerly at Sec.  
493.1218(b)(4) (now at Sec.  493.1256(d)(3)(iv)) that requires 
laboratories to test two control materials, one that is capable of 
detecting errors in the extraction phase.
    Comment: One commenter agreed with requiring the determination of 
statistical parameters for each lot of calibration or control 
materials.
    Response: We are retaining the requirement formerly at Sec.  
493.1218(d)(2) (now at Sec.  493.1256(d)(10)(i)) for laboratories to 
have statistical

[[Page 3658]]

parameters for each lot of control material. In addition, we are 
clarifying that the requirement applies to controls with quantitative 
results. When calibration materials (not used to establish a cutoff 
value or calibrate the test system) are used as control materials, the 
laboratory must have statistical parameters for each lot of calibration 
material.
    Comment: Some comments received were in reference to Sec.  
493.1219, Remedial actions. One commenter requested clarification and 
another requested deletion of Sec.  493.1219(a)(2) that requires the 
laboratory to document all remedial action taken when patient test 
results are outside of the laboratory's reportable range for the test 
system. One individual asked for clarification of Sec.  493.1219(d)(3) 
that requires the laboratory to maintain exact duplicates of both 
original and corrected reports for 2 years when errors in the reported 
test results are detected. One commenter suggested that no patient 
results that are less than the lowest calibrator or higher than the 
highest calibrator can be reported unless they are reported as less 
than or greater than the lowest or highest calibrator or the patient 
specimen is diluted to determine a higher value.
    Response: The requirement formerly at Sec.  493.1219(a)(2) (now at 
Sec.  493.1282(b)(1)(ii)) requires documentation of all remedial 
actions (now ``corrective'' actions) when patient values are outside of 
the laboratory's reportable range of patient test results. The 
documentation can be an instrument printout or other document that 
reflects the problem, corrective action, and outcome. The laboratories 
must retain this information for the required period and the corrective 
actions themselves may be as elementary as diluting and retesting the 
specimen. We are not making any revisions to this requirement.
    The requirement formerly at Sec.  493.1219(d)(3) (now at Sec.  
493.1105(a)(6)) requires the laboratory to maintain a copy of the 
original report, or be able to retrieve a copy of the original report 
and the corrected report for 2 years. Copies of test reports may be 
manually written, photocopies, electronically generated, or maintained 
on microfilm provided they contain all of the information supplied on 
the original test record or report.
    We agree with the suggestion that results outside of the reportable 
range of the test system may not be reported without corrective action 
or explanatory remarks. Therefore, requirements formerly at Sec.  
493.1219 (now at Sec.  493.1282, Corrective actions) require 
laboratories to have corrective action policies and procedures that are 
followed as necessary to maintain the laboratory's operation for 
testing patient specimens in a manner that ensures accurate and 
reliable patient test results and reports. This includes policies 
governing the reporting of patient results that exceed the reportable 
range of the test system. The analytic assessment requirements at Sec.  
493.1289 require the laboratory to monitor and evaluate the corrective 
actions taken and revise policies and procedures as necessary to 
prevent recurrences of problems.
    Comment: One commenter suggested that CLIA rules require all 
original worksheets and instrument printouts to be retained for 6 
months, indicating that some laboratories destroy, delete, or erase 
records of unacceptable QC in order to avoid showing remedial action 
and reassessment of all patient tests results associated with the 
failure.
    Response: We understand the concerns expressed by the commenter. 
However, we believe the CLIA regulations adequately address documenting 
all control procedures performed formerly at Sec.  493.1221 (now at 
Sec. Sec.  493.1256(g) and 493.1105(a)(3)), maintaining records of all 
control procedures performed formerly at Sec.  493.1221 (now Sec.  
493.1105(a)(3)), assessing corrective actions taken formerly at Sec.  
493.1705 (now at Sec. Sec.  493.1289(a) and (b)) and retention of the 
original worksheets and instrument printouts for a period of 2 years or 
more formerly at Sec.  493.1107 (now at Sec.  493.1105(a)(3)). We also 
believe that if the laboratory deletes or alters a control result in 
any manner, it is expected that the laboratory will document the exact 
circumstances in which deletion or alteration occurred and document all 
corrective actions taken to prevent reoccurrence.
    Comment: One commenter felt that there should be a requirement that 
any abnormal, life-threatening, or panic value result obtained on a 
moderate complexity test should be repeated by a more accurate method 
of testing.
    Response: The requirement formerly at Sec.  493.1109(f) (now at 
Sec.  493.1251(b)(13)) requires laboratories to develop written 
procedures for reporting life-threatening results (panic or alert 
values). In addition, under the requirement formerly at Sec.  
493.1109(f) (now Sec.  493.1291(g)) laboratories must immediately alert 
the individual or entity that requested the test and, if applicable, 
the individual responsible for using the test results when any test 
result indicates an imminently life-threatening condition. In addition, 
it is the responsibility of each laboratory to ensure that the results 
it reports are accurate. Repeat testing is one method of verifying the 
test results. However, it is up to each laboratory to determine the 
protocols it will follow to confirm the test results that it reports.
Section 493.1223 Condition: Quality Control-Specialties and 
Subspecialtes for Tests of Moderate or High Complexity, or Both
    Specific comments received and response to comments regarding Sec.  
493.1223, specialty or subspecialty control requirements are set forth 
below.
    Comment: One commenter stated that the specialty and subspecialty 
QC requirements are too lenient.
    Response: The specialty and subspecialty QC requirements are 
minimum requirements that reflect good laboratory practice and must be 
followed by all laboratories performing nonwaived testing. However, 
based on the laboratory's establishment and verification of its test 
systems' performance specifications (now at Sec.  493.1253), the 
laboratory may determine that, to ensure accurate and reliable test 
results, it must implement more stringent control procedures than the 
minimum requirements imposed. In addition, it is the laboratory 
director's responsibilities to ensure that the laboratory has systems 
that ensure the quality of the laboratory services provided and 
identify failures in quality as they occur (Sec. Sec.  493.1407(e)(5) 
and 493.1445(e)(5)).
    Comment: One commenter disagreed with Sec.  493.1223 stating a 
laboratory could lose approval to perform testing in an entire 
specialty or subspecialty if it is deficient in performing QC for a 
single test. The commenter urged that the language be changed to 
``Failure to satisfy requirements for an individual test or analyte 
would result in loss of approval for that test or analyte only.''
    Response: We emphasize that CLIA certification of laboratories is 
not granted on a test-by-test basis, but by specialty or subspecialty 
of testing. Therefore, if a laboratory has significant problems related 
to only one test or analyte in a specialty or subspecialty and the 
laboratory fails to correct those problems, it could jeopardize its 
certification for the specialty or subspecialty area. For example, the 
laboratory is notified in writing of the deficiencies found during a 
survey and is given an opportunity to correct the deficiencies. If the 
laboratory does not correct the deficiencies, sanctions could be 
imposed as specified in Subpart R--Enforcement Procedures. Therefore, 
we are deleting the enforcement

[[Page 3659]]

information formerly at Sec.  493.1223 because subpart R contains this 
information. In addition, revocation of specialty or subspecialty 
certification for problems related to a particular test would be taken 
only as a last resort.
Sections 493.1225 Condition: Microbiology; 493.1227 Condition: 
Bacteriology; 493.1229 Condition: Mycobacteriology; 493.1231 Condition: 
Mycology; 493.1233 Condition: Parasitology; and 493.1235 Condition: 
Virology
    Specific comments received and response to comments regarding 
Sec. Sec.  493.1225, 493.1227, 493.1229, 493.1231, 493.1233, and 
493.1235 are set forth below.
    Comment: A professional organization, the American Society for 
Microbiology (ASM), commented that the CLIA QC requirements should be 
revised over time as new information is made available about the 
performance parameters of reagents or test systems. At a CLIAC meeting, 
this organization presented data on control failures for commercial 
microbiology reagents and stains and suggested that the current 
frequencies for control testing of a number of microbiology tests or 
reagents are excessive. ASM collected the data via two surveys of 304 
clinical microbiology laboratories that perform varying levels of 
microbiological testing. It included failure rates for a total of 
14,731 lots of reagents and stains, representing 21 different tests. 
Reagents and stains for 11 of the tests surveyed currently have control 
testing frequencies specified in the CLIA regulations: catalase, 
oxidase, coagulase plasma, Salmonella antisera, Shigella antisera, Gram 
stain reagents, optochin, bacitracin, Cefinase\Tm\ (beta lactamase), X 
and V factor strips and disks, and germ tube test. In this final rule, 
specific control testing frequencies are not given for eight reagents 
(spot indole, staphylococcal latex reagents, streptococcal latex 
grouping reagents, PYR disks, deoxycholate, KOH (fungal), LAP disks, 
and ALA) and two stains (lactophenol cotton blue and methylene blue). 
Based on the results of their surveys, the ASM proposed that 
laboratories should only be required to test new lot numbers of those 
commercial microbiology reagents that had a 98 percent or greater 
success rate (all reagents they surveyed met this requirement). In 
addition to testing each new lot, ASM recommended that laboratories 
test Salmonella and Shigella antisera every 6 months thereafter. ASM 
recommended that for epidemiological testing conducted in public health 
laboratories, the frequency for testing Salmonella and Shigella 
antisera should be determined by the periodicity supported by each 
laboratory's data.
    In making this presentation, ASM stated that the changes they were 
proposing would improve the cost effectiveness of the CLIA program and 
quality assurance programs in clinical laboratories without 
compromising public health. The CLIAC supported the proposal and 
recommended the incorporation of these changes into the CLIA 
regulations.
    Response: We appreciate the efforts of ASM, and the data they 
provided. The survey results provided the supporting information and 
data needed to revise the control testing frequency requirements. Based 
on the low failure rates for the commercial microbiology reagents 
surveyed, we agree it is adequate to test the majority of these 
reagents with each batch (prepared in-house), lot number (commercially 
prepared), and shipment when prepared or opened for positive, negative, 
and graded reactivity, as applicable. We also agree with checking 
antisera initially and once every 6 months thereafter except for 
epidemiological testing that is not subject to CLIA.
    For two of the stains surveyed, the Gram stain and methylene blue, 
we do not agree that the low failure rate of the reagents is sufficient 
reason to decrease the stringency of the control requirements. The Gram 
stain procedure uses several reagents and has multiple steps that 
require specific timing for accurate results. Also, interpretation of 
the stained smear requires individual skill and expertise. By 
decreasing the frequency of control testing for this procedure to once 
every batch, lot number, and shipment, small laboratories that perform 
only rare Gram stains on direct specimens may not test controls for a 
period of months. We do not believe this is appropriate for a critical 
test used, in some cases, to presumptively diagnose an infectious 
disease (for example, direct smear for Neisseria gonorrhoeae). For this 
reason, we are maintaining the current weekly control testing 
requirement for Gram stain in addition to testing with each new batch, 
lot number and shipment.
    Similar to the Gram stain usage in small laboratories, methylene 
blue stains may not be performed for an extended period of time, 
especially in laboratories that do not routinely use this staining 
procedure. We do not believe it is overly burdensome to require control 
testing of this stain each day of use.
    In making the revisions discussed above, we deleted the specific 
control requirements for the reagents surveyed by ASM in the 
subspecialties of bacteriology formerly at Sec.  493.1227 (now at Sec.  
493.1261) and mycology formerly at Sec.  493.1231 (now at Sec.  
493.1263), except for requiring in bacteriology that the Gram stain be 
tested each week of use, and antisera be tested when each batch, lot 
number, and shipment is prepared or opened, and once every 6 months 
thereafter. We are also requiring in mycology that the laboratory check 
each batch, lot number, and shipment of lactophenol cotton blue when 
prepared or opened for intended reactivity with control organisms. 
Additional control testing for lactophenol cotton blue is not required. 
The required control testing frequencies for other reagents and stains 
will default to the general control procedures requirements formerly at 
Sec.  493.1218(f) (now at Sec.  493.1256(e)(1) and (2)). The general 
control requirements for reagents include testing each batch (prepared 
in-house), lot number (commercially prepared) and shipment when 
prepared or opened. The general control requirements for stains (for 
example, methylene blue) include testing staining materials for 
intended reactivity each day of use. As indicated by ASM, we believe 
these changes will decrease the cost of microbiology testing, without 
significantly affecting the quality of the test results.
    The CLIAC requested further input from ASM on appropriate control 
requirements for microbiology. ASM submitted the following 
recommendations based on consultation with clinical microbiologists:
    [sbull] The mycology requirement (for auxanographic media for 
nitrate assimilation) to check the nitrate reagent each day of use with 
a peptone control is not relevant since most laboratories no longer 
perform this test for fungal identification. This requirement could be 
deleted, and if laboratories do use the procedure, it would be 
sufficient to perform control testing with each batch or lot.
    [sbull] The requirement for parasitology laboratories to check 
permanent stains, each month of use, with a fecal sample should be 
changed to ``with a fecal sample or commercial QC slide.''
    [sbull] To control the decontamination process for mycobacteriology 
culture specimens, process a specimen containing Mycobacterium 
fortuitum with each new lot number or batch of decontaminating agent.
    [sbull] The frequency of control testing should be standardized for 
all microbiology subspecialties. Although there has been no data 
collected for reagents or stains used in subspecialties

[[Page 3660]]

other than bacteriology, ASM suggested that it was their experience 
that these reagents and stains perform as well as the reagents surveyed 
for bacteriology.
    [sbull] Molecular amplification control procedures should adhere to 
standards outlined in the NCCLS document ``Molecular Diagnostic Methods 
for Infectious Diseases, MM3-A, 1995.'' At a minimum, control 
procedures for these tests should validate cell lysis, absence of 
inhibitors, absence of contamination, and adequate amplification. The 
following controls should be included with each run:
    [sbull] Positive control (low range of assay sensitivity).
    [sbull] One to five negative controls.
    [sbull] Internal control.
    [sbull] Quantitative assays should include two to three standards 
of known copy number. For microbial genotyping, control procedures 
should include at least two isolates of the same species being tested. 
One isolate should have the same phenotype as the unknown, and one 
should be a different phenotype.
    Response: Our responses to the above recommendations are set forth 
below.
    We agree that the mycology requirement for control testing of 
nitrate assimilation on auxanographic media is not relevant for the 
large majority of laboratories performing fungal identification, and 
have deleted that requirement. If laboratories use the procedure, they 
will be required, as stated formerly at Sec.  493.1218(f) (now at Sec.  
493.1256(e)(1)) to test the medium and reagents with each batch 
(prepared in-house), lot number (commercially prepared), and shipment 
when prepared or opened. This will be the same control testing as 
required for other reagents and media used for fungal identification 
procedures.
    The language formerly at Sec.  493.1233(c) (now at Sec.  
493.1264(c)) requires laboratories to check permanent stains each month 
of use by using a fecal sample control. This terminology does not 
preclude the use of a fecal sample as a control or a commercially 
prepared control slide. The requirement remains as written in existing 
CLIA regulations; however, we will note this clarification in Appendix 
C of the State Operations Manual (CMS Pub. 7).
    We recognize ASM's concern that the mycobacteriology 
decontamination process be monitored and adequately controlled to 
ensure that the decontaminating agent is of the proper strength to kill 
contaminating organisms without destroying mycobacteria (especially 
Mycobacterium tuberculosis). However, the method they suggested for 
doing this is only one way in which it may be accomplished. There are a 
number of other ways in which this process may be controlled (for 
example, monitoring the contamination rate over time to ensure the 
appropriate organisms are being killed). In an effort to maintain 
flexibility in CLIA regulations, in this final rule, we are not adding 
this ASM proposed control requirement to those for mycobacteriology. As 
noted formerly at Sec.  493.1103(a) (now at Sec.  493.1232), the 
laboratory must establish and follow written policies and procedures 
that assure optimum integrity of patient specimens from the time they 
are collected until testing has been completed and results reported. In 
addition, former Sec.  493.1103(a) (now at Sec.  493.1242(a)(6)) 
requires laboratories to have and follow written policies and 
procedures for specimen processing, and former Sec.  493.1703 (now at 
Sec. Sec.  493.1249(a) and (b)) requires the monitoring and assessment 
of these policies and procedures, and the implementation of corrective 
actions to resolve problems that are identified. These requirements 
ensure that the processing of mycobacterial specimens is monitored, 
assessed, and controlled, while allowing the laboratory to use any of 
several acceptable methods to do so.
    We agree with ASM that, whenever possible, the frequency for 
control testing should be standardized for all microbiology 
subspecialties. Frequencies for individual reagents and stains are not 
specified in CLIA regulation for mycology and virology. For 
parasitology, a frequency requirement (to test once a month) is only 
given for permanent stains. The frequency requirement for all other 
reagents and stains in these subspecialties is the default contained in 
the general control procedure requirements that are now at Sec.  
493.1256(e)(1) and (2).
    We agree appropriate requirements for molecular amplification 
procedures are needed, and that the NCCLS standards are an excellent 
reference for laboratories to use. Requirements addressing most of the 
recommendations made by ASM for amplification procedures are included 
in CLIA regulations, although not as specifically as suggested by this 
organization. CLIA regulations require the laboratory director to have 
control procedures to monitor the complete analytic process. For 
amplification procedures this includes, in general, validating cell 
lysis and ensuring absence of inhibitors, absence of contamination, and 
adequate amplification. The CLIA requirements for control procedures 
for all tests are now at Sec.  493.1256(d). This provision requires all 
laboratories to follow manufacturer's instructions for control testing, 
and to, at minimum, conduct a test that includes two control materials 
of different concentrations (a positive and negative control are 
required for qualitative tests) on each day patient specimens are 
tested. CLIA regulations require that if the laboratory determines 
additional numbers or types of controls, or a greater frequency of 
running controls is needed to detect immediate error and monitor test 
performance over time, the numbers, types, and or frequency of controls 
must be increased accordingly.
    While we agree with the recommendation made by ASM describing the 
positive and negative controls that should be used for molecular 
amplification procedures, the CLIA control requirements are minimum 
requirements and do not specify that a positive control must be at the 
low range of assay sensitivity, or that more than one negative control 
be tested daily. Likewise, these minimum requirements do not specify 
the types of controls that must be included with microbial genotyping, 
but only that two controls must be tested each day patient specimens 
are tested.
    However, if test system instructions specify such control testing, 
or if the laboratory determines (during its initial evaluation of the 
test system at Sec.  493.1253) that more controls are needed, the 
additional control testing must be performed.
    For molecular amplification procedures, ASM also recommended the 
inclusion of an internal control in each run, primarily to detect 
inhibition of the amplification process. We agree that for some 
amplification procedures the presence of inhibitors or interfering 
substances in certain specimens may cause false negative test results, 
and that for these procedures, a control system is necessary to detect 
inhibition. However, as noted by NCCLS, inhibitors are not a 
significant source of false negative results for every test, and if 
inhibitors or interfering substances are encountered only rarely, NCCLS 
does not recommend running controls for inhibition. Therefore, we have 
added a requirement at Sec.  493.1256(d)(3)(v) that states, if reaction 
inhibition is a significant source of false negative results, the 
laboratory must include a control system to detect such inhibition.
    In response to the ASM recommendation that quantitative assays 
include two to three standards of known copy number, as stated above, 
under CLIA regulations, quantitative

[[Page 3661]]

tests must include at least two control materials of different 
concentrations per day. Standards may be used in lieu of control 
materials, as long as they are not the same as the materials used to 
calibrate the test system or establish a cutoff.
    In reviewing the CLIA regulations concerning control procedures and 
QA requirements for molecular amplification procedures, the CLIAC 
discussed appropriate control procedures and QA for genetic testing 
(September 16, 1998 through September 17, 1998). CLIAC recommended that 
controls for genetic testing should be considered for laboratories in 
general, including ensuring that adequate controls are in place to 
minimize contamination. This is especially important when performing 
molecular amplification procedures. To ensure the control of 
contamination, we have amended the requirements for facilities, 
formerly at Sec.  493.1204(a) (now at Sec.  493.1101(a)) to require 
laboratories to be constructed, arranged, and maintained to minimize 
contamination of patient specimens, equipment, instruments, reagents, 
materials, and supplies. A uni-directional workflow must be maintained 
for molecular amplification procedures not contained in closed systems. 
This must include physically separate areas for specimen preparation, 
amplification and product detection and, as applicable, reagent 
preparation. We believe these measures will decrease the potential for 
contamination to the extent possible in a clinical laboratory.
    Comment: Several commenters requested clarification of the control 
requirements for kit systems used for bacterial and fungal 
identification. One commenter specifically requested the addition of a 
provision at Sec.  493.1231, Mycology, that would require the testing 
of each new shipment of test kits or strips used for organism 
identification with organisms giving positive and negative reactions 
for each test before or concurrent with testing of clinical isolates. 
Another commenter questioned whether these systems would be subject to 
the requirement described at Sec.  493.1202(c)(4) to test at least two 
levels of control materials each day of testing.
    Response: We agree with the commenter that in mycology, or any 
other subspecialty area of microbiology, new shipments of test kits or 
strips used for organism identification should be tested with organisms 
giving positive and negative reactions for each test before or 
concurrent with initial testing of clinical isolates. This includes 
identification kits or panels that are inoculated and read manually, 
and those that are part of an automated instrument system. We are 
retaining the requirement formerly at Sec.  493.1218(f)(1) (now at 
Sec.  493.1256(e)(1)) that laboratories check each batch (prepared in-
house), lot number (commercially prepared), shipment of reagents, 
disks, stains, antisera, and identification systems (systems using two 
or more substrates and/or reagents) when prepared or opened for 
positive and negative reactivity. We do not believe additional testing 
of these systems is needed if they are stored and maintained under 
appropriate conditions. Further testing is only necessary if labile 
reagents must be prepared or used each time the kit is used or if 
specified by the manufacturer.
    Comment: Several commenters requested clarification of the control 
requirement at Sec.  493.1218(b)(1) for qualitative tests as applied to 
microbiology procedures. The commenters asked which of the biochemical 
tests or media used for microbial identification would be considered 
qualitative tests.
    Response: Biochemical tests using specific reagents or growth tests 
that employ selective or differential media (for example, indole tests, 
citrate media) that are a part of the total system of identification 
from culture are not considered qualitative tests in microbiology. 
Therefore, we are retaining the requirement formerly at Sec.  
493.1218(f)(1) (now at Sec.  493.1256(e)(1)) that states laboratories 
must check each new batch (prepared in-house), lot number (commercially 
prepared), and shipment when prepared or opened for positive, negative, 
and graded reactivity, if applicable. Specifically, former Sec.  
493.1218(f)(4) (now at Sec.  493.1256(e)(1) and (4)) requires each 
batch of media to be checked before or concurrent with initial use for 
sterility, and its ability to support, select, or inhibit growth, as 
intended, and/or provide the appropriate biochemical response. The 
manufacturer's control checks of media may be used if the product 
insert specifies they meet the NCCLS standards for media control 
testing. These individual procedures do not require control checks with 
each run of patient specimens or further testing unless specified by 
the manufacturer or under specialty or subspecialty control 
requirements. Biochemical tests or media that provide microbial 
identification from a direct specimen or culture (for example, direct 
antigen tests for group A streptococcus, bacterial serotyping from 
culture) are considered qualitative microbiology tests and are graded 
for reactivity. We are retaining the control procedures requirements 
for qualitative test systems formerly at Sec.  493.1218(b)(1) (now at 
Sec.  493.1256(d)(3)(ii)).
    Comment: One commenter recommended we add ``XV discs or strips'' to 
Sec.  493.1227(a)(2) that requires testing both positive and negative 
control organisms each week of use, and delete Sec.  493.1227(b) that 
requires testing the XV discs or strips with only a positive control 
organism each week of use.
    Response: Testing of XV discs or strips was limited to only a 
positive control each week of use because there is no known available 
control to check negative reactivity for the group of organisms that 
this test identifies. We are deleting the specific QC requirements for 
testing X, V, and XV disks or strips. These disks or strips are now 
subject to the general control procedure requirements formerly at Sec.  
493.1218(f)(1) (now at Sec.  493.1256(e)(1)) that include testing each 
new batch (prepared in-house), lot number (commercially prepared), and 
shipment when prepared or opened for positive and negative reactivity. 
Since there is no control available to check negative reactivity for XV 
disks or strips, the use of only a positive control for XV disks or 
strips will be deemed to meet the CLIA regulation as specified in 
Appendix C of the State Operations Manual (CMS Pub. 7).
    Comment: Several commenters recommended we change the control 
requirement for daily testing of antimicrobial susceptibility 
procedures to a weekly requirement, as specified by NCCLS. One 
commenter also suggested manufacturers develop control procedures 
consistent with NCCLS antimicrobial susceptibility testing standards 
whenever feasible.
    Response: CLIA requires daily control checks for antimicrobial 
susceptibility testing, formerly at Sec.  493.1227(c)(2) (now at Sec.  
493.1261(b)(1)) unless CMS approves a procedure that provides 
equivalent quality testing as specified in Appendix C of the State 
Operations Manual (CMS Pub. 7). In this case, the procedure providing 
equivalent quality testing is the NCCLS standard allowing the 
laboratory to perform weekly control testing of antimicrobial 
susceptibility procedures after establishing accuracy control limits 
through initial daily testing. The laboratory may continue performing 
weekly control testing provided the control results do not exceed the 
established limits.
    Comment: One commenter requested clarification of the control 
requirements for antimicrobial susceptibility testing

[[Page 3662]]

with regard to the frequency of testing the disks, media, and overall 
procedure. The commenter felt that there is a contradiction between 
Sec. Sec.  493.1227(c) and (c)(2) and that one of these statements 
should be deleted.
    Response: In the former regulation, antimicrobial susceptibility 
testing requires that whenever a new batch of media or a new lot number 
and shipment of antimicrobial agents (disks) are put into use, the 
laboratory must verify that the media and agents perform within 
acceptable control parameters for testing. Following this initial 
verification that the test components (that is, media and antimicrobial 
agents) are working appropriately, the test procedure must be checked 
routinely with appropriate control strains to ensure that it is being 
performed accurately and all components of the procedure continue to 
work properly. This routine control procedure must be performed each 
day of patient testing or can be performed weekly. The weekly QC 
testing will be deemed to meet CLIA requirements, if performed as 
specified in the approved procedure providing equivalent quality 
testing in Appendix C of the State Operations Manual (CMS Pub. 7). The 
control organisms must be within established control limits before 
patient results can be reported.
    Although we did not intend for the requirements at Sec. Sec.  
493.1227(c) and (c)(2) to appear contradictory, we are revising the 
language now at Sec.  493.1261(b) for clarification of these 
requirements. In addition, we are making conforming changes to the 
language pertaining to the requirements for antimycobacterial and 
antifungal susceptibility testing for consistency and to be current 
with testing performed in these subspecialties. These requirements, 
formerly at Sec. Sec.  493.1229(d) and 493.1231(d), are now at 
Sec. Sec.  493.1262(b) and 493.1263(b).
    Comment: A number of commenters stated the control requirements for 
identification procedures used in mycobacteriology at Sec.  493.1229(a) 
should not selectively require positive and negative acid-fast control 
organisms to check the iron-uptake test each day of use while requiring 
only a positive acid-fast control for all other procedures. The 
commenters recommended that all identification procedures used in 
mycobacteriology be tested each day of use with an acid-fast organism 
that produces a positive result, and an acid-fast organism that 
produces a negative result.
    Response: We agree with these commenters and because the incidence 
of infection caused by a variety of mycobacteria is increasing 
significantly, it is important for laboratories to accurately identify 
individual species within this genus. This results in increasing 
numbers and types of identification procedures being performed and it 
is critical that the accuracy of each of these tests be verified each 
day of use. This can best be ensured each day of use by including both 
an acid-fast control organism that produces a positive reaction and an 
acid-fast control organism that produces a negative reaction for each 
test. We are revising the requirement formerly at Sec.  493.1229(a) 
(now at Sec.  493.1262(a)) to reflect this change.
    Comment: One commenter expressed concerns regarding the expense of 
testing controls and stated that the frequency for checking positive 
and negative reactivity of the BACTEC NAP test used to identify M. 
tuberculosis should be changed from each day of use to each week of 
use. This commenter suggested the requirement for testing a positive 
control each day of use could be satisfied by subculturing the growth 
from the BACTEC bottle to a solid media to detect appropriate colony 
and microscopic morphology.
    Response: The control requirements were written to address test 
complexity and specialties or subspecialties of testing, not specific 
test systems or procedures. Test-specific CLIA regulations are only 
developed when tests are not adequately addressed in the general or 
specialty or subspecialty requirements. The commenter requested a 
change in CLIA regulation because of the expense of performing controls 
each time the BACTEC NAP test is set up. The alternative method that 
the commenter suggests for a positive control is not actually a control 
on the ability of the NAP test to inhibit growth of M. tuberculosis, 
but is a confirmatory test for the presence of this organism.
    Although we agree with confirming results of the NAP test, it is 
not the same as using positive and negative control organisms to check 
the NAP vials for their ability to inhibit growth of M. tuberculosis 
and to allow growth of other mycobacteria. However, we understand the 
financial concerns associated with running positive and negative 
controls each day of use for this test. Since the test has a growth 
control included as part of each test, and the manufacturer indicates 
the media is stable and does not recommend testing positive and 
negative organisms as frequently as each day of use, we agree with the 
commenter that laboratories should only be required to check positive 
and negative control organisms each week of use. In addition, we are 
specifying this requirement as provided at Sec.  493.1256 as an 
alternative procedure in Appendix C of the State Operations Manual (CMS 
Pub. 7).
    Comment: One commenter stated positive and negative reactivity 
should be checked each day of use for all acid-fast staining 
procedures, rather than each week of use.
    Response: We agree with the commenter that both fluorochrome and 
conventional acid-fast stains should be tested more frequently than 
each week of use and that both positive and negative control organisms 
should be tested. Nonpathogenic mycobacteria in water supplies have 
been found to contaminate buffers, rinse water, or other reagents, 
producing false positive staining results. Given the widespread use of 
acid-fast stains with the increasing incidence of mycobacterial 
disease, it is critical that the accuracy of these tests be verified 
each day of use. Therefore, we are deleting the requirements formerly 
at Sec. Sec.  493.1229(b) through 493.1229(c) for testing fluorochrome 
and conventional acid-fast stains each week of use. The requirement for 
testing conventional acid-fast stains will now default to the general 
control requirement for stains formerly at Sec.  493.1218(f)(2) (now at 
Sec.  493.1256(e)(2)) that requires testing staining materials for 
intended reactivity each day of use. For stains that provide positive 
and negative reactivity (intended reactivity), we are revising the 
language to clarify that stains must be tested with positive and 
negative controls each day of use. By eliminating the subspecialty 
requirement for fluorochrome acid-fast stains, the general control 
requirement for fluorescent stains formerly at Sec.  493.1218(f)(3) 
(now at Sec.  493.1256(e)(3)) becomes applicable to these procedures. 
This general requirement specifies testing for positive and negative 
reactivity each time of use. It is appropriate to require the same 
control testing for fluorochrome acid-fast stains as are required for 
all other fluorescent stains.
    Comment: One commenter recommended the deletion in bacteriology of 
testing positive and negative organisms each week of use for acid-fast 
stains as required in Sec.  493.1227(a)(2) and replacement of the 
mycology term ``acid-fast stain'' at Sec.  493.1231(c), with ``modified 
acid-fast stain.'' This commenter emphasized that acid-fast stains are 
used in mycobacteriology rather than bacteriology, and that the 
procedure for staining used in mycology is a modification of the acid-
fast stains performed in mycobacteriology.

[[Page 3663]]

    Response: We agree with this commenter on both of these points. 
Although acid-fast stains are occasionally performed in bacteriology, 
by deleting the requirement in bacteriology for testing acid-fast 
stains each week of use, it defaults to the general requirement 
formerly at Sec.  493.1218(f)(2) (now at Sec.  493.1256(e)(2)) that 
requires laboratories to test staining materials for their intended 
reactivity (including positive and negative reactivity, as appropriate) 
each day of use. We agree with the commenter that the staining 
procedure in mycology is a modification of acid-fast stain used in 
mycobacteriology; therefore, we are deleting the requirement formerly 
at Sec.  493.1231(c) for performing control testing each week of use 
for (modified) acid-fast stains. Again, this results in the control 
requirement for these stains defaulting to the general requirement for 
testing each day of use and is reasonable based on the fact that we are 
now requiring positive and negative controls for all acid-fast stains 
each day of use.
    Comment: One commenter stated that the control regulation for 
mycology and mycobacteriology should require the use of a safety 
cabinet when testing in these specialty areas.
    Response: We agree with the commenter that safety is an important 
factor in laboratory testing, formerly at Sec.  493.1204(b) (now at 
Sec.  493.1101(d)) and laboratories are required to maintain a safe 
testing environment. Safety precautions must be established and 
observed to ensure protection from biohazardous materials. Under 
Sec. Sec.  493.1445(e)(2) and 493.1407(e)(2), the laboratory director 
is responsible for ensuring a safe environment is provided for 
employees conducting non-waived testing. In addition, other government 
agencies enforce State and local laws and other Federal standards that 
ensure protection of employees and the public from biohazardous 
materials. These agencies include the Occupational Safety and Health 
Administration and the Environmental Protection Agency.
    Comment: One commenter stated that the wording at Sec.  493.1235(c) 
is inappropriate. The commenter recommended the replacement of the word 
``culture'' (referring to uninoculated controls) with ``incubate'' or 
``hold.'' This individual stated that the use of the term culture as 
specified at Sec.  493.1235(c) generally means to inoculate and inspect 
for growth.
    Response: We agree with this commenter and are replacing the term 
``culture'' with the term ``incubate'' formerly at Sec.  493.1235(c) 
(now at Sec.  493.1265).
    Comment: A commenter requested clarification of the control 
requirements for virology as they pertain to direct antigen detection. 
This commenter recommended the addition of a statement to Sec.  
493.1235 following paragraph (c) that would read ``The above QC 
requirements are not applicable to virology testing performed using 
direct antigen detection methods.''
    Response: We agree with the commenter that the wording formerly at 
Sec.  493.1235(c) needs clarification. There are several types of tests 
that identify viruses, but this requirement only applies to cell 
culture methodologies used to isolate and identify viruses. Therefore, 
we are changing the language for this requirement, now at Sec.  
493.1265(a), to make it specific to cell culture methodologies.
Sections 493.1237 Condition: Diagnostic Immunology; 493.1239 Condition: 
Syphilis Serology; and 493.1241 Condition: General Immunology
    Specific comments received and response to comments regarding 
Sec. Sec.  493.1237, 493.1239, and 493.1241 are set forth below.
    Comment: A commenter stated Sec.  493.1239(e) and Sec.  
493.1241(d), which refer to facilities manufacturing blood and blood 
products, should be deleted. This individual believes CLIA regulations 
should not cover manufacturing requirements.
    Response: We disagree with the commenter. These requirements refer 
to testing requirements under CLIA regulations (donor specimens) 
regardless of where the testing is performed. However, we are moving 
these requirements, formerly under the subspecialties of syphilis 
serology and general immunology, and placing them with other 
requirements addressing the immunohematological collection, processing, 
dating, labeling, testing, and distribution of blood and blood products 
now at Sec.  493.1271, Immunohematology (formerly at Sec.  
493.1273(a)).
    Comment: One commenter requested clarification of the QC 
requirements for serological testing (both syphilis serology and 
general immunology) to run patient specimens concurrently with a 
positive serum control of known titer or controls of graded reactivity, 
if applicable, and a negative control. Specifically, this commenter 
questioned if these requirements refer to the additional controls run 
on a new kit to verify reproducibility, or if they pertain to the daily 
testing of the positive controls supplied in commercial kits. Other 
commenters objected to including two control materials each time 
patient testing is performed. One commenter thought only a positive 
control was necessary for immunology tests if the patient results were 
negative.
    Response: We agree with the commenters who objected to the syphilis 
serology and routine immunology requirements requiring two control 
materials each time patient testing is performed. With the development 
of more accurate and stable test systems, the requirements formerly at 
Sec.  493.1239(b) and Sec.  493.1241(a) for assaying controls 
concurrently with patient specimens are excessive for many of the test 
systems. We are, therefore, deleting these requirements. Laboratories 
performing these tests will now need to meet the applicable control 
procedures at Sec.  493.1256. In addition, the laboratory must meet the 
requirements that pertain to establishing or verifying a test system's 
performance specifications before putting a new test system into 
routine use formerly at Sec.  493.1213 (now at Sec.  493.1253).
    We disagree with the comment that testing only a positive control 
is sufficient if the patient results are negative. Laboratories, at a 
minimum, must follow the manufacturer's instructions and for 
qualitative tests, assay a positive and negative control each day of 
patient testing (now at Sec.  493.1256(d)(3)(ii)). For procedures 
producing graded or titered results, a control material with graded or 
titered reactivity, as applicable, and a negative control material must 
be assayed each day testing is performed formerly at Sec. Sec.  
493.1239(b) and 493.1241(a) (now at Sec.  493.1256(d)(3)(iii)). The 
control material supplied in commercial kits (test systems) may be used 
to meet the requirements formerly at Sec. Sec.  493.1239(b) and 
493.1241(a) (now at Sec.  493.1256(d)(3)(iii)) providing the material 
is of known reactivity (titered or graded, as applicable) and is not 
the same material used to establish a cutoff or calibrate the test 
system if calibration of the test system is required (now at 
493.1256(d)(9)).
Section 493.1245 Condition: Routine Chemistry
    Specific comments received and response to comments regarding Sec.  
493.1245 are set forth below.
    Comment: One commenter expressed concern that Sec. Sec.  
493.1245(c) and (d) could be interpreted to mean that the same material 
could be used to calibrate the instrument and verify or control the 
test run for blood gas analyzers. The commenter stated that this would 
not

[[Page 3664]]

detect problems arising from deteriorated or contaminated calibrating 
solutions. The commenter also recommended the reference to calibrators 
be deleted from these sections and that control testing be performed 
using only control material.
    Response: We agree with this commenter. It was never our intent to 
infer by the wording of these requirements that calibration material 
used to calibrate a test system could be used as a control to monitor 
the test system's performance. However, we allow the use of calibration 
material as a control material provided it is from a different lot 
number than that used to calibrate the test system or establish a cut-
off. Therefore, we are clarifying the use of calibration materials as 
control materials (now at Sec.  493.1256(d)(9)), and eliminating the 
terms ``calibration'' and ``calibration material'' from the blood gas 
analysis requirements (now at Sec.  493.1267).
    Comment: One commenter stated testing one sample of blood gas 
control per 8 hours of patient testing is not sufficient and is 
inconsistent with the general requirement for quantitative tests at 
Sec.  493.1218(b)(2) that requires two controls of different 
concentrations with each run of patient specimens. This commenter 
recommended that at least two levels of control be required every 8 
hour shift.
    Response: We revised the general control requirement formerly at 
Sec.  493.1218(b) (now at Sec.  493.1256(d)). The requirement now 
specifies, at a minimum, assaying two levels of control materials each 
day patient specimens are tested. We are deleting the term ``run'' from 
the regulation. Also, laboratories must perform control testing using 
the number and frequency specified by the manufacturer or established 
by the laboratory when those frequencies meet or exceed the minimum 
requirement. Therefore, the minimum control requirement for 
quantitative tests, unless a more frequent interval is recommended by 
the test system's manufacturer or the laboratory, is two control 
materials of different concentrations each day patient specimens are 
tested.
    The requirement for one control material per 8 hours for blood gas 
analyses, formerly at Sec.  493.1245 (now at Sec.  493.1267) exceeds 
these general QC requirements. The blood gas control requirements also 
require the laboratory to use a combination of control materials that 
check low and high values each day of testing. In addition, for blood 
gas instruments that do not internally verify calibration at least 
every 30 minutes, the laboratory must include one sample of control 
material each time patient samples are tested. This final rule provides 
minimum requirements. Based on the laboratory's verification of the 
test system's performance specifications before routine patient use 
(now at Sec.  493.1253) and establishment of its control procedures 
(now at Sec.  493.1256(d)), the laboratory may determine that it needs 
to run additional control materials or run control materials at a more 
frequent interval to assure accurate and reliable test results.
Section 493.1249 Condition: Toxicology
    Specific comments received and response to comments regarding Sec.  
493.1249 are set forth below.
    Comment: One commenter asked that the term ``drug abuse screening 
using thin layer chromatography'' at Sec.  493.1249, Toxicology be 
modified to read ``drugs-of-abuse screening using thin layer 
chromatography'' (``drugs-of-abuse'' is defined by the National 
Institute for Drugs of Abuse now National Substance Abuse and Mental 
Services Health Administration Laboratory Certification Program). This 
commenter also requested deletion of the requirement under Sec.  
493.1249(b) for at least one control sample to be processed and 
included in each chamber, stating that all environmental, chemical and 
material variables within a chamber are visualized by running 
calibration materials. The commenter added that controls should be 
analyzed with each run, and that each run should not exceed a 24 hour 
period.
    Response: We agree with the commenter that the control requirements 
formerly at Sec.  493.1249 are not clear; therefore, we are revising 
the language to clarify the requirements. We are moving the 
requirements for thin layer chromatography to Sec.  493.1256(d)(4) 
under Control procedures. In addition, we are revising the term ``drug 
abuse screening'' to read ``all known substances or drug groups'' 
identified and reported by the laboratory, to accommodate the wider use 
of the technology. However, we disagree with the commenter's statement 
that analyzing one control material per 24 hours is sufficient. If 
extractions and tests are performed more frequently than once per 24 
hours, each ``plate'' or ``card'' (formerly referred to as ``chamber'') 
must be spotted with at least one sample of control material to ensure 
that appropriate separation, and as applicable, extraction took place. 
The inclusion of a calibration material containing all known substances 
or drug groups reported by the laboratory using thin layer 
chromatography on each plate or card ensures appropriate identification 
of the substances or drugs in patient specimens.
Section 493.1253 Condition: Hematology
    Specific comments received and response to comments regarding Sec.  
493.1253 are set forth below.
    Comment: We received several comments requesting the deletion of QC 
requirements in hematology because they would increase laboratory 
costs.
    Response: We agree with the commenters that the requirement to 
include two levels of control material each 8 hours of testing for 
automated hematology analyzers (for example, cell counters and 
differential counters) is somewhat excessive in light of the proven 
stability and reliability of these instruments. Therefore, we are 
deleting the specialty-specific control requirement for automated 
hematology analyzers formerly at Sec.  493.1253(b), and are requiring 
laboratories to meet the general control requirements (now at Sec.  
493.1256(d)) when using automated hematology analyzers. However, the 
manufacturer's instructions and the laboratory's evaluation of the 
instruments' stability, environmental effects, and operator variance 
will determine the actual number, type, and frequency of testing 
control materials. At a minimum, the laboratories will have to test two 
control materials of different concentrations each day.
    Comment: One commenter requested that we remove the requirement for 
duplicative testing of patient and control specimens for manual 
coagulation tests, as required at Sec.  493.1253(d)(2), since 
proficiency testing requirements do not allow for duplicative testing.
    Response: We disagree with the commenter and are retaining the 
requirement for duplicative testing of patient specimens and control 
materials for manual coagulation testing (now at Sec.  493.1269(c)(2)). 
CLIA regulations for proficiency testing (PT) (Sec.  493.801(b)(2)) 
require the laboratory to test PT samples the same number of times that 
it routinely tests patients' samples. Therefore, since patient 
specimens must be routinely tested in duplicate, PT samples for manual 
coagulation testing must also be tested in duplicate.
Section 493.1257 Condition: Cytology and Section 493.1259 Condition: 
Histopathology
    Approximately 66 percent of the 1,030 comments received concerning 
the final rule with comment period,

[[Page 3665]]

subpart K, were in response to the cytology requirements. The comments 
were primarily from professional organizations, cytotechnologists, 
pathologists, and other physicians. The major issues that commenters 
addressed include--
    (1) Workload limits; (2) review of reactive reparative cases by a 
technical supervisor; (3) the 10 percent rescreen of negative cases 
screened by a cytotechnologist; and (4) the 5-year retrospective review 
of negative smears from patients with a current high grade lesion.
    Specific comments and response to comments regarding Sec. Sec.  
493.1257 and 493.1259 are set forth below.
    Comment: Several commenters stated the language ``non automated 
microscopic technique'' used to describe the slides that are counted in 
the workload limit is inappropriate and might be confused with slides 
that are screened using a motorized mechanical stage or with slides 
that are read by an automated instrument.
    Response: We agree with the commenters and are removing the wording 
``non automated microscopic technique.'' We also want to emphasize that 
slides that are read with a human component must be included in the 100 
slide limit; slides that are read by an automated instrument that do 
not require human review are not included in the workload limit.
    Comment: A number of commenters and one cytology organization were 
opposed to establishing the workload limit at 100 slides examined in a 
24 hour period. A few commenters felt the workload limit was too 
restrictive, while other commenters and the cytology organization 
indicated the limit was too high.
    Response: The CLIA statute at section 353(f)(4)(B)(i) specifically 
states that the standards must establish ``the maximum number of 
cytology slides that any individual may screen in a 24 hour period.'' 
Limiting the number of slides that may be examined in 24 hours to no 
more than 100 is the absolute maximum workload limit for an individual. 
However, we agree with the commenters that this may not be an 
appropriate workload for all individuals. To clarify our position, 
formerly at Sec.  493.1257(b)(1) (now at Sec.  493.1274(d)(2)), we 
specify that the Federal workload limit was not to be used as a 
performance target for cytology personnel. In addition, we specified 
formerly at Sec.  493.1257(c)(4) (now at Sec.  493.1274(d)(1)) that the 
cytology technical supervisor must establish a workload limit (not to 
exceed 100 slides examined per 24 hours) for each person examining 
slides and that at least every 6 months, the technical supervisor must 
re-evaluate and adjust, if necessary, each individual's workload limit. 
In addition, we are emphasizing that the workload limit applies only to 
individuals and does not apply to automated slide examination systems 
that may be used to screen slides and identify those smears requiring 
no human microscopic examination.
    Comment: One organization asked whether the workload requirements 
are applicable to technical supervisors or only to cytotechnologists. 
Several commenters suggested the workload requirement only applies to 
cytotechnologists.
    Response: The workload requirements apply to any individual who 
performs primary screening of cytology slides. This may be a technical 
supervisor or a cytotechnologist. We are also clarifying that while 
tissue pathology slides and previously examined gynecologic and 
nongynecologic slides are not included in the 100-slide workload limit 
for technical supervisors, the technical supervisor must subtract the 
time spent evaluating these slides and the time spent on any 
nonscreening duties from the time spent screening slides to 
appropriately adjust the workload.
    Comment: Many commenters and the cytology professional 
organizations opposed the workload provision to count as one-half slide 
those smears made using automated, semiautomated, or other liquid-based 
slide preparatory techniques that result in cell dispersion over one-
half or less of the slide. Some commenters indicated that this workload 
limit should apply only to nongynecologic preparations, while others 
thought it premature to use this calculation for any cytologic 
preparations until sufficient scientific studies have been completed to 
document the establishment of a workload limit appropriate for these 
preparatory techniques.
    Response: In order to address concerns of the commenters, we are 
making several clarifications. First, the 200-slide workload limit was 
initially established in the February 28, 1992 final rule with comment 
period published in the Federal Register (57 FR 7002) in response to 
innovations in cytology preparatory techniques and acknowledgment that 
slide preparations that only occupy a portion of the slide will not 
count as a whole slide. Slide preparations (gynecologic and 
nongynecologic) made using automated, semi-automated, or other liquid-
based preparatory techniques that result in a specimen that only 
occupies a small portion of the slide, are counted as one-half slide. 
Second, on January 19, 1993, we published a final rule with comment 
period in the Federal Register (57 FR 5212) removing gynecologic 
preparations. On July 22, 1993, we published a technical correction 
notice in the Federal Register (58 FR 39154) that inadvertently 
reinserted gynecologic preparations. In addition, Cytyc, manufacturer 
of ThinPrep TM, agrees that a 200-slide workload limit is 
too high for gynecologic preparations and has requested that the 200 
slide workload limit not be applicable to gynecologic slides. We agree 
with the commenters and Cytyc corporation, and we are eliminating 
gynecologic slides from the 200-slide workload limit (now at Sec.  
493.1274(d)(2)(iii)). The 200-slide workload limit will only apply to 
nongynecologic slides.
    Comment: Many Commenters and the Cytology organizations agreed that 
a workload limit was appropriate for gynecologic preparations. However, 
they were opposed to establishing a workload limit for nongynecologic 
smears because these preparations vary greatly in specimen type or 
source, preparatory techniques, and cellularity requiring various time 
frames for evaluation. The commenters acknowledged the difficulty in 
establishing a workload limit for individuals who examine 
nongynecologic preparations exclusively or a combination of gynecologic 
and nongynecologic smears. For fine needle aspirations, several 
organizations suggested using the methodology employed by New York 
State to prorate nongynecologic preparations, that is, for cases 
involving one to three slides, each slide is counted as one and for 
cases having four or more slides, a maximum of three slides are counted 
for workload purposes.
    Response: We agree with the commenters that it is easier to 
establish a workload limit for gynecologic smears than for 
nongynecologic preparations because of the variability in 
nongynecologic preparations; however, the statute requires us to 
determine the maximum number of cytology slides that an individual can 
screen in a 24-hour period. Therefore, the workload limit is applicable 
to all cytology slides, including gynecologic and nongynecologic 
preparations. Concerning the New York State proration of nongynecologic 
slides, this practice is no longer in use in New York.
    Comment: Several individuals asked for clarification on the 
specific guidelines that a technical supervisor should use to determine 
the maximum workload for an individual. Some

[[Page 3666]]

commenters noted the technical supervisor may have to justify a 
workload that is lower than 100 slides to hospital and laboratory 
administrators.
    Response: Formerly at Sec.  493.1257(c)(4)(i), individual workload 
is based on the performance evaluation described formerly at Sec.  
493.1257(c)(3). Therefore, we are revising the requirement, now at 
Sec.  493.1274(d)(1)(i), to make it more understandable. Performance 
must be evaluated using the following: (1) Re-evaluation of 10 percent 
of the cases interpreted to be negative by cytotechnologists; and (2) 
comparing the cytotechnologist's interpretation with the final 
diagnosis on cases of atypical squamous cells of undetermined 
significance (ASC-US), low-grade squamous intraepithelial lesion(LSIL), 
high-grade squamous intraepithelial lesion (HSIL), glandular epithelial 
cell abnormalities, or other malignant neoplasms. However, the 
evaluations listed in the former CLIA regulations must be viewed as 
minimal requirements and the laboratory may have additional mechanisms 
or criteria to evaluate individual performance. For example, the 
following provisions in the CLIA regulations may be used: (1) Number of 
discrepant findings on the retrospective review of previous negative 
cases from patients with a current HSIL, adenocarcinoma or other 
malignant neoplasm; (2) individual statistics evaluated against the 
laboratory's overall statistics; and (3) competency assessment 
activities.
    Comment: Many of the commenters and the cytology organizations 
suggested that the requirement for confirmation of cases by the 
technical supervisor be limited to those having atypical squamous or 
glandular cells, or any premaligment or malignant cell changes. The 
commenters suggested deleting the reference requiring confirmation of 
``reactive or reparative changes,'' stating that the requirement was 
excessive. Other commenters recommended changes to allow technical 
supervisors the discretion to determine the level of supervisions, that 
is, review of cases with benign cellular changes, needed by each 
employee. In addition, several commenters suggested we revise the 
language to include the Bethesda terminology.
    Response: We have not removed all reference to reactive and 
reparative changes because many laboratories still use this 
classification. The regulation, however, incorporates the Bethesda 
terminology, which provides for a uniform categorization of the 
cellular changes seen in gynecologic cytology. Most of the slides 
formerly classified as having ``reactive and reparative'' changes that 
would have exhibited marked or extensive cellular changes on technical 
review will, therefore, be classified as ASC-US or as having a squamous 
cell abnormality under the Bethesda terminology. As specified at Sec.  
493.1274(e), all of these slides are required to be reviewed by the 
technical supervisor. However, we have retained the classification 
reactive and ``reparative changes,'' and similar cellular changes under 
the Bethesda category ``Negative for Intraepithelial Lesion or 
Malignancy'' that would formerly have been categorized as reactive or 
reparative to encompass those slides needing review by the technical 
supervisor. Technical supervisors continue to have the discretion to 
review more cases as necessary to train and manage cytotechnologists 
under their supervision. Although we are not requiring the use of the 
Bethesda terminology, the majority of the laboratories have adopted it, 
and we encourage other to do the same.
    Comment: One organization stated that the technical supervisor's 
signature on the worksheet is acceptable documentation for the review 
of abnormal gynecologic cases. For nongynecologic cases, the 
organization suggested that laboratories allow the technical personnel 
to verify the final computer generated report that would include the 
name of the technical supervisor who reviewed the case. Another 
commenter asked for clarification on electronic signatures and whether 
CLIA regulations allow electronic requisitions.
    Response: We do not believe that any change in the CLIA regulations 
is appropriate. The final report must be verified by the technical 
supervisor who reviewed the case and signs the report, and electronic 
signatures must be authorized and verified by the technical supervisor 
who signs the report. As specified at Sec.  493.1241, electronic 
requisitions are acceptable, as long as the requisition contains the 
required information.
    Comment: Several commenters, including one cytology organization, 
disagreed with requiring laboratories to rescreen 10 percent of the 
cases interpreted to be normal or negative by cytotechnologists. One 
organization stated the 10 percent rescreen is a statistically invalid 
mechanism for reducing the false negative rate and suggested the 
requirement be replaced by a goal-oriented statistically valid system 
for promoting laboratory QC. One organization was opposed to requiring 
laboratories to complete the 10 percent rescreen before reporting 
patient results.
    Response: The CLIA statute requires ``* * * random rescreening of 
cytology specimens determined to be in the benign category * * *'' 
Accordingly, random rescreening of negative cases is required in CLIA 
rules. We view the 10 percent rescreen as a minimum requirement and 
only one component of the laboratory's control procedures and QA 
activities. In addition, rescreening is supported by the results of 
cytology surveys conducted under CMS contract that includes rescreening 
approximately 0.1 percent of the laboratory's caseload. In many of 
these surveys, diagnostic discrepancies were noted between the 
contractor's evaluation of patient specimens and the results reported 
by the laboratory, even though the sample rescreened was less than 10 
percent of the laboratory's caseload. The control procedures, including 
the 10 percent rescreen, assess the quality of the laboratory's 
results, and the rescreen must be completed before issuing patient 
reports on the slides selected for the 10 percent rescreen as specified 
formerly at Sec.  493.1257(d)(1)(iii) (now at Sec.  
493.1274(c)(1)(ii)).
    Comment: One commenter asked whether the 10 percent re-evaluation 
of negative cases could be performed by the same individual who 
performed the primary review.
    Response: The 10 percent rescreen of negative cases is one 
provision of the cytology control procedures specified formerly at 
Sec.  493.1257(d) requiring laboratories to have a program designed to 
detect errors in cytology examinations. This provision is now at Sec.  
493.1274(c). Ten percent of the cases interpreted as negative by 
cytotechnologists must be reevaluated by a cytology technical 
supervisor qualified under Sec. Sec.  493.1449(b) or 493.1449(k), a 
cytology general supervisor qualified under Sec.  493.1469(b)(2), or a 
cytotechnologist qualified under Sec.  493.1483 who has the experience 
specified in Sec.  493.1469(b)(2). For laboratories with a solo 
pathologist (no cytotechnologists), the 10 percent rescreen need not be 
performed; however, the following cytology QC procedures must be 
performed: a laboratory comparison of clinical information and 
histopathology reports (as specified at Sec.  493.1274(c)(2)), a 
retrospective rescreen of normal and negative cases received within the 
previous 5 years from a patient with a current high grade lesion (as 
specified at Sec.  493.1274(c)(3)) and annual statistical evaluation 
(as specified at Sec.  493.1274(c)(5)).

[[Page 3667]]

    Comment: Many cytology organizations disagreed with requiring 
review of all normal or negative slides from the previous 5 years for 
any patient having a current high grade intraepithelial lesion or 
above. The commenters felt that the 5-year review was unreasonable and 
unnecessarily burdensome and suggested that the review include only the 
two most recent smears, if available in the laboratory. A number of 
commenters noted the error at Sec.  493.1257(d)(3) in referring to 
patients with ``a current high grade or above intraepithelial lesion . 
. .'' and suggested rewording the requirement for retrospective review 
of negative cases from patients having a ``current high grade 
intraepithelial lesion or cancer.''
    Response: We are not reducing the requirement for review of 
negative cases from the previous 5 years for patients having a current 
high grade intraepithelial lesion or cancer because the law requires 
``. . . for each abnormal cytological result, rescreening of all 
(emphasis added) prior cytological specimens for the patient, if 
available.'' However, we appreciate and agree with the commenters' 
suggestion about rewording the requirement, formerly at Sec.  
493.1257(d)(3) (now at Sec.  493.1274(c)(3)) to reflect current 
terminology.
    Comment: One organization asked for clarification on the time frame 
for completion of the retrospective review of cases with a current high 
grade lesion or above and the histology and cytology correlation.
    Response: The retrospective review and the histology and cytology 
correlation are part of the control procedures and must be completed in 
a timely manner. Since there is a possibility that this QC activity 
could result in the issuance of a corrected report that may affect 
patient treatment, the laboratory must have procedures in place that 
include time frames for these activities.
    Comment: Several commenters and cytology organizations disagreed 
with requiring laboratories to compare the case reviews of each 
individual with the laboratory's overall statistical values. The 
commenters stated that the case mix (specimens from various clinics 
with different patient populations) varies and these statistics should 
not be used to assess individual performance. In smaller laboratories 
the statistical comparison may not be valid due to the small numbers. 
It was suggested that laboratories be given flexibility to determine 
the best approach for implementing the control procedure requirements 
and evaluating individual performance.
    Response: We established these requirements as a result of comments 
provided in response to the proposed rule that was published on May 21, 
1990 in the Federal Register (55 FR 20896). The commenters stated that 
reviewing the laboratory's data provided useful information on overall 
laboratory practice as well as individual performance. We believe these 
requirements have provided valuable information for assessment of 
laboratory and individual performance; therefore, we are not making any 
revisions. However, laboratories may document situations that affect 
the laboratory's statistics and individual case reviews.
    Comment: One cytology organization was opposed to requiring 
laboratories to document cases for which histologic reports were 
unavailable for comparison with abnormal gynecologic results, stating 
that it was time consuming and burdensome and provided no benefit to 
the patient.
    Response: In an attempt to minimize the burden, (now at Sec.  
493.1274(c)(5)(iv)), we are requiring documentation of only the number 
of cases that have histology correlation. We believe this information 
is necessary to determine the laboratory's success in obtaining 
histology reports for the histology and cytology correlation.
Section 493.1259 Condition: Histopathology
    Specific comments received and response to comments regarding Sec.  
493.1259 are set forth below.
    Comment: Two medical professional organizations disagreed with the 
requirements at Sec.  493.1259(c) that precluded neurologists from 
examining nerve and muscle biopsies. Also, in May 1993, CLIAC 
recommended that neurologists with specialized training and board 
certification qualify as technical supervisors, general supervisors, 
and testing personnel of neuromuscular histology. Without recognition 
of this training, neurologists would be required to refer neuromuscular 
tissue specimens to an anatomic pathologists for examination.
    Response: We are amending the histopathology QC requirements 
formerly at Sec.  493.1259(c) (now at Sec.  493.1273(c)) to allow 
individuals who have successfully completed a training program approved 
by HHS to examine and provide reports for neuromuscular pathology. In 
Appendix C of the State Operations Manual (CMS Pub. 7), subpart K, we 
will specify that the training program developed by the American 
Academy of Neurology Committee for Neuromuscular Pathology is approved 
by HHS. We are making the change to Sec.  493.1273 rather than the 
personnel requirements in subpart M, because in this final rule, we are 
limiting the personnel revisions to the phase-in provisions addressed 
in the December 28, 2001 proposed rule. HHS received numerous personnel 
comments in response to the February 28, 1992 final rule with comment 
period which we intend to address in a future regulation.
Section 493.1265 Condition: Histocompatibility
    Specific comments received and response to comments regarding Sec.  
493.1265 are set forth below.
    Comment: Several commenters were pleased with the final CLIA rule 
for histocompatibility testing and felt the majority of the concerns 
raised over the proposed rule had been addressed. They noted the 
requirements now generally reflect the state of the art laboratory 
practices in this specialty area of testing that is continuing to 
evolve.
    Response: We appreciate this acknowledgment of the efforts made in 
developing the histocompability QC requirements specified in the final 
rule with comment period that was published on February 28, 1992 in the 
Federal Register (57 FR 7170). In our continuing endeavor to represent 
current technology and practice, we are updating some of the 
terminology and references used in this section. We are also deleting 
several requirements that are duplicative of requirements found 
elsewhere in the CLIA regulation. In addition, we are adding clarifying 
language and reorganizing the requirements in this section that apply 
to HLA typing, disease associated studies, antibody screening, 
crossmatching, transplantation, and general requirements that apply to 
every histocompatibility laboratory regardless of the testing and 
services offered by the laboratory.
    Comment: One commenter requested the requirements for 
histocompatibility testing be separated into three groups: solid organ 
transplantation, including renal; bone marrow transplantation; and 
histocompatibility testing for transfusion services.
    Response: We acknowledge that the organization of the 
histocompatibility requirements found in the final rule with comment 
period may have caused some confusion to the reader trying to determine 
what testing requirements apply to each type of organ or tissue 
transplant. While there are various ways to group the requirements in 
this specialty, we are reorganizing this section by first delineating 
the general requirements for histocompatibility

[[Page 3668]]

testing (now at Sec.  493.1278(a)) and specifying the requirements for 
HLA typing (now at Sec.  493.1278(b)), disease associated studies (now 
at Sec.  493.1278(c)), antibody screening (now at Sec.  493.1278(d)), 
crossmatching (now at Sec.  493.1278(e)) and transplantation (now at 
Sec.  493.1278(f)). In addition, we believe this reorganization, along 
with other revisions, will greatly enhance the readability of this 
section and clarify the requirements that must be met for each type and 
level of histocompatibility testing performed by the laboratory.
    Comment: One commenter pointed out the requirement at Sec.  
493.1265(a)(4) that addresses reagent typing sera inventories prepared 
in-house should also require that the specificity of the reagent be 
indicated. The commenter also requested clarification of the term 
``typing tray'' used at Sec.  493.1265(a)(9)(i) since the term can 
refer to any 96, 72, or 60 well microtiter tray used in the HLA 
laboratory. The commenter stated that without clarification, it is 
unclear whether the control requirements specified at this requirement 
refer only to trays used for HLA typing or if they include trays run in 
an attempt to identify the presence of circulating HLA antibodies.
    Response: We agree that reagent specificity must be indicated on 
the laboratory's in-house prepared reagent typing sera inventory and 
are amending the requirement now at Sec.  493.1278(a)(3) accordingly.
    The commenter is correct to question the scope of the requirement 
formerly at Sec.  493.1265(a)(9)(i) that addressed control requirements 
for typing trays. In addition, the term ``typing tray'' is somewhat 
restrictive in that testing performed with newer and emerging 
technologies may not necessarily use microtiter trays. Therefore, we 
are revising the requirement for clarification, and, with the 
reorganization of this section, Sec.  493.1278(b)(6) now describes the 
controls a laboratory must use for each HLA typing, and Sec.  
493.1278(d)(6) addresses the controls a laboratory must use when 
performing antibody screening.
    Comment: One commenter requested that the CLIA regulations mandate 
HLA antibody identification when panel screening studies indicate the 
presence of a lymphocyte-reactive antibody. In addition, the laboratory 
should determine if this is an autoantibody or alloantibody. The 
commenter also requested the CLIA rule require that the specific 
technique used in HLA antibody screening be at least as sensitive as 
the complement-dependent lymphocytotoxicity technique used in the final 
donor crossmatch.
    Response: Histocompatibility testing is a rapidly evolving, highly 
complex specialty. Its role in predicting long-term allograft survival 
is the subject of numerous research studies. Not all antibody reactions 
have a defined specificity, and the clinical relevancy of each antibody 
has not been established. Mandatory antibody identification may be 
impractical, if not impossible, and uninformative in these cases. 
However, we agree that antibody identification must be performed when 
appropriate to support clinical transplant protocols and Sec.  
493.1445(e)(3)(i) requires the laboratory director to select test 
methods that are capable of providing the quality of results required 
for patient care. It is the laboratory director's responsibility to 
institute more stringent testing protocols as necessary for quality 
patient care. Therefore, we are adding a requirement at Sec.  
493.1278(d)(7) for laboratories that perform antibody identification to 
have available and follow written criteria and procedures for antibody 
identification to the level appropriate to support clinical transplant 
protocol.
    We agree with the commenter that the laboratory must use a 
technique that detects HLA-specific antibody with a specificity 
equivalent or superior to that of the basic complement-dependent 
microlymphocytotoxicity assay. In addition, to detect antibodies to HLA 
Class II antigens, the laboratory must use a method that distinguishes 
antibodies to HLA Class II antigens from antibodies to Class I 
antigens. We are adding these two new requirements at Sec. Sec.  
493.1278(d)(1) and 493.1278(d)(2).
    To ensure quality laboratory practices and for consistency with the 
two new requirements, we are specifying that techniques used for 
crossmatching must be documented to have increased sensitivity in 
comparison with the basic complement-dependent microlymphocytotoxicity 
assay (now at Sec.  493.1278(e)(1)). In addition, when performing HLA 
typing, the laboratory must use a technique that is established to 
optimally define, as applicable, HLA Class I and II specificities (now 
at Sec.  493.1278(b)(1)).
    Comment: A number of commenters were opposed to the elimination of 
mandatory monthly screening for HLA antibodies, since most, if not all, 
laboratories lack access to accurate information regarding each 
potential transplant recipient's exposure to sensitizing events. This 
is compounded by the probability that not all potentially sensitizing 
events have been identified. A few commenters acknowledged that the 
cost of monthly screening can be prohibitive and suggested there may be 
some instances when monthly screening may not be necessary. However, 
most commenters agreed that studies need to be done to determine the 
optimum frequency of antibody screening.
    Response: We agree with the commenters and recognize the importance 
of developing an accurate immunological history of the potential 
transplant recipient and the difficulty of identifying and obtaining 
information on all potential sensitizing events. We also appreciate the 
efforts to control healthcare costs by eliminating unnecessary and or 
redundant testing. To provide flexibility and allow responsiveness to 
emerging research data and information, we are revising the 
requirements formerly at Sec. Sec.  493.1265(a)(2)(ii) and (a)(8)(i) 
(now at Sec. Sec.  493.1278(d)(4) and (d)(5)) to require the laboratory 
to make a reasonable attempt to have available monthly serum specimens 
for all potential transplant recipients for periodic antibody screening 
and crossmatch. In this regard, the laboratory must have available and 
follow a policy, consistent with clinical transplant protocols for the 
frequency of screening potential transplant recipient sera for 
preformed HLA-specific antibodies.
    Comment: Three commenters noted that DNA typing involves the genes 
rather than the expressed antigens; therefore, Sec.  493.1265(a)(10) 
would be more accurate if changed to read, ``Compatibility testing for 
HLA class II polymorphisms should utilize techniques, for example, 
mixed lymphocyte culture, homozygous typing cells, or DNA analysis.''
    Response: We agree with the commenters that the wording of the 
requirement formerly at Sec.  493.1265(a)(10) is somewhat inaccurate 
and also believe that the requirement may be too restrictive for future 
methodologies, technologies, and transplantation protocols. Therefore, 
we are deleting this requirement for the laboratory to use specific 
techniques, for example, mixed lymphocyte cultures, to determine HLA 
Class II incompatibilities.
    Comment: One commenter stated that the requirement at Sec.  
493.1265(a)(13) to have histocompatibility testing personnel evaluate 
unknowns on a monthly basis is excessive and should be reduced to once 
every 6 months.
    Response: Histocompatibility testing is a highly complex specialty 
with great potential for harm to the patient if the testing is 
incorrectly performed. CLIA regulations specify formerly at

[[Page 3669]]

Sec.  493.1445(e)(13) that the director has to ensure that policies and 
procedures are established for monitoring employee competency and to 
identify needs for remedial training or continuing education. 
Monitoring employee competency may include the evaluation of previously 
tested specimens as unknowns. However, we are deleting this former 
requirement at Sec.  493.1265(a)(13) because we believe it is somewhat 
duplicative of the laboratory director responsibility.
    Comment: Three commenters, including a professional organization, 
recommended that living transplants be deleted from Sec.  
493.1265(b)(2) that requires the performance of mixed lymphocyte 
cultures or other augmented testing to evaluate HLA class II 
compatibility. The commenters stated that although appropriate for bone 
marrow transplantation, mixed lymphocyte culture is performed rarely in 
living-related kidney transplantation where HLA Class II compatibility 
and genetic linkages can be adequately determined using serological 
methods. In addition, the commenters maintained that mixed lymphocyte 
culture tests were unnecessary in solid organ transplants and not 
considered a contraindication to this type of transplantation.
    Response: We agree with the commenters. The phrase, ``and living 
transplants,'' formerly at Sec.  493.1265(b)(2), was deleted in a 
technical correction notice published on January 19, 1993. In addition, 
we recognize the evolving nature of transplant medicine makes it 
difficult to prescribe standards for testing protocols that may be 
quickly outdated with emerging research data and information, for 
example, graft survival, acute, and chronic rejection. For this reason 
we are revising the requirements formerly at Sec. Sec.  493.1265(b) and 
(c) that specified the type of testing to be performed for each 
transplant type. We are requiring (now at Sec.  493.1278(f)(1)) that 
laboratories performing histocompatibility testing for transfusion and 
transplantation purposes have available, and follow, written policies 
and protocols specifying the histocompatibility testing to be performed 
for each type of cell, tissue, or organ to be transfused or 
transplanted. The laboratory's policies must address, as applicable, 
testing protocols for cadaver donor, living, living-related and 
combined organ and tissue transplants; the level of testing required to 
support clinical transplant protocols (for example, HLA typing at the 
antigen or allele level); and any additional testing required for 
patients at high risk for allograft rejection. In addition, we believe 
this less prescriptive, but laboratory-specific requirement provides 
the flexibility required to ensure laboratory practice that is 
responsive to advances in transplantation medicine and laboratory 
methodologies and technology.
    Comment: One commenter stated that the requirement, at Sec.  
493.1265(b)(3), to provide the results of the final crossmatch before 
nonrenal solid organ transplantation when the recipient has 
demonstrated presensitization is not necessarily relevant or realistic 
for all types of grafts. The commenter cited the short viability time 
of certain organs (heart and lung) and unpublished data pertaining to 
the nonrelationship between high-titered positive donor T cell 
crossmatches and liver allograft survival.
    Response: We agree with the commenter that the period of time that 
organs, for example, the liver, pancreas, and heart remain viable after 
removal from the donor is often not sufficient for the laboratory to 
complete the crossmatch. The regulation formerly at Sec.  
493.1265(b)(3) (now at Sec.  493.1278(f)(3)) has been revised to 
require laboratories to develop and follow policies for testing and 
providing results of final crossmatches when the recipient has 
demonstrated presensitization by prior serum screening. In addition, 
the policy must address emergency transplant situations that would not 
allow time for the laboratory to perform prospective crossmatches. In 
addition, we would like to clarify that the intent of Sec.  
493.1278(f)(3) is not to preclude the use of crossmatch-positive 
nonrenal organs and tissues but to ensure, whenever possible, the 
availability of all pertinent test results on which the physician(s) 
may base their decision to proceed with the transplant.
Section 493.1267 Condition: Clinical Cytogenetics
    Specific comments received and response to comments regarding Sec.  
493.1267 are set forth below.
    Comment: One commenter suggested the cross-references to subpart K 
at Sec.  493.1267 list only those portions that apply to cytogenetic 
testing so that, for example, the general requirement for testing 
positive and negative controls is not referenced. The commenter 
suggested at the very least, Appendix C (Survey Procedures and 
Interpretative Guidelines for Laboratories and Laboratory Services) of 
the State Operations Manual (CMS Pub. 7) should instruct CLIA surveyors 
to ignore this requirement when inspecting a cytogenetics laboratory.
    Response: The task of delineating all applicable requirements of 
subpart K for each specialty or subspecialty of testing would require 
continuous revision and updating for new test systems and emerging 
technologies. For this reason, the requirement (now at Sec.  493.1225) 
remains unchanged and continues to direct laboratories to comply with 
the requirements of subpart K that are applicable to the testing being 
performed. However, Appendix C of the State Operations Manual will give 
guidance to surveyors concerning the control requirements for clinical 
cytogenetics. As specified now at Sec.  493.1256(e)(2), each day of 
use, the laboratory is required to test the positive and negative 
reactivity of staining materials to ensure predictable staining 
characteristics. Media must be checked for sterility and to ensure that 
it supports growth of the appropriate tissues as required now at Sec.  
493.1256(e)(4). As for materials to demonstrate chromosome 
abnormalities, for example, linkage, breakage, or translocation, 
Appendix C of the State Operations Manual (CMS Pub. 7) states that 
these materials are not routinely available; however, an alternative 
procedure for the immediate assessment and monitoring of all testing 
over time must be instituted by the laboratory as specified now at 
Sec.  493.1256(h).
    Comment: A few commenters stated laboratory testing of sex 
chromatin by Barr body analysis or by ``Y'' body analysis is not 
considered the standard of practice for the diagnosis of individuals 
with sex chromosome aneuploidy, citing the well documented frequency of 
mosaicism in individuals with sex chromosome aneuploidy that leads to 
false negatives. Therefore, they strongly recommend not employing this 
testing as a screening test and deleting it from the list of tests that 
are performed in cytogenetics laboratories.
    Response: We agree with the commenters and are deleting the 
requirements pertaining to the performance of X and Y chromatin counts 
for sex determination that were formerly at Sec.  493.1267(a). In this 
final rule at Sec.  493.1276(c), we are now requiring full chromosome 
analysis for sex determination.
    Comment: A few commenters questioned the requirement that 
chromosome resolution be sufficient to support the reported result. One 
commenter stated that this is a ``catch 22'' in that a low resolution 
study reported as normal in a patient with an abnormality only 
detectable at a higher level of resolution would be wrong, however, the 
low resolution analysis would be in support of the reported

[[Page 3670]]

normal diagnosis. The commenters suggested establishing a specific band 
level of resolution that would be dependent upon the type of study 
requested.
    Response: We are revising the requirement formerly at Sec.  
493.1267(b) (now Sec.  493.1276(b)(2)) for clarity. The requirement now 
states that the resolution used must be appropriate for the type of 
tissue or specimen, and that the type of study required is based on the 
clinical information provided to the laboratory.
    Comment: One commenter suggested that substituting the words 
``photographic karyotypes'' for ``photographs'' would correctly reflect 
what cytogeneticists read.
    Response: We are adding new language to the CLIA regulation 
formerly at Sec.  493.1267(c) (now at Sec.  493.1276(a)) to specify 
karyotypes in addition to photographs.
    Comment: A few commenters disagreed with the CLIA regulation 
requiring ``appropriate nomenclature'' and felt the CLIA regulation 
should require the use of the International System of Cytogenetic 
Nomenclature in reporting all cases because it is the only recognized 
system that exists and anything else would be homemade and impossible 
to interpret other than by that particular laboratory.
    Response: We agree with the commenters and are replacing the words 
``appropriate nomenclature'' formerly at Sec.  493.1267(d) (now at 
Sec.  493.1276(d)) with the words ``the International System of 
Cytogenetic Nomenclature.''
    Comment: One commenter stated that failure rate is an aspect of 
cytogenetic testing and that it is not addressed by CLIA regulations. 
The commenter also stated that failure rate can provide valuable 
information about a laboratory's capabilities and be easily evaluated 
by an individual lacking specific expertise in cytogenetics. The 
commenter stated that accepted standards for study failure rates exist 
for the various types of tests done in cytogenetic laboratories.
    Response: We agree that study and culture failure rates can be a 
useful tool in evaluating a cytogenetic laboratory's performance. 
However, the study must be evaluated carefully because many factors 
outside of the laboratory's control may influence the rates, for 
example, specimen transit time and conditions. In addition, what 
constitutes failure must be clearly defined. For this reason, we are 
not mandating failure rates but encourage laboratories to monitor these 
rates as part of a QA program.
    Comment: One commenter recommended gestational alpha-fetoprotein 
(AFP) be recognized as an analyte. Gestational AFP testing should not 
be included under Immunology, where AFP is used as a tumor marker.
    Response: Although the analyte alpha-fetoprotein may be used for 
genetic screening, the test does not entail chromosomal examination 
(that is, cytogenetics). Measurement of this analyte may be used for 
non-cytogenetic purposes. CLIA certifies laboratories in both the 
subspecialty of routine chemistry and general immunology for 
gestational and maternal AFP.
Section 493.1273 Standard: Immunohematological Collection, Processing, 
Dating Periods, Labeling and Distribution of Blood and Blood Products
    Specific comments received and response to comments regarding Sec.  
493.1273 are set forth below.
    Comment: One commenter requested the addition of requirements to 
Sec.  493.1273 regarding the use of bar code systems for the 
identification of blood and blood products, stating that laboratories 
should document the accuracy of bar codes before putting the systems 
into use, and as a continuing part of quality assurance while the 
systems are in use.
    Response: We agree with the commenter that the accuracy and ongoing 
reliability of bar code systems used for the identification of blood 
and blood products is an important quality issue for laboratories that 
use them. Laboratories involved in collecting, processing, dating, 
labeling, testing, and distributing blood and blood products are 
required to conform to the FDA requirements for blood and blood 
products at 21 CFR parts 606, 640, 21 CFR 610.40, and 610.53. 
Specifically, 21 CFR 606.121: Container label, permits the use of 
container labels that bear encoded information in the form of machine-
readable symbols approved for use by the Director, Center for Biologics 
Evaluation and Research, FDA, and refers to FDA's ``Guideline for 
Uniform Labeling of Blood and Blood Components,'' that addresses blood 
product labeling requirements, including standards for bar codes. Also, 
21 CFR 606.140 requires the laboratory to have control procedures that 
provide for monitoring the reliability, accuracy, precision, and 
performance of laboratory test procedures and instruments.
    Comment: A laboratory surveyor asked why CLIA personnel are 
responsible for surveying large sections of the FDA's regulations. 
Since CLIA is a self-funded program, the commenter wondered if the FDA 
reimbursed the CLIA program for these services.
    Response: The commenter is correct in questioning the role of the 
CLIA surveyors' inspection responsibilities. We have corrected the 
citations from 21 CFR to specify in 42 CFR part 493 the exact 
requirements that must be met under the CLIA regulations. The revised 
citations are now at Sec. Sec.  493.1105(a)(1)(i), 493.1271(a)(1) and 
(b). When reviewed, the actual time expended surveying sections of the 
FDA's regulation was minimal. Sister agencies such as the FDA and CMS 
frequently assist one another without charge when expenditures to 
provide such assistance are de minimis.

Subpart M--Personnel for Moderate Complexity (Including the 
Subcategory) and High Complexity

    In the February 28, 1992 final rule with comment period, the 
personnel requirements are located in subpart M and include 
qualification requirements for individuals to direct a laboratory 
performing high complexity testing. A phase-in period was provided for 
individuals with a doctoral degree to obtain board certification. In 
response to the publication of the date extension rules, we received 
comments suggesting that we develop alternative provisions to qualify 
individuals with a doctoral degree on the basis of laboratory training 
or experience, instead of requiring board certification. On December 
28, 2001, we published a proposed rule in the Federal Register (66 FR 
67163) that included provisions to end the phase-in period and revise 
and expand the qualifications required for an individual with a 
doctoral degree to direct a laboratory performing high complexity 
testing.
    Following publication of the proposed rule, we received 113 comment 
letters, which contained approximately 300 comments. Of these, 168 
comments agreed with one or more provisions in the proposed rule, 120 
comments disagreed with at least one of the provisions, 6 comments 
addressed the education requirements, and 1 comment reflected 
misinterpretation of the proposed requirements. Fifty-three of the 113 
comment letters specifically addressed qualification requirements for 
directors of laboratories performing histocompatibility testing.
    Specific comments received and responses to comments regarding the 
proposed rule are set forth below.
    Comment: The majority of the comments on the first provision (at 
the proposed and former Sec.  493.1443(b)(3)(i)) agreed with requiring 
board certification

[[Page 3671]]

as a qualification requirement for individuals having a doctoral degree 
to serve as high complexity laboratory directors. These commenters 
emphasized the role of board certification in ensuring that individuals 
have specific training and experience, as well as uniform and broad-
based clinical knowledge, skills and competencies. In addition, at the 
CLIAC meeting held on January 30, 2002 through January 31, 2002, CLIAC 
expressed strong support for board certification for laboratory 
directors and suggested the recent efforts of the boards to provide 
more flexible routes to certification would allow more individuals to 
meet the certification requirements. CLIAC and other commenters also 
felt that the documentation of continuing education required for 
retaining board certification is essential in ensuring that individuals 
maintain the professional abilities needed to direct laboratories that 
provide services in the multifaceted, constantly changing high 
complexity testing category. The few comments opposed to board 
certification indicated certification does not ensure the performance 
of individuals and that employee skill validation is the responsibility 
of the employer. These commenters also noted the absence of evidence 
documenting that certified individuals perform better than noncertified 
individuals.
    Response: We agree with the comments supporting board certification 
and are maintaining the former requirements at Sec.  493.1443(b)(3)(i) 
requiring board certification as one of the pathways for qualifying 
individuals with a doctoral degree as directors of laboratories 
performing high complexity testing. Although certification does not 
provide absolute assurance that individuals will effectively fulfill 
the responsibilities required of directors, it is a recognized 
benchmark of competency and an appropriate mechanism for qualifying 
individuals to serve as laboratory directors. In addition, the ongoing 
continuing education required by each of the HHS-approved boards to 
retain certification helps ensure these individuals maintain a current 
knowledge base.
    Comment: A State Health Department and one laboratory professional 
organization requested that all HHS-approved boards and the criteria 
for board approval be listed in the regulations. One of these 
commenters asked whether the phrase ``* * * be certified and continue 
to be certified * * *'' included in the proposed rule at Sec.  
493.1443(b)(3)(i) means that HHS will require board recertification 
when required by an HHS-approved board. In addition, a few commenters 
disagreed with board recertification.
    Response: A total of eight certification boards have been approved 
by HHS. Four boards are listed in the former regulations at Sec.  
493.1443(b)(3)(i): The American Board of Medical Microbiology; the 
American Board of Clinical Chemistry; the American Board of 
Bioanalysis; and the American Board of Medical Immunology. On July 8, 
1996, we published a notice in the Federal Register (61 FR 35736), that 
announced HHS approval of two boards: The American Board of 
Histocompatibility and Immunogenetics and the American Board of Medical 
Genetics. In this final rule, we are announcing HHS-approval of two 
additional boards: the National Registry for Clinical Chemistry at the 
doctoral level and the American Board of Forensic Toxicology. However, 
in this final rule, we are deleting the reference at Sec.  
493.1443(b)(3)(i) to the specific boards approved by HHS. Currently, 
all HHS-approved boards are listed on the Internet at http://www.cms.hhs.gov/clia/dirc/con.asp. In the future, boards approved by 
HHS will also be listed in Appendix C of the State Operations Manual 
(CMS Pub. 7), subpart M. Removing the list of approved boards from the 
regulations and placing the list in Appendix C will allow greater 
flexibility to update the list of HHS-approved boards.
    In response to the comments suggesting that the criteria for 
determining HHS-approval of certification boards be included in the 
regulations, we do not believe that regulations, which specify 
standards that must be met by covered entities, should include details 
of an administrative process. All boards approved by HHS have been 
determined to have comparable certification requirements. In the 
``Conditions for Coverage of Services of Independent Laboratories'' 
published in the September 19, 1974 Federal Register (39 FR 33693), the 
laboratory director qualification requirements included provisions for 
qualifying individuals with a doctoral degree. One option was 
certification by one of three boards (American Board of Medical 
Microbiology, the American Board of Clinical Chemistry, and the 
American Board of Bioanalysis). Subsequently, all boards approved by 
HHS have been determined to have certification requirements comparable 
to those three boards originally recognized. Any board may request HHS 
approval by submitting their request for board certification to CMS. 
This information will be evaluated to determine if the board's 
certification requirements are comparable to those currently approved 
boards.
    With respect to requiring recertification, it was always the intent 
of the former regulations, that individuals with a doctoral degree 
qualifying under Sec.  493.1443(b)(3)(i) must be, and continue to be, 
certified by an HHS-approved board. If a board requires recertification 
and an individual fails to recertify and loses board certification, 
this individual would no longer meet the director qualification 
requirement at Sec.  493.1443(b)(3)(i). In this final rule, and as 
proposed in the December 28, 2001 proposed rule, we are revising the 
language at Sec.  493.1443(b)(3)(i) for clarification.
    Comment: A number of comments agreed with the second provision (at 
proposed Sec.  493.1443(b)(3)(ii)) allowing individuals having a 
doctoral degree, who are serving or have served as directors of 
laboratories performing high complexity testing under the current 
regulations' phase-in provision, to continue to qualify without 
obtaining board certification. However, a few commenters felt this 
provision should be temporary, with a date specified by which board 
certification would be required to maintain qualification. One 
commenter urged that a date be established (and not extended) to 
conclude this qualification provision. A State Health Department 
interpreted the requirements in this provision to mean that a total of 
4 years of experience is required, and that the training and experience 
and director and/or supervisory experience cannot be gained 
concurrently. This commenter also suggested this experience be 
postdoctoral experience.
    Response: We agree the second proposed qualification provision is 
needed to allow (``grandfather'') individuals who have served or are 
currently serving as directors of high complexity testing to continue 
to serve. We also agree that a date needs to be specified to conclude 
this qualification pathway and the training and experience requirements 
clarified; however, we do not agree that the training and experience 
must be postdoctoral. We believe laboratory training and experience 
obtained while an individual is working toward obtaining a doctoral 
degree is pertinent and appropriate, and should be considered as 
meeting the requirement.
    In this final rule, at Sec.  493.1443(b)(3)(ii), we are specifying 
February 24, 2003, as the effective date

[[Page 3672]]

for this final rule's personnel qualification requirements, and we are 
clarifying the training and experience requirements individuals must 
meet. To ensure a smooth transition to the new provisions for directors 
of high complexity testing who are not board certified (but who have 
doctoral degrees), we will not be holding facilities out of compliance 
with the provisions of the rule concerning directors who are not board 
certified until the effective date of this new rule, to the extent the 
facilities are otherwise in compliance with the requirements for 
laboratory directors. Individuals must, therefore, as of February 24, 
2003, have at least 2 years of training or experience, or both; and 2 
years of experience directing or supervising high complexity testing.
    Comment: Several commenters (including one laboratory professional 
organization and one certification board) felt continuing education 
should be added as a requirement to the second proposed provision.
    Response: We acknowledge that continuing education is important; 
however, the proposed rule did not include a continuing education 
component for this provision. In addition, when ``grandfathering'' 
individuals who are serving or who have served in a particular 
position, minimum qualification requirements are considered so as not 
to disenfranchise these individuals. Finally, while regulations specify 
minimum requirements, States, accreditation organizations, and 
certification boards may establish more stringent requirements.
    Comment: The majority of the commenters were opposed to including 
the third provision (at proposed Sec.  493.1443(b)(3)(iii)). While 
there was general agreement that training and experience is essential 
for direction of high complexity testing, a few commenters (including a 
certification board and a laboratory professional organization) noted 
that training and experience vary greatly and it would be inappropriate 
to use training and experience as sole criteria to qualify individuals 
with a doctoral degree to direct high complexity testing. CLIAC also 
recommended that this provision be eliminated because it would not 
provide adequate documentation of the knowledge and skills needed for 
directorship of high complexity testing, lacks a mechanism to ensure 
continued competency, and is not commensurate with the high complexity 
laboratory director responsibilities. Several commenters noted that 
this proposed qualification pathway might result in an increase in the 
quantity of individuals qualified to direct high complexity testing at 
the expense of quality, which is in part attributed to a competent 
workforce. Although a few commenters agreed with this proposed 
provision to provide qualification specifications based on training and 
experience in lieu of board certification, they suggested revisions to 
make the provision more stringent and felt continuing education should 
be added to ensure that individuals maintain competency.
    Response: We agree with the comments expressing disagreement with 
the third proposed qualification pathway and are not including it in 
this final rule. Although high complexity procedures comprise less than 
20 percent of the laboratory procedures categorized, these are the most 
complex tests requiring a broad-based knowledge and the highest skills 
to fulfill the director responsibilities (formerly at Sec.  493.1445) 
and ensure quality testing. Therefore, we believe the knowledge and 
training of a high complexity laboratory director with a doctoral 
degree can best be demonstrated through board certification. In 
addition, in the former regulations, we provided phase-in qualification 
requirements that allow individuals with a doctoral degree to qualify 
based on training and experience in lieu of board certification until 
the specified expiration date. As mentioned earlier, on five separate 
occasions, we extended the phase-in provision to allow time for 
directors who were not board certified to complete the certification 
requirements and for HHS to review and approve certification boards. 
During the 10 years the phase-in provision has been in affect, HHS has 
approved five additional boards and we believe sufficient time has been 
provided for individuals to become aware of the board certification 
requirement. Moreover, recent efforts of certification boards have 
provided additional routes to certification, allowing more individuals 
to meet the certification requirements.
    In this final rule, board certification will be required for an 
individual with a doctoral degree seeking to become a high complexity 
laboratory director on and after February 24, 2003. However, as 
previously mentioned, we are allowing individuals, who qualified under 
the phase-in provision and are now serving or have served as directors 
of laboratories performing high complexity testing, to continue to 
serve as laboratory directors.
    Comment: A few commenters disagreed with requiring a doctoral 
degree as the minimum education requirement for directors of 
laboratories performing high complexity testing. They suggested that 
individuals with an appropriate master's degree and progressive 
experience in the clinical laboratory (5 to 10 years) should be able to 
qualify.
    Response: We believe the doctoral degree is an appropriate minimum 
education requirement for directors of laboratories performing high 
complexity testing. It is commensurate with the responsibilities of a 
high complexity laboratory director, as specified in the former 
regulations at Sec.  493.1445, and consistent with the education 
requirements and responsibilities specified for the other laboratory 
personnel categories described in subpart M of the regulations.
    Comment: Several commenters from local, county, and public health 
officials in a State disagreed with the doctoral degree requirement and 
cited the State Code that allows an individual with a baccalaureate or 
master's degree to direct a public health laboratory. The commenters 
noted that although the public health laboratories currently have a 
director who meets the CLIA regulations, many of these directors 
qualified under the former regulations at Sec.  493.1443(b)(5), the 
``grandfather'' provision that qualifies individuals if on or before 
February 28, 1992, they were qualified as a director under State law. 
Many of these directors will retire within 5 years.
    Response: For the reasons stated previously, we believe the 
education requirements for directors of high complexity laboratories 
are appropriate and should not be lowered. In addition, as noted by the 
commenters, the February 28, 1992 final rule with comment period 
included a grandfather provision that qualified individuals that were 
serving as laboratory directors under State law on or before that date. 
We also provided a phase-in provision, which allows individuals with 
doctoral degrees time to obtain board certification by the specified 
expiration date. The phase-in provision was extended on multiple 
occasions and during this 10-year period HHS has approved five 
additional boards. We believe sufficient time has been provided for 
individuals to become aware of the requirements. In this regard, the 
State revised its statutes in a February 18, 1998 amendment and now 
requires any city or county public health laboratory and its personnel 
to comply with the CLIA regulations.
    Comment: One commenter thought the proposed regulation would only 
allow physicians to serve as directors of laboratories performing high 
complexity testing.

[[Page 3673]]

    Response: Although physicians with certain training or experience 
are qualified to serve as directors of laboratories performing high 
complexity testing, the notice of proposed rulemaking only included 
proposed revisions to the qualification requirements by which an 
individual with a doctoral degree may serve as a director of a 
laboratory that performs high complexity testing.
    Comment: We received numerous comments on the qualification 
requirements for directors of laboratories performing 
histocompatibility testing. The majority of this group of commenters, 
which included the American Society of Histocompatibility and 
Immunogenetics (ASHI), and the American Board of Histocompatibility and 
Immunogenetics (ABHI), were in support of requiring specific 
histocompatibility training and experience for directors of 
laboratories performing histocompatibility testing. Specifically, they 
were in favor of requiring individuals with a doctoral degree to either 
meet the histocompatibility technical supervisor requirements specified 
in the former regulations at Sec.  493.1449(o) and be certified by 
ABHI; or be serving or have served as a director of a 
histocompatibility laboratory and meet the histocompatibility technical 
supervisor requirements at Sec.  493.1449(o). Opposing comments 
expressed concern that ASHI's proposal would exclude qualified 
individuals currently serving as directors of laboratories performing 
histocompatibility testing and is unnecessarily restrictive in an 
effort to protect the employment of those individuals who possess ABHI 
certification.
    Response: We do not agree that the qualifications for directors of 
laboratories performing histocompatibility testing, which is 
categorized as high complexity testing, need to be revised to include 
specific histocompatibility training and education requirements. We 
note the revisions suggested by ASHI would establish higher director 
qualification requirements for individuals having a doctoral degree 
than for physicians who direct laboratories performing 
histocompatibility testing. In addition, these suggested changes to the 
qualifications for directors of laboratories performing 
histocompatibility testing would be inconsistent with the former 
qualifications required to direct laboratories performing other testing 
specialties. Although the commenters maintained that histocompatibility 
is highly complex and requires specialized skills for direction, other 
specialty areas (for example, cytogenetics and pathology) are also 
complex and require specialized technical expertise. Under the CLIA 
regulations, the requirements for specialty training and experience are 
included under the qualification requirements for the technical 
supervisor, which vary depending on the specialty of service. The 
December 28, 2001 proposed regulation did not include technical 
supervisor requirements, and we are not making any changes to the 
former requirements for technical supervisors.
    In addition, several commenters mistakenly thought that having the 
director meet the histocompatibility technical supervisor requirements 
would eliminate the need for two individuals. Two individuals are only 
needed when a particular individual is unable to meet both the 
laboratory director and histocompatibility technical supervisor 
qualification requirements.
    Finally, while regulations specify the minimum requirements for 
compliance, accreditation organizations may establish higher 
requirements for laboratory accreditation.

Subpart P--Quality Assurance for Moderate Complexity (Including the 
Subcategory), High Complexity Testing, or Any Combination of These 
Tests

    Following publication of the February 28, 1992 final rule with 
comment period, we received approximately 25 comments in reference to 
subpart P. The comments were in response to the requirements for 
enforcement of a written quality assurance policy. The laboratory's 
policy was required to address the ongoing and overall monitoring and 
evaluation of the quality of the total testing process and the 
laboratory's policies and procedures, identifying and correcting 
problems to ensure the accurate, reliable, and prompt reporting of test 
results, and to ensure the adequacy and competency of the staff. Over 
half of the comments received agreed with most of the requirements. 
Approximately 25 percent of the comments disagreed with some of the 
requirements or offered specific revised language.
    Specific comments and responses regarding subpart P are set forth 
below.
    Comment: One commenter suggested that the CLIA regulation specify 
who has primary responsibility for QA activities by adding a statement, 
for example, ``The laboratory director is responsible for ensuring that 
a quality assurance program is established and maintained.''
    Response: We agree with the commenter. A requirement already 
appears at Sec. Sec.  493.1407(e)(5) and 493.1445(e)(5), moderate 
complexity and high complexity laboratory director responsibilities, 
respectively, and states ``The laboratory director must ensure that the 
quality control and quality assessment programs are established and 
maintained to ensure the quality of laboratory services provided and to 
identify failures in quality as they occur.'' In addition, we are now 
providing an introduction at Sec.  493.1200, subpart K that provides an 
overview of what quality systems include, the importance of ongoing 
assessment of these systems, and the laboratory's responsibility for 
establishment and maintenance of appropriate policies and procedures. 
The term ``quality assurance'' is synonymous with the term ``quality 
assessment.'' In addition, we are also making conforming changes 
(``assessment'' replaces ``assurance'') where appropriate.
    Comment: One commenter suggested adding text at Sec.  493.1709, 
Comparison of test results, that would acknowledge the role the 
manufacturer may have in verifying the accuracy and reliability of test 
results at least twice a year. Other commenters suggested language to 
clarify that tests not included under subpart I, performed by the 
laboratory at various (multiple) testing sites, must also be evaluated 
twice a year.
    Response: Manufacturers are not precluded from providing services 
to laboratories to assist in verification of the accuracy and 
reliability of test procedures. However, it is ultimately the 
responsibility of the laboratory to develop and implement protocols for 
the biannual evaluation and comparison of test results obtained using 
the different methodologies and instruments employed by the laboratory 
and various testing sites the laboratory may have (for example, central 
laboratory, satellite laboratories, point-of-care testing). In 
addition, the laboratory must, twice a year, verify the accuracy of any 
test it performs that is not listed in subpart I. Therefore, we believe 
the requirements, formerly at Sec.  493.1709 (now at Sec. Sec.  
493.1281 and 493.1236), clearly state the testing that must be 
evaluated and the requirements remain unchanged.
    Comment: We received a comment agreeing with the requirement at 
Sec.  493.1707, Proficiency testing assessment. The commenter stated 
that all proficiency testing (PT) results that were not correct should 
be investigated. Another commenter stated that all regulated analytes 
must be graded or the PT program must notify HHS and the

[[Page 3674]]

affected laboratory of any challenge, analyte, or test method for which 
it cannot produce a grade and the reasons why grading is not possible. 
A few commenters strongly disagreed with the practice of assigning a 
100 percent score to PT analytes when the laboratory has not earned the 
score. The commenters stated that this practice penalizes laboratories 
that have correctly performed testing on all PT samples and causes 
laboratories that receive false representation of a grade to believe 
their test performance is exemplary, when it has not been comparatively 
evaluated. Additionally, laboratory testing problems that exist are not 
identified; therefore, no corrective actions are taken.
    Response: Individual responses to the above comments are as 
follows:
    [sbull] We agree with the commenter and are retaining the 
requirement formerly at Sec.  493.1707 (now at Sec.  493.1236) for the 
laboratory to review and evaluate results obtained on proficiency 
testing. PT result review is part of the QA process.
    [sbull] We anticipate all regulated analytes (those listed in 
subpart I) will be graded by approved PT programs. The commenter is 
correct that, in some cases, not all challenges have been graded. 
Occasionally, as new methodologies or new instrumentation are developed 
for tests listed in subpart I, PT material is not always available or 
compatible with the new methods or instruments. In order to ensure that 
laboratories using new methodologies or instruments evaluate their 
performance, we are (now at Sec.  493.1236(c)(2)) requiring 
laboratories to verify twice annually the accuracy of tests listed in 
subpart I for which compatible PT material is not available from 
approved programs.
    [sbull] We agree with the commenter's recommendation to require PT 
programs to notify the laboratories and HHS of any challenge, analyte, 
or test method that cannot produce a grade and the reasons why grading 
is not possible. As CDC and CMS perform the annual review of PT 
programs required by the CLIA statute, programs must submit an annual 
report and, if needed, an interim report that identifies any previously 
unrecognized sources of variability in kits, instruments, methods, or 
PT samples that adversely affect the programs' ability to evaluate 
laboratory performance. This requires PT programs to report problems to 
CMS. We are also requiring programs to notify laboratories (on the 
laboratory's PT results report) of exceptions and/or problems that 
precluded an analyte from being graded.
    [sbull] We appreciate the commenters' concerns regarding false 
grading; however, there are reasons why false grading occurs. Almost 
all areas of testing under PT must be graded on an overall basis, that 
is, each analyte score under a subspecialty or specialty is averaged on 
each testing event to provide the laboratory with an overall 
subspecialty or overall specialty score. In order to determine an 
overall score, each analyte must receive a numerical score to allow the 
overall specialty or subspecialty to be graded. The circumstances that 
a PT program may assign an analyte score that does not reflect the 
laboratory's true test performance include: (1) Analyte evaluation does 
not produce at least 90 percent agreement among participant or referee 
laboratories that is required by regulation (the laboratory receives 
100 percent score); (2) laboratory did not participate in the testing 
event (the laboratory receives zero percent score); or (3) laboratory's 
PT results were received after the cut-off date for receipt (the 
laboratory receives a score of zero percent for the late return of 
results). In response to the commenters' concerns, we are now requiring 
at Sec.  493.1236(a)(2) that the laboratory verify the accuracy of the 
analytes for which a grade was assigned that did not reflect its true 
testing performance.

V. Provisions of the Final Rule

    In response to public comments on the final rule with comment 
period and to provide policy clarifications, we made a number of 
changes in this final rule, which are summarized as follows:

Subpart A--General Provisions (Definitions)

    [sbull] We added at Sec.  493.2 the definitions for the terms 
``calibration,'' ``calibration verification,'' ``FDA-cleared or 
approved test system,'' ``reportable range,'' and ``test system.''
    [sbull] We revised Sec.  493.3(b)(3) to remove the words ``National 
Institutes on Drug Abuse (NIDA)'' and add, in their place, the agency's 
new name, ``Substance Abuse and Mental Health Services Administration 
(SAMHSA).''
    [sbull] We revised Sec.  493.20 by removing the reference to 
``subpart P'' and adding the cross reference to ``Sec.  493.1773.''
    [sbull] We revised Sec.  493.25 by removing the reference to 
``subpart P'' and adding the cross reference to ``Sec.  493.1773.''

Subpart C--Registration Certificate, Certificate for Provider-performed 
Microscopy Procedures, and Certificate of Compliance

    [sbull] We revised Sec.  493.43(a) by removing the words ``tests of 
moderate complexity (including the subcategory) or high complexity, or 
any combination of these tests,'' and adding, in their place, the words 
``nonwaived testing.''
    [sbull] We revised Sec.  493.45 by removing the reference to 
``subpart P.''
    [sbull] We revised Sec.  493.47 by removing the reference to 
``subpart P''.
    [sbull] We revised Sec.  493.47(c)(3) by removing the cross 
reference to ``Sec.  493.1776'' and adding, in its place, a cross 
reference to ``Sec. Sec.  493.1773'' and ``493.1775.''
    [sbull] We revised Sec.  493.49 by removing the reference to 
``subpart P.''

Subpart F--General Administration

    [sbull] We added at Sec.  493.643(c)(3)(ix) the word ``Clinical 
before the word ``Cytogenetics'' to correct a technical error. The word 
was inadvertently omitted from the final rule with comment period.

Subpart H--Participation In Proficiency Testing for Laboratories 
Performing Nonwaived Testing

    [sbull] We revised the heading of subpart H to read ``Participation 
In Proficiency Testing for Laboratories Performing Nonwaived Testing.''
    [sbull] We revised ``Sec.  493.801(a)(2)(ii)'' by removing the 
cross reference to ``Sec.  493.1709'' and adding, in its place, ``Sec.  
493.1236(c)(1).''
    [sbull] We revised ``Sec.  493.803(a)'' by removing the words 
``tests of moderate complexity (including the subcategory), and/or high 
complexity'' and adding, in their place, the words ``nonwaived 
testing.''
    [sbull] We revised the heading of Sec.  493.807 to read 
``Condition: Reinstatement of laboratories performing nonwaived 
testing.''

Subpart I--Proficiency Testing Programs for Nonwaived Testing

    [sbull] We revised the heading of subpart I to read ``Proficiency 
Testing Programs for Nonwaived Testing.''
    [sbull] We revised this subpart by changing the 90 percent 
consensus requirement to 80 percent consensus.
    [sbull] We revised Sec.  493.945 by removing the cross reference to 
``Sec.  493.1257'' and adding in its place Sec. Sec.  
493.1105(a)(7)(i)(A) and 493.1274(f)(2).''

Revisions to Subpart J and K

    As stated in section II of this preamble (Highlights and 
Organization of Final Rule), we have consolidated and reorganized the 
requirements formerly in Subpart J--Patient Test Management for 
Moderate Complexity (Including the Subcategory), High Complexity, or 
Any Combination of These Tests, Subpart K--Quality Control for Tests of 
Moderate Complexity (Including the

[[Page 3675]]

Subcategory), High Complexity, or Any Combination of These Tests, and 
Subpart P--Quality Assurance for Moderate Complexity (Including the 
Subcategory) or High Complexity Testing, or Any Combination of These 
Tests, into a new Subpart J--Facility Administration for Nonwaived 
Testing, and Subpart K--Quality Systems for Nonwaived Testing. Below, 
we have only set forth substantive revisions to subparts J and K.

Subpart J--Facility Administration for Nonwaived Testing

    [sbull] We revised the heading of subpart J to read Facility 
Administration for Nonwaived Testing.
    [sbull] We revised subpart J to consist of Sec. Sec.  493.1100 
through 493.1105.
    [sbull] We specified now at Sec.  493.1100 that laboratories 
performing nonwaived testing must meet the applicable standard level 
requirements in Sec. Sec.  493.1101 through 493.1105.
    [sbull] We added the requirement now at Sec.  493.1101(c) that 
laboratories must comply with Federal, State, and local requirements 
concerning laboratories and ensure that adequate safety precautions are 
in place to provide protection from laboratory hazards.
    [sbull] We revised the language now at Sec.  493.1101(d) (formerly 
at Sec.  493.1204(b)) requiring safety procedures to be accessible 
rather than posted.
    [sbull] We clarified the record keeping requirements now at Sec.  
493.1101(e) for laboratories to store and maintain records in a manner 
that ensures proper preservation. This clarification applies to the 
requirements now at Sec.  493.1771(c) and (d), and former Sec. Sec.  
493.1105, 493.1107, and 493.1221 introductory text.
    [sbull] We removed the language formerly at Sec.  493.1103(c) 
regarding laboratories providing oral instruction to patients as a 
supplement to written instructions, when appropriate.
    [sbull] We clarified the requirement now at Sec.  493.1103(d) 
(formerly at Sec.  493.1271) that the facility must report transfusion 
reactions to the laboratories and, as appropriate, to Federal and State 
authorities.
    [sbull] We revised the language now at Sec.  493.1105(a)(3)(i) 
(formerly at Sec.  493.1221) to specify that the laboratory must retain 
records of test system performance specifications that the laboratory 
establishes or verifies under Sec.  493.1253 for the period of time the 
laboratory uses the test system but no less than 2 years.
    [sbull] We revised the language now at Sec.  493.1105(a)(3)(ii) 
(formerly Sec.  493.1107 introductory text) and Sec.  493.1105(a)(6)(i) 
(formerly Sec.  493.1109 introductory text) to specify the record 
retention requirements for immunohematology and blood and blood 
products to ensure consistency with the FDA requirements.
    [sbull] We revised the requirement now at Sec.  493.1105(a)(6) 
(formerly Sec.  493.1109 introductory text) to remove the words ``exact 
duplicate'' and specify that the laboratory must be able to retrieve a 
copy of the original report.

Subpart K--Quality Systems for Nonwaived Testing

    [sbull] We revised the heading of subpart K to read ``Quality 
Systems for Nonwaived Testing.''
    [sbull] We revised subpart K to consist of Sec. Sec.  493.1200 
through 493.1299.
    [sbull] We revised the introductory text now at Sec.  493.1200 to 
provide an overview of quality systems, including the importance of 
ongoing assessment of these systems, and the laboratory's 
responsibility for establishment and maintenance of appropriate 
policies and procedures.
    [sbull] We removed the lead-in paragraph formerly at Sec.  
493.1201(a) explaining the division between general QC and the QC for 
the specialties and subspecialties.
    [sbull] We removed the requirement formerly at Sec.  493.1201(a)(1) 
regarding the clearance process for alternative QC procedures that were 
never established by the FDA.
    [sbull] We removed the requirement formerly at Sec.  493.1203 
regarding the clearance process for moderate complexity testing.
    [sbull] We redesignated the requirement formerly at Sec.  493.1205 
regarding test methods, equipment, instrumentation, reagents, 
materials, and supplies. We incorporated the majority of these 
provisions into Sec.  493.1252. The requirements formerly at Sec.  
493.1205(b) are now at Sec.  493.1101(b) and the biologic product 
dating requirements formerly at Sec.  493.1205(e) are now at Sec.  
493.1271(b).
    [sbull] We removed the requirement formerly at Sec.  493.1213(b)(1) 
regarding the QC clearance process for the manufacturer's process for 
verification of performance specifications for new patient testing 
devices introduced by the laboratory.
    [sbull] We removed the requirement formerly at Sec.  493.1215(a)(1) 
regarding the CLIA QC clearance process for maintenance of equipment, 
instruments, and test systems.
    [sbull] We removed the requirement formerly at Sec.  493.1217(a) 
regarding the CLIA QC clearance process for use of the manufacturer's 
instructions for calibration and calibration verification procedures.
    [sbull] We removed the requirement formerly at Sec.  
493.1217(b)(2)(ii)(B)(1) (calibration verification requirement) 
regarding use of calibration materials traceable to a reference method 
or reference material of known value to allow flexibility in choosing 
material for calibration verification.
    [sbull] We removed the requirements formerly at Sec.  493.1225, the 
Condition of Microbiology, as it is a duplicate of the requirements 
under the Conditions of Bacteriology, Mycobacteriology, Mycology, 
Parasitology, and Virology, now at Sec. Sec.  493.1201, 493.1202, 
493.1203, 493.1204, and 493.1205, respectively.
    [sbull] We clarified the requirement now at Sec.  493.1236 
(formerly at Sec.  493.1707) that laboratories must verify the accuracy 
of any analyte, specialty, or subspecialty when it is assigned a 
proficiency testing score that does not reflect laboratory test 
performance.
    [sbull] We added the requirement now at Sec.  493.1236(c)(2) that 
laboratories verify twice annually the accuracy of tests listed in 
subpart I for which compatible PT material is not available from 
approved PT programs.
    [sbull] We removed the requirement formerly at Sec.  493.1237, the 
Condition of Diagnostic Immunology, as it is a duplicate of the 
requirements under the Conditions of Syphilis Serology and General 
Immunology now at Sec. Sec.  493.1207 and 493.1208, respectively.
    [sbull] We revised the language now at Sec.  493.1241(b) (formerly 
at Sec.  493.1105) to clarify that an oral request for laboratory tests 
is permitted only if laboratory requests written or electronic 
authorization for testing within 30 days of the oral request and 
documents the efforts made to obtain a written or electronic 
authorization.
    [sbull] We revised the language now at Sec.  493.1241(c)(3) 
(formerly at Sec.  493.1105(e) and (f)) to specify that the test 
requisition must solicit the patient's sex and age or date of birth.
    [sbull] We added the requirement now at Sec.  493.1241(c)(5) 
(formerly Sec.  493.1105(f)) that the laboratory must ensure that the 
test requisition solicits the source of the specimen when appropriate.
    [sbull] We revised the language now at Sec.  493.1241(c)(7) 
(formerly at Sec.  493.1105(e)) removing the age or date of birth 
requirement for Pap smear requisitions because it is now a requirement 
for all test requisitions at Sec.  493.1241(c)(3).
    [sbull] We revised the requirement now at Sec.  493.1241(e) 
(formerly Sec.  493.1701) to provide clarification that if the 
laboratory transcribes or enters test requisition or authorization 
information into a record system or laboratory information system, the 
laboratory must

[[Page 3676]]

ensure that the information is transcribed or entered accurately.
    [sbull] We revised the requirement now at Sec.  493.1242(a)(3) 
(formerly Sec.  493.1105(f)) clarifying that the specimen source 
requirement, when appropriate, is part of the laboratory's submission, 
handling, and referral procedures.
    [sbull] We removed the requirement formerly at Sec.  493.1243, the 
Condition of Chemistry, as it is a duplicate requirement under the 
Conditions of Routine Chemistry at Sec.  493.1210, Urinalysis at Sec.  
493.1211, Endocrinology at Sec.  493.1212, and Toxicology at Sec.  
493.1213.
    [sbull] We clarified the requirement now at Sec.  493.1251(b)(13) 
(formerly at Sec.  493.1211(b)(14)) that the procedure manual must 
include in the test procedure the laboratory's system for entering 
results in the patient record and reporting patient results including 
the protocol for reporting panic or alert values, when appropriate.
    [sbull] We revised the language now at Sec.  493.1251(d) (formerly 
at Sec.  493.1211(d)) to provide that procedures and changes in 
procedures must be approved, signed, and dated by the current 
laboratory director before use.
    [sbull] We revised the language now at Sec.  493.1252(b) (formerly 
Sec. Sec.  493.1202(c)(1) and 493.1205(c)) to specify that the 
laboratory's criteria for storage of reagents and specimens and test 
system operations must be consistent with the manufacturer's 
instructions, when available.
    [sbull] We revised the language now at Sec.  493.1253(a) (formerly 
at Sec.  493.1213(a)) to provide that laboratories are not required to 
verify or establish performance specifications for any test system used 
by the laboratory before April 24, 2003.
    [sbull] We revised the language now at Sec.  493.1253(b)(1) 
(formerly at Sec.  493.1213(b)(2)) by adding the words ``FDA-cleared or 
approved test system'' to the requirements regarding verification of 
performance specifications.
    [sbull] We revised the heading now at Sec.  493.1254 (formerly 
Sec.  493.1215) to read ``Maintenance and function checks.''
    [sbull] We revised the language now at Sec.  493.1254(a)(2) 
(formerly at Sec.  493.1215(b)(2)(ii)) regarding function checks by 
removing the word ``laboratory'' and adding, in its place, the word 
``manufacturers.''
    [sbull] We clarified the requirement now at Sec.  493.1254(a)(2) 
(formerly at Sec. Sec.  493.1202(c)(1) and 493.1215(b)(2)(ii)) to 
require that function checks be within the manufacturer's established 
limits before conducting patient testing.
    [sbull] We removed the requirement formerly at Sec.  493.1255, the 
Condition of Pathology, as it is a duplicate requirement under the 
Conditions of Histopathology, Oral Pathology and Cytology now at 
Sec. Sec.  493.1219, 493.1220, and 493.1221, respectively.
    [sbull] We revised the language now at Sec.  493.1256 by removing 
the mandatory concurrent control testing requirements formerly at 
Sec. Sec.  493.1237 Diagnostic immunology; 493.1239 Syphilis serology; 
and 493.1241 General immunology. We now require two levels of QC 
materials once each day of testing.
    [sbull] We revised the language now at Sec.  493.1256(d) (formerly 
at Sec.  493.1218(b)) reducing the requirement by removing the 
specialty-specific control requirements (formerly at Sec.  493.1253(b)) 
for automated hematology analyzers. We now require two levels of 
control materials once each day of testing.
    [sbull] We revised the language now at Sec.  493.1256(d)(3) 
(formerly at Sec.  493.1218(b)) to clarify that QC materials are 
assayed or examined each day of patient testing.
    [sbull] We revised the requirement now at Sec.  493.1256(d)(3) for 
hematology by reducing the required frequency for control testing 
(formerly at Sec.  493.1253(b)) from once each 8 hours of operation to 
once each day of testing.
    [sbull] We added the requirement now at Sec.  493.1256(d)(3)(v) 
that the laboratory must use a control system capable of detecting 
reaction inhibition when performing molecular amplification procedures 
in which inhibition is a significant source of false negative results.
    [sbull] We removed the term ``drug abuse screening'' at Sec.  
493.1256(d)(4)(i), and added the term ``all known substances or drug 
groups'' identified and reported by the laboratory to accommodate the 
wider use of the technology.
    [sbull] We revised the language now at Sec.  493.1256(d)(5) 
(formerly at Sec.  493.1218(b)(3)) to clarify that the laboratory must 
for each electrophoretic procedure, include, concurrent with patient 
specimens, at least one control material containing the substances 
being identified or measured.
    [sbull] We revised the language now at Sec.  493.1256(e)(2) 
(formerly Sec.  493.1218(f)(2)) to clarify the use of staining 
materials.
    [sbull] We clarified the use of calibration materials now at Sec.  
493.1256(d)(9) (formerly at Sec.  493.1218(h)(2)) to provide that 
calibration material used as a control material must be from a 
different lot number than that used to establish a cut-off value or to 
calibrate the test system.
    [sbull] We revised the requirement now at Sec.  493.1261 by 
incorporating the bacteriology requirements formerly at Sec.  493.1227.
    [sbull] We revised the language now at Sec.  493.1261 (formerly 
Sec.  493.1227), reducing the requirements by removing the reference to 
specific control requirements in the subspecialty of bacteriology.
    [sbull] We revised the requirement now at Sec.  493.1262 by 
incorporating the mycobacteriology requirements formerly at Sec.  
493.1229.
    [sbull] We added a requirement in mycobacteriology now at Sec.  
493.1262(a) (formerly Sec.  493.1229(a)) for an acid fast control 
organism that produces a negative reaction.
    [sbull] We revised the requirement now at Sec.  493.1263 by 
incorporating the mycology requirements formerly at Sec.  493.1231.
    [sbull] We revised the requirement now at Sec.  493.1263(a) 
(formerly at Sec.  493.1218(f)(2)). We reduced the requirement to QC 
certain staining materials each day of use to only checking each batch, 
lot number, and shipment of lactophenol cotton blue when prepared or 
opened for intended reactivity.
    [sbull] We revised the requirement now at Sec.  493.1263(b) 
(formerly Sec.  493.1213(d)) by reducing the requirement for daily 
testing to merely testing each batch of media and each lot number and 
shipment of antifungal agents before or concurrent with initial use.
    [sbull] We revised the requirement now at Sec.  493.1264 by 
incorporating the parasitology requirements formerly at Sec.  493.1233.
    [sbull] We revised the requirement now at Sec.  493.1265 by 
incorporating the virology requirements formerly at Sec.  493.1235.
    [sbull] We removed the requirement formerly at Sec.  
493.1265(a)(10) that required the laboratory to use specific techniques 
such as mixed lymphocyte cultures to determine HLA Class II 
incompatibilities.
    [sbull] We removed the requirement formerly at Sec.  
493.1265(a)(13) that required histocompatibility testing personnel to 
evaluate unknowns on a monthly basis because it is duplicative of the 
laboratory director responsibilities at Sec.  493.1445(e).
    [sbull] We revised the requirement now at Sec.  493.1267 by 
incorporating the routine chemistry requirements formerly at Sec.  
493.1245.
    [sbull] We revised the language now at Sec.  493.1267(b) (formerly 
at Sec. Sec.  493.1245(c) and (d)) by removing reference to the words 
``calibration and calibration material'' from the blood gas 
requirements. However, we allow

[[Page 3677]]

calibration material as a control material provided it is from a 
different lot number than that used to calibrate the test system or 
establish a cut-off.
    [sbull] We revised the requirements now at Sec.  493.1269 by 
incorporating the hematology requirements formerly at Sec.  493.1253.
    [sbull] We revised the requirement now at Sec.  493.1271 by 
incorporating the immunohematology requirements formerly at Sec. Sec.  
493.1239(e), 493.1241(d), 493.1269, 493.1273, 493.1275, 493.1283, and 
493.1285.
    [sbull] We revised the requirement now at Sec. Sec.  493.1271(a)(1) 
and (b) (formerly Sec. Sec.  493.1269(a) and 493.1273) to cite the 
specific 21 CFR requirements that must be met under the CLIA 
regulations.
    [sbull] We revised the requirement now at Sec.  493.1273 by 
incorporating the histopathology requirements formerly at Sec.  
493.1259.
    [sbull] We added a requirement at Sec.  493.1273(a) (formerly at 
Sec.  493.1259) that the laboratory must check immunohistochemical 
stains for positive and negative reactivity each time of use in order 
to be consistent with the general QC requirements at Sec.  
493.1256(e)(3).
    [sbull] We revised the language now at Sec.  493.1273(c) (formerly 
at Sec.  493.1259(b)) to add that an individual who has successfully 
completed a training program in neuromuscular pathology approved by HHS 
may examine and provide reports for neuromuscular pathology.
    [sbull] We revised the requirement now at Sec.  493.1274 by 
incorporating the cytology requirements formerly at Sec.  493.1257.
    [sbull] We revised the language now at Sec.  493.1274(d)(2)(iii) 
(formerly at Sec.  493.1257(b)(2)) by removing the reference to 
gynecologic slides from the 200-workload limit that applies only to 
nongynecologic slides.
    [sbull] We revised the language now at Sec.  493.1274(e)(1) 
(formerly at 493.1257(c)(1)) by removing the requirement that a 
technical supervisor review cases categorized as reactive and 
reparative changes.
    [sbull] We revised the requirement now at Sec.  493.1276 (formerly 
at Sec.  493.1267) by incorporating the clinical cytogenetics 
requirements.
    [sbull] We clarified the requirement at Sec.  493.1276(a) (formerly 
Sec. Sec.  493.1107 and 493.1267(c)) by specifying that the laboratory 
must have policies and procedures for ensuring accurate and reliable 
patient specimen identification for karyotypes.
    [sbull] We revised the requirement now at Sec.  493.1276(b)(2) 
(formerly at Sec.  493.1267(b)) to specify that the laboratory must 
have records that document that the resolution used was appropriate for 
the type of tissue or specimen, and the type of study required based on 
the clinical information provided to the laboratory.
    [sbull] We revised the language now at Sec.  493.1276(c) (formerly 
at Sec.  493.1267(a)) by removing the requirements pertaining to the 
performance of X and Y chromatin counts for sex determination and 
requiring full chromosome analysis for sex determination.
    [sbull] We revised the language now at Sec.  493.1276(d) (formerly 
at Sec.  493.1267(d)) by removing the reference to the words 
``appropriate nomenclature'' and specifying that the laboratory report 
must use the International System of Cytogenetic Nomenclature.
    [sbull] We revised the requirement now at Sec.  493.1278 by 
incorporating the histocompatibilty requirements formerly at Sec.  
493.1265.
    [sbull] We added the requirement now at Sec.  493.1278(a)(3) that 
reagent specificity is required when reagent typing sera inventory is 
prepared in-house.
    [sbull] We added requirements now at Sec.  493.1278(b)(1) that the 
laboratory must use a technique that is established to optimally 
define, as applicable, HLA Class I and II specificity.
    [sbull] We added requirements at Sec.  493.1278(d)(1) and (d)(2) to 
specify that the laboratory must use a technique that detects HLA 
specific antibody with a specificity equivalent or superior to that of 
the basic complement-dependent microlymphocytotoxicity assay, and use a 
method that distinguishes antibodies to HLA class II antigens from 
antibodies to Class I antigens.
    [sbull] We revised the language now at Sec.  493.1278(d)(4) and 
(d)(5) (formerly at 493.1265(a)(2)(ii) and (a)(8)(i)) to require 
laboratories to make a reasonable attempt to have available monthly 
serum specimens for periodic antibody screening and crossmatch, and 
have available and follow a written policy consistent with clinical 
transplant protocols for the frequency of performing antibody 
screening.
    [sbull] We added the requirement now at Sec.  493.1278(d)(7) to 
specify that for antibody screening, the laboratory must, as 
applicable, have available, and follow criteria and procedures for 
antibody identification to the level appropriate to support clinical 
transplant protocol.
    [sbull] We revised the language now at Sec.  493.1278(e)(1) 
(formerly Sec.  493.1265(a)(1)(ii) to clarify that the techniques for 
crossmatching must be documented to have increased sensitivity in 
comparison to the basic complement-dependent microlymphocytoxicity 
assay.
    [sbull] We revised the requirement now at Sec.  493.1278(f)(1) 
(formerly at Sec.  493.1265(b) and (c)) that requires specific testing 
protocols to be less prescriptive and allow laboratories to define 
testing policies and protocols for each type of cell, tissue, or organ 
to be transfused or transplanted.
    [sbull] We clarified the requirement now at Sec.  493.1278(f)(3) 
(formerly at Sec.  493.1265(b)(3)) that the laboratory must have 
available, and follow, policies that address when HLA testing and final 
crossmatches are required for presensitized non-renal transplant 
recipients.
    [sbull] We clarified the requirements now at Sec.  493.1291(a) 
(formerly at Sec.  493.1109(a)) to provide that the laboratory must 
have adequate systems in place to ensure test results and other patient 
specific data are accurately and reliably transmitted from the point of 
data entry (whether interfaced or entered manually) to final report 
destination, in a timely manner.
    [sbull] We clarified the requirement at Sec.  493.1291(c)(3) 
(formerly at Sec. Sec.  493.1109 and 493.1109(a)) to specify that the 
date of the test report must be identified on the report.
    [sbull] We clarified the requirement now at Sec.  493.1291(c)(5) 
(formerly at Sec.  493.1109) to indicate that the test report must 
include the specimen source, if applicable.
    [sbull] We added language relevant to interpretation to the test 
report requirements now at Sec.  493.1291(c)(6) (formerly Sec.  
493.1109(b)) for those test results that require supplemental 
information.
    [sbull] We revised the language now at Sec.  493.1291(j) (formerly 
Sec.  493.1109(h)) by removing the words ``exact duplicate'' and 
clarified the language by specifying that all test reports or records 
of the information on the test reports must be maintained by the 
laboratory in a manner that permits ready identification and timely 
accessibility.

Subpart M--Personnel for Nonwaived Testing

    [sbull] We revised the heading of subpart M to read ``Personnel for 
Nonwaived Testing'' to conform with the names of the new subparts J and 
K.
    [sbull] We revised Sec.  493.1359(a)(3) by removing the reference 
to ``subpart P.''
    [sbull] We revised Sec.  493.1407(e)(5) by removing the word 
``assurance'' and, adding in its place, the word ``assessment.''
    [sbull] We revised Sec.  493.1443(b)(3) to allow individuals with a 
doctoral degree who are serving or have served as directors of 
laboratories performing high complexity testing before February 24,

[[Page 3678]]

2003, under the phase-in provision, to continue to qualify as directors 
of laboratories performing high complexity testing.
    [sbull] We revised the requirement at Sec.  493.1443(b)(3)(i) by 
removing the list of HHS-approved boards. We are placing the list in 
Appendix C of the State Operation Manual (CMS Pub. 7) to allow more 
timely updates.
    [sbull] We revised Sec.  493.1445(e)(5) to refer to the quality 
assessment program.
    [sbull] We revised Sec.  493.1451(c)(4) by removing the reference 
to Sec.  493.1257(c) and adding, in its place Sec.  493.1274(d) and 
(e).
    [sbull] We revised Sec.  493.1471(b)(2) and Sec.  493.1485(a) by 
removing ``Sec.  493.1257(d),'' and adding, in its place, ``Sec.  
493.1274(c).''

Removal of Subpart P

    As stated in section II of this preamble (Highlights and 
Organization of Final Rule), we incorporated the former ``Subpart P--
Quality Assurance; Moderate Complexity (Including the Subcategory) or 
High Complexity Testing, or Any Combination of These Tests'' under the 
appropriate sections now located in Subpart K, General Laboratory 
Systems, Preanalytic Systems, Analytic Systems, and Postanalytic 
Systems.

Subpart R--Enforcement Procedures

    [sbull] We revised Sec.  493.1844 by removing the reference to 
``subpart P.''

Subpart T--Consultations

    [sbull] We revised Sec.  493.2001(e)(1) to read ``Criteria for 
categorizing nonwaived testing.''
    [sbull] We revised Sec.  493.2001(e)(4) to read ``Facility 
administration and quality systems standards;''

VI. Collection of Information Requirements

    Under the Paperwork Reduction Act (PRA) of 1995, we are required to 
provide 60-day notice in the Federal Register and solicit public 
comment before a collection of information is submitted to the Office 
of Management and Budget (OMB) for review and approval. In order to 
fairly evaluate whether an information collection should be approved by 
OMB, section 3506(c)(2)(A) of the PRA requires that we solicit comment 
on the following issues:
    [sbull] The need for the information collection and its usefulness 
in carrying out the proper functions of our agency.
    [sbull] The accuracy of our estimate of the information collection 
burden.
    [sbull] The quality, utility, and clarity of the information to be 
collected.
    [sbull] Recommendations to minimize the information collection 
burden on the affected public, including automated collection 
techniques.
    We are soliciting public comment on each of these issues for the 
sections that contain new information collection requirements. Except 
as indicated below, all of the information collection burden in this 
final rule has been approved by the OMB under approval number 0938-0612 
through June 2004.
    Because the sections in this final rule are a reorganization of 
former sections, the burden approval numbers cited state the best 
approximation we could make for which combinations of former burden 
numbers match with the sections as specified in this final rule. Our 
approximations are as follows:
Section 493.1105 Standard: Retention Requirements
    Under paragraph (a)(6), Test reports, the laboratory must retain or 
be able to retrieve a copy of the original report (including final, 
preliminary, and corrected reports) at least 2 years after the date of 
reporting.
    The change in this paragraph is that now the laboratory has the 
option of either retaining a copy of the report or having the 
capability of generating a copy of the report. This revision does not 
change the burden captured under OMB approval number 0938-0612.
Section 493.1241 Standard: Test Request
    At paragraph (c), the laboratory must ensure that the written or 
electronic test requisition solicits the following:
    [sbull] The sex and age or date of birth of the patient.
    [sbull] The source of the specimen, as appropriate.
    [sbull] The date and, if appropriate, time of specimen collection.
    [sbull] Any additional information relevant and necessary to a 
specific test to ensure accurate and timely testing, and reporting of 
results, including interpretation, if applicable.
    These new requirements mandate that laboratories solicit the sex 
and age or date of birth of the patient and, if appropriate, the source 
of the specimen and the time of specimen collection on the test 
request. In addition, the requirements clarify that the relevant 
information needed to ensure accurate and timely testing and reporting 
of results includes relevant information for interpretation of results.
    We believe the burden of soliciting this information is minimal, as 
it is routinely captured by laboratories as part of good business 
practices. Therefore, while this information collection requirement is 
subject to the PRA, we believe the burden is exempt as defined in 5 CFR 
1320.3(b)(2) because the time, effort, and financial resources 
necessary to comply with the requirement are incurred by persons in the 
normal course of their activities.
Section 493.1242 Standard: Specimen Submission, Handling, and Referral
    At paragraph (a), we are clarifying the requirement, formerly at 
Sec.  493.1103(a), that the laboratory's written policies and 
procedures for specimen labeling specify that the patient's name or 
unique patient identifier, and when appropriate, specimen source be on 
the specimen label. This revision does not add additional reporting 
burden for this requirement under OMB approval number 0938-0612.
Section 493.1251 Standard: Procedure Manual
    Paragraph (b)(13) requires that the procedure manual include the 
laboratory's system for entering results in the patient record and 
reporting patient results including, when appropriate, the protocol for 
reporting ``panic or alert values.''
    This requirement, formerly at Sec.  493.1211(b)(14), now includes 
the provision for a written procedure describing the laboratory's 
processes for entering results into patient records. This revision does 
not change the paperwork burden captured for this requirement under OMB 
approval number 0938-0612.
Section 493.1253 Standard: Establishment and Verification of 
Performance Specifications
    Each laboratory that introduces an unmodified, FDA-cleared or 
approved test system must, before reporting patient test results, 
demonstrate that it can obtain performance specifications comparable to 
those established by the manufacturer for the specified performance 
characteristics.
    In addition, each laboratory that uses a test system in which 
performance specifications are not provided by the manufacturer, 
modifies an FDA-cleared or approved test system or introduces a test 
system not subject to FDA clearance or approval (includes standardized 
methods and methods developed in-house) must, before reporting patient 
test results, establish for each test system the performance 
specifications for specified performance characteristics.
    Based upon the performance specifications verified or established, 
the laboratory must determine calibration procedures and control

[[Page 3679]]

procedures. Also, the laboratory must have documentation of the 
laboratory's performance of all activities specified in this section.
    This is a 2-part requirement and will affect laboratories 
differently depending on whether they are verifying or establishing 
performance specifications for a test method. In addition, it only 
applies to new laboratories and new tests instituted in existing 
laboratories on and after April 24, 2003. Therefore, the number of 
laboratories needing to meet this requirement will be minimal. While 
this is a new requirement for some laboratories performing testing 
using unmodified, moderate complexity test systems approved or cleared 
by the FDA, it only applies to tests newly introduced into existing 
laboratories and to all tests in laboratories first established on or 
after April 24, 2003. In addition, it is common practice for test 
system manufacturers to perform or provide extensive assistance with 
this quality control activity when a laboratory buys or leases an 
instrument or other new test system. Thus, in practice, most of the 
burden for recording and documenting the quality control requirements 
are already born by the test system manufacturers. We do not believe 
that this burden will be shifted to the laboratory. Also, accrediting 
organizations and States with licensure programs, after which the CLIA 
requirements were modeled, have traditionally required laboratories to 
perform these activities. Therefore, while this information collection 
requirement is subject to the PRA, the burden is exempt as defined in 5 
CFR 1320.3(b)(2) because the time, effort, and financial resources 
necessary to comply with the requirement are incurred by persons in the 
normal course of their activities.
Section 493.1256 Control Procedures
    These requirements were previously at Sec.  493.1218 and approved 
under OMB approval number 0938-0612. The burden associated with these 
requirements involves the documentation of the control results and 
corrective action taken when control results do not meet the 
laboratory's acceptability criteria. Therefore, we are revising the 
paperwork requirements to some extent.
    Under paragraph (d), the laboratory must do the following, as 
applicable:
    [sbull] In paragraphs (d)(3)(i) and (ii), for each quantitative and 
qualitative procedure, include two control materials of different 
concentrations and a positive and negative control material, 
respectively.
    There may be increased reporting for unmodified moderate complexity 
tests (formerly at Sec.  493.1202(c)) whose manufacturer's instructions 
did not include these requirements. The burden for the remainder of the 
tests is captured for this requirement under OMB approval number 0938-
0612.
    [sbull] In paragraph (d)(3)(iii), for each semiquantitative 
procedure, include a negative control material and, as applicable, a 
control material with graded or titered reactivity.
    There will be an increase in paperwork burden for unmodified 
moderate complexity tests (formerly at Sec.  493.1202(c)) whose 
manufacturer's instructions did not include this requirement and for 
tests not subject to the specialty requirements formerly at Sec. Sec.  
493.1239(b) or 493.1241(a). The burden for the remainder of these tests 
for this requirement is captured under OMB approval number 0938-0612.
    [sbull] In paragraph (d)(3)(v), for each molecular amplification 
procedure, include two control materials and, if reaction inhibition is 
a significant source of false negative results, a control material 
capable of detecting inhibition.
    There will be increased burden for recording the additional control 
results, when needed. The burden of recording the former control 
results is captured for this requirement under OMB approval number 
0938-0612.
    [sbull] In paragraph (d)(6), when a complete change of reagents is 
introduced, major preventive maintenance is performed, or any critical 
part that may influence test performance is replaced, the laboratory 
must, before resuming patient testing perform control material testing 
as specified under paragraph (d) of this section.
    There will be an increase in burden for tests whose manufacturer's 
instructions did not include the requirements for control material 
testing specified under paragraph (d) of this section. The burden for 
the remainder of the tests is captured for this requirement under OMB 
approval number 0938-0612.
    [sbull] Under paragraph (d)(10)(iii), when control materials 
providing quantitative results are used, statistical parameters for 
unassayed materials must be established over time by the laboratory 
through concurrent testing of control materials having previously 
determined statistical parameters.
    There will be an increase in reporting for moderate complexity 
tests formerly subject to the phase-in at Sec.  493.1202(c). The burden 
for the remainder of these tests is captured under OMB approval number 
0938-0612.
    In paragraph (e)(3), the laboratory must check fluorescent and 
immunohistochemical stains for positive and negative reactivity each 
time of use. Therefore, reporting will increase from one to two control 
results in the subspecialty of histopathology for tests performed using 
immunohistochemical stains. For mycobacteriology, recording control 
results will increase from each week of use to each time of use for 
fluorochrome acid-fast stains. The burden of reporting one control 
result is captured for these requirements under OMB approval number 
0938-0612.
    Under the former OMB approval, we allotted 5 minutes per day for 
the reporting requirements in the former Sec.  493.1218. This time 
allotment was based on the assumption that most of the previously 
unregulated laboratories were performing moderate complexity testing 
and ran a total of four QC samples daily. This time allotted included 
reporting for the burden associated with all the specialties and 
subspecialties; therefore, we believe the burden was slightly 
underestimated.
    We are allotting 5 minutes per day to perform this documentation 
for the specialties and subspecialties (except bacteriology, 
mycobacteriology, hematology, and histopathology) and are adjusting 
this burden to reflect the number of laboratories currently affected by 
this rule. We are addressing the specialties and subspecialties of 
bacteriology, mycobacteriology, hematology, and histopathology 
separately. We are assuming laboratories are documenting control 
activities on an average of 6 days per week. Therefore, the burden for 
the specialties and subspecialties (except bacteriology, 
mycobacteriology, hematology and histopathology) can be calculated as 5 
min./day x 24 days/month = 120 min./month = 2 hrs./month 2 hrs./month x 
12 months/yr. = 24 hours/laboratory/yr.
    The total estimated burden for this requirement (now at Sec.  
493.1256) is 27,685 laboratories (total number of laboratories minus 
the number of waived laboratories, provider performed microscopy (PPM) 
laboratories, and previously regulated laboratories) x 24 hrs./yr. = 
664,440 hrs./yr.
Section 493.1261 Standard: Bacteriology
    For the subspecialty of bacteriology, in this final rule at 
paragraph (a), the laboratory must check the following for positive and 
negative reactivity using control organisms:
    [sbull] Each day of use for beta-lactamase methods other than 
Cefinase TM.
    [sbull] Each week of use for Gram stains.

[[Page 3680]]

    [sbull] When each batch (prepared in-house), lot number 
(commercially prepared), and shipment of antisera is prepared or opened 
and once every 6 months thereafter.
    In paragraph (b), for antimicrobial susceptibility tests, the 
laboratory must check each batch of media, lot number, and shipment of 
antimicrobial agent(s) before, or concurrent with, initial use, using 
approved reference organisms and, each day tests are performed, the 
appropriate control organisms must be used to check the procedure.

Former Burden

    In the former regulation, laboratories had to check catalase, 
coagulase, beta-lactamase, and oxidase reagents using a positive and 
negative control material each day of use. In addition, the 
laboratories had to check bacitracin, optochin, ONPG, XV, X, and V 
disks or strips using a positive and negative control material each 
week of use. We estimate that most bacteriology laboratories operate an 
average of 6 days per week; therefore, we allowed an average of 2.5 
minutes per day to document the results of control testing for the 
reagents listed above. This resulted in the former burden, 2.5 min./day 
x 24 days/month = 60 min./month = 1 hr./month 1 hr./month x 12 months/
year = 12 hrs./laboratory/yr.
    Under the former regulation, the estimated burden for documenting 
control testing for the reagents above was 27,443 bacteriology 
laboratories x 12 hrs./yr. = 329,316 hrs./yr.

Change in Burden

    In this final rule, we are allowing laboratories to check each 
batch, lot number and shipment of reagents (catalase, coagulase, and 
oxidase), disks (bacitracin, optochin, ONPG, X, V, and XV), stains, 
antisera, and identification systems for positive and negative 
reactivity, and graded reactivity if applicable. For purposes of 
calculating the burden, we are assuming that laboratories receive a new 
shipment of reagents on the average of once per month. Since the burden 
with documenting control testing for susceptibility tests remain the 
same, we are considering the burden for documenting control testing for 
this subspecialty to be reduced by 2.5 min./day x 23 days/month = 57.5 
min./month = 0.96 hrs./month 0.96 hrs./month x 12 months/yr. = 11.5 
hours/ laboratory/yr.
    The total estimated reduction in burden for this requirement is 
27,443 bacteriology laboratories x 11.5 hrs./yr. = 315,595 hrs./yr.

Burden in This Final Rule

    The estimated burden for documenting control testing for 
bacteriology reagents under this final rule is 329,316 hrs./yr.--
315,595 hrs./yr. = 13,721 hrs./yr.
Section 493.1262 Standard: Mycobacteriology
    For the subspecialty of mycobacteriology, in this final rule at 
paragraph (a), each day of use, the laboratory must check all reagents 
or test procedures used for mycobacteria identification with at least 
one acid-fast organism that produces a positive reaction and with an 
acid-fast organism that produces a negative reaction.

Former Burden

    In the former regulation, we included the requirements to document 
the results of control testing with the general QC procedures. However, 
since these documentation requirements are now under the condition, 
Analytic systems at Sec.  493.1250, we have removed these documentation 
requirements from the general QC procedures and placed them in the 
subspecialty of mycobacteriology at Sec.  493.1262.
    In the former regulation, the laboratory was required, each day of 
use, to check all reagents or test procedures for mycobacteria 
identification with an acid-fast positive control organism (except the 
iron uptake test, which also requires a negative control). Assuming 
that only 35.4 percent (see section VII of this final rule, Regulatory 
Impact Analysis) of mycobacteriology laboratories perform 
identification procedures, and test an average of twice weekly, the 
former burden for documenting the positive control reaction for 
mycobacteria identification reagents and tests can be estimated as 2 
min/day x 8 days/month = 16 min./month = 0.27 hrs./month x 12 months/
yr. = 3.24 hrs./laboratory/yr.
    The total estimated burden for documenting the positive control 
result is 1,127 mycobacteriology laboratories x 3.24 hrs./yr. = 3,651 
hrs./yr.
    As mentioned previously, the former regulation also required that 
the laboratory check positive and negative control materials for 
fluorochrome acid-fast stains each week of use and check a positive 
control material for other acid-fast stains each week of use. The 
former burden for all mycobacteriology laboratories to document these 
control results is estimated as 1 min/day x 4 days/month = 4 min./month 
x 12 months/yr. = 48 min./laboratory/yr. = 0.8 hrs./laboratory/yr.
    The total estimated burden for documenting control testing for 
acid-fast and fluorochrome acid-fast stains is 3,185 mycobacteriology 
laboratories x 0.8 hrs./yr. = 2,548 hrs./yr.
    The former total burden for documenting control testing for 
mycobacteria identification reagents and tests, and acid-fast, and 
fluorochrome acid-fast stains was 3,651 hrs./year + 2,548 hrs./year = 
6,199 hrs/yr.

Change in Burden

    Since documentation of the positive control reaction was previously 
required for mycobacteria identification reagents and tests and the 
number of laboratories performing mycobacteriology remains constant, we 
also estimated the increase in burden for documenting the negative 
control material for identification reagents and tests to be one-half 
the previous burden, which is \1/2\ of 3,651 hrs./yr. (from above) = 
1,826 hrs./yr.
    The change in burden for increasing the frequency of acid-fast and 
fluorochrome acid-fast stains to daily and adding a negative acid-fast 
stain result is calculated as 1.5 min/day x 26 days/month = 39 min./
month = 0.65 hrs./month x 12 months/yr. = 7.8 hrs./laboratory/yr.
    The total increase in burden for these documentation requirements 
for acid-fast and fluorochrome acid-fast stains is 3,185 laboratories x 
7.8 hrs./yr. = 24,843 hrs./yr.
    The total increase in burden for documenting control testing for 
mycobacteria identification reagents and tests, acid-fast, and 
fluorochrome acid-fast stains is 1,826 hrs./yr. + 24,843 hrs./yr. = 
26,669 hrs./yr.

Burden in This Final Rule

    The total estimated burden under this final rule for documenting 
control testing for mycobacteria identification reagents and tests, 
acid-fast, and fluorochrome acid-fast stains is 6,199 hrs./yr. + 26,669 
hrs./yr. = 32,868 hrs./yr.
Section 493.1263 Standard: Mycology
    In the former regulation for mycology, each week of use, the 
laboratory was required to check all procedures for mycological 
identification (including germ tube test) using an organism that 
produces a positive reaction. Under this final rule, the requirement is 
eliminated. This deletion results in the QC requirements for the germ 
tube test to default to the general QC requirements at Sec.  
493.1256(e)(1). The general requirements specify QC testing with each 
new batch, lot number or shipment of reagents. Because this is a 
minimal decrease (we estimate the change in frequency from weekly to 
monthly) in burden for documenting the result of a

[[Page 3681]]

single control, we are unable to accurately estimate the change.
    Similarly, in paragraph (a), the laboratory must check each batch, 
lot number and shipment of lactophenol cotton blue for intended 
reactivity with control organism(s). Previously, control testing of 
this stain was required daily. As described above, since the decrease 
in this burden for documenting a single control result is minor, we are 
unable to accurately estimate the change.
Section 493.1269 Standard: Hematology
    In the former regulations for the specialty of hematology, under 
paragraph (b), nonmanual hematology testing systems, excluding 
coagulation, the laboratory was required to include two levels of 
control materials each 8 hours of operation. In this final rule, this 
requirement has been revised from every 8 hours to each day of testing 
under Sec.  493.1256 and results in decreased reporting.
    The revisions to this requirement result in a decrease in 
documenting control results since the requirement has been revised from 
every 8 hours to each day of testing.
    Previously, we had included these reporting requirements with the 
general QC procedures. However, since these requirements are now under 
the condition, Analytic systems, at Sec.  493.1250, we have removed 
these hematology requirements from the general QC procedures and placed 
them under Control procedures at Sec.  493.1256.

Former Burden: Hospital and Independent Laboratories

    The total number of laboratories performing hematology testing is 
32,753. Of this total, 5,329 are hospitals, 3,867 are independent 
laboratories, 17,844 are physician's office laboratories (POLs), and 
5,713 fall into a miscellaneous category of others. We assume that this 
burden will affect most hospitals and independent laboratories since 
these laboratories typically operate 24 hours per day for 30 days a 
month. Therefore, the burden for these laboratories is 5 min./day x 30 
days/month = 150 min./month = 2.5 hrs./month 2.5 hrs./month x 12 = 30 
hrs./laboratory/yr. 9,196 hospital and independent laboratories x 30 
hrs./yr. = 275,880 hrs./yr.

Change in Burden: Hospital and Independent Laboratories

    Since this final rule will only require controls once a day, we are 
allowing a \2/3\ decrease in burden for these laboratories. Therefore, 
the decrease in burden will be \2/3\ of 275,880 hrs./yr. = 183,920 hrs/
yr.
    In addition, the new burden for hospital and independent 
laboratories is 275,880 hrs/yr.--183,920 hrs./yr. = 91,960 hrs./yr.

Former Burden: POLs

    For POLs that only perform hematology for 8 hours a day, there is 
no reduction in burden. However, many POLs have operating hours that 
range from 9 to 10 hours a day and these laboratories are currently 
required to run control materials twice a day. In estimating the burden 
for this category of laboratories, we are including the POLs and the 
``other'' category for a total of 23,557 laboratories. In addition, we 
estimate that 50 percent (11,779) of these laboratories operate on a 9 
or 10-hour day for 20 days a month and must run control materials twice 
a day. Therefore, the burden is 3.5 min./day x 20 days/month = 70 min./
month = 1.2 hrs./month x 12 months/yr. = 14 hours/laboratory/yr. x 
11,779 laboratories (operating on a 9 or 10 hour day) = 164,906 hrs./
yr.
    The remaining 50 percent of the POLs that only operate on an 8-hour 
day have no change in burden that is, 1.75 min./day x 20 days/month = 
35 min./month = 0.6 hrs./month 0.6 hrs./month x 12 months/yr. = 7 
hours/laboratory/yr. 11,779 laboratories (operating on an 8-hour day) x 
7 hours/yr. = 82,453 hrs./yr.

Change in Burden: POLs

    In this final rule, all laboratories will only be required to run 
control materials once each day. Therefore, the POLs operating on a 9 
or 10-hour schedule will have their burden decreased by 50 percent. The 
estimated decrease in burden for this group of laboratories under this 
requirement is 11,779 POLs (operating on 9 or 10 hour day) x 7 hrs./yr. 
= 82,453 hrs./yr.

Former Burden: Total

    The total estimated burden was 275,880 hrs./yr. (hospital and 
independent laboratories) + 164,906 hrs./yr. (POLs operating on a 9 or 
10 hour day) + 82,453 hrs./yr. (POLs operating on an 8 hour day) = 
523,239 hrs./yr.

Change in Burden: Total

    The total estimated decrease in burden for this requirement under 
this final rule is 183,920 hrs./yr. (hospital and independent 
laboratories) + 82,453 hrs./yr. (POLs) = 266,373 hrs./yr.

Burden in This Final Rule

    The total estimated burden under this final rule is 91,960 hrs./yr. 
(hospital and independent laboratories) + 164,906 hrs./yr. (total POLs, 
those operating on a 9 or 10 hour day and those operating on an 8 hour 
day) = 256,866 hrs./yr.
Section 493.1273 Standard: Histopathology
    The revisions to this requirement result in an increase in 
reporting from one control slide to two control slides for each group 
of slides for immunohistochemical stains. Previously, we included these 
reporting requirements with the general QC procedures. The requirements 
are now under the condition Analytic systems at Sec.  493.1250 as 
requirements for Histopathology at Sec.  493.1273. Although this is an 
increase in reporting from one control slide to two, we cannot estimate 
the laboratory burden because we do not know the number of laboratories 
that perform immunohistochemical stains or how often the staining is 
performed. Additionally, many of the laboratories performing 
immunohistochemical stains were already testing both a positive and 
negative control material, and some immunohistochemical stains can be 
checked for a negative reaction on the same slide that contains 
positive reactive cells. We expect that this revision will only affect 
a limited number of laboratories, and the increase in burden will be 
small.
Section 493.1278 Standard: Histocompatibility
    In the former Sec.  493.1265(a)(13), the laboratory was required to 
have, at least once each month, each individual performing tests 
evaluate a previously tested specimen as an unknown to verify his or 
her ability to reproduce test results. Records of the results for each 
individual had to be maintained. These requirements are deleted in this 
final rule.

Former Burden

    There is a reduction in burden for this specialty since, in this 
final rule, we are no longer requiring the laboratories to, at least 
once each month, have each individual performing tests evaluate a 
previously tested specimen as an unknown to verify his or her ability 
to reproduce test results. Therefore, we estimate that the former 
reporting burden for this activity to be 3 min./day for each 
individual, or 3 min./day x 1 month = 3 min./month x 12 months/yr. = 36 
min/yr. = 0.6 hrs/individual/yr.
    We estimate an average histocompatibility laboratory to employ 
three individuals. Therefore, the former

[[Page 3682]]

burden is three individuals x 0.6 hrs./yr. = 1.8 hrs/laboratory/yr.
    There are 264 laboratories performing histocompatibility testing; 
therefore, the estimated burden for this requirement in this final rule 
is 264 histocompatibility laboratories x 1.8 hrs./yr. = 475 hrs./yr.

Change in Burden

    Since this burden is not required in this final rule, we estimate 
the decrease in burden to be 475 hrs./yr.
Section 493.1291 Test Report
    The following information collection requirements under paragraph 
(c) are new: The test report must indicate (1) either the patient's 
name and identification number or a unique patient identifier and 
identification number; (2) the test report date; and (3) the specimen 
source, when appropriate.
    While this information collection requirement is subject to the 
PRA, we believe the burden with it is exempt as defined in 5 CFR 
1320.3(b)(2) because the time, effort, and financial resources 
necessary to comply with the requirement are incurred by persons in the 
normal course of their activities.
    If you comment on these information collection and record keeping 
requirements, please mail copies directly to the following:
    Centers for Medicare & Medicaid Services,
    Office of Strategic Operations and Regulatory Affairs, ORDI, DRD-B, 
Attn: Julie Brown, Room N2-14-26, 7500 Security Boulevard, Baltimore, 
MD 21244-1850.
    Office of Information and Regulatory Affairs, Office of Management 
and Budget, Room 10235, New Executive Office Building, Washington, DC 
20503, Attn: Brenda Aguilar, CMS Desk Officer.

VII. Regulatory Impact Analysis

Overall Impact

    We have examined the impacts of this rule as required by Executive 
Order 12866 (September 1993, Regulatory Planning and Review), the 
Regulatory Flexibility Act (RFA) (September 16, 1980, Pub. L. 96-354), 
section 1102(b) of the Social Security Act, the Unfunded Mandates 
Reform Act of 1995 (Pub. L. 104-4), and Executive Order 13132.
    Executive Order 12866 directs 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). A regulatory impact 
analysis (RIA) must be prepared for major rules with economically 
significant effects ($100 million or more in any 1 year). This 
regulation has no budget implications that impact Medicare benefit 
payments. We have, however, performed a complete regulatory impact 
analysis, although the specified thresholds to require a full analysis 
may not have been met.
    The RFA requires agencies to analyze options for regulatory relief 
of small businesses. For purposes of the RFA, small entities include 
small businesses, nonprofit organizations, and government agencies. 
Most hospitals and most other providers and suppliers are small 
entities, either by nonprofit status or by having revenues of $11.5 
million or less in any 1 year. For purposes of the RFA, all 
laboratories are considered to be small entities. Individuals and 
States are not included in the definition of a small entity.
    In addition, section 1102(b) of 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 604 of the RFA. For 
purposes of section 1102(b) of the Act, we define a small rural 
hospital as a hospital that is located outside of a Metropolitan 
Statistical Area and has fewer than 100 beds.
    Section 202 of the Unfunded Mandates Reform Act of 1995 also 
requires that agencies assess anticipated costs and benefits before 
issuing any rule that may result in an expenditure by State, local, or 
tribal governments, in the aggregate, or by the private sector, of $110 
million. This final rule does not mandate any requirements for State, 
local, or tribal governments, or by the private sector. Therefore, we 
certify that this rule would not have a significant economic impact on 
a substantial number of small entities or a significant impact on the 
operations of a substantial number of small rural hospitals.
    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. We have determined that this final rule does not 
significantly affect States' rights, roles, and responsibilities.

A. Executive Summary

    This final rule includes changes that will impact many laboratories 
and indirectly impact manufacturers of test systems and controls. Most 
laboratories that perform nonwaived testing will be affected. This 
includes laboratories performing unmodified moderate complexity testing 
approved or cleared by the FDA, and laboratories testing in 
microbiology, syphilis serology, immunology, and hematology. Although 
we had insufficient data and information to calculate some of the costs 
and savings that may result from these changes, we estimate the overall 
impact will result in a savings of approximately $23 to $38 million the 
first year and $101 to $166 million over the next 5 years (Tables 1 and 
2). The term ``savings'' as used in this RIA is defined as reduced 
compliance costs for laboratories subject to the CLIA regulations.
    The most significant change in this final rule is related to the 
delayed effective dates (phase-in period) that allowed laboratories 
performing unmodified moderate complexity testing approved or cleared 
by the FDA to meet certain general QC requirements. Laboratories 
performing this type of testing did not have to verify methods before 
their introduction for patient testing or to periodically verify 
calibration. As shown in Table 1, we expect this change to immediately 
impact 29,601 Certificate of Compliance and COLA-accredited 
laboratories. We estimate the cost of completing the QC phase-in period 
to be between $28.3 million and $37.1 million the first year and 
between $124.1 and $162.5 million over the next 5 years.
    Additional changes in this final rule will impact laboratories 
performing various specialties and subspecialties. The impact of these 
changes will vary depending on the volume and frequency of testing 
being done in each specialty or subspecialty.
    Overall, the changes in microbiology will result in significant 
savings of approximately $55.9 million the first year and $245.2 
million over the next 5 years. The changes in bacteriology and mycology 
are based on data demonstrating that for several reagents, QC is not 
required as frequently as required under the previous regulation. We 
assume the changes in bacteriology will affect 27,443 laboratories and 
result in immediate savings of $62.4 million and aggregate savings of 
$273.7 million over the next 5 years. In addition, we expect changes in 
mycology to affect 9,059 laboratories with immediate annual savings of 
$1.4 million and approximately $6.1 million savings over the next 5 
years. For mycobacteriology, we are requiring more frequent QC testing 
and expecting this change to affect 3,185 laboratories with an 
estimated increase in costs of $7.9

[[Page 3683]]

million the first year and $34.6 million over the next 5 years.
    Laboratories performing testing in syphilis serology (7,634), 
immunology (20,665), and hematology (32,753) can perform less frequent 
QC testing. We are unable to estimate the savings because we do not 
know how often the testing will be performed.
    Finally, we are including a number of other changes that we are not 
considering burdensome. In many cases, we expect these other changes to 
have positive impacts; however, we are not able to quantify the 
consequences. Among these changes is the completion of the phase-in 
period for the laboratory director qualification requirement for high 
complexity testing that allowed an individual with a doctoral degree 
and the specified training and experience to qualify as a director of a 
laboratory performing high complexity testing in lieu of board 
certification up until December 31, 2002. To ensure a smooth transition 
to the new provisions for directors of high complexity testing who are 
not board certified (but who have doctoral degrees), we will not be 
holding facilities out of compliance with the provisions of the rule 
concerning directors who are not board certified until the effective 
date of this new rule, to the extent the facilities are otherwise in 
compliance with the requirements for laboratory directors. This means 
that on and after February 24, 2003, individuals with a doctoral degree 
who have not been grandfathered in as directors will need to be board 
certified to serve as directors of laboratories performing high 
complexity testing. The grandfather provision allows those individuals 
with a doctoral degree who have served or are currently serving as high 
complexity laboratory directors and have at least 2 years of training 
or experience, or both; and 2 years of experience directing or 
supervising high complexity testing as of December 31, 2002 to continue 
in this capacity without obtaining board certification. In the absence 
of this provision, the experienced individuals who have a doctoral 
degree without board certification and have served or are serving as 
directors of laboratories performing high complexity testing would be 
ineligible to continue serving as a director, resulting in costly and 
disruptive burdens associated with currently employed individuals 
obtaining board certification and laboratories replacing currently 
serving directors.
    In summary, in the first year, we estimate the sum of all costs to 
be $36.2 to $45.0 million with savings of $63.8 million and a net 
saving of $18.8 to $27.6 million the first year. Over the next 5 years, 
we estimate the sum of all costs to be $158.7 to $197.3 million, a 
total saving of $279.8 million, and a net saving of $82.5 to $121.0 
million.
    In addition to overall monetary savings, this analysis acknowledges 
the potential for improvements in test accuracy and lower error rates 
in patient testing. We expect there to be improvements in the accuracy 
of patient testing and in accuracy of moderate complexity testing 
resulting from performance of method verification and calibration 
verification, and additional QC testing in mycobacteriology. We also 
expect more timely identification of potential laboratory errors 
resulting from the grading of more proficiency testing (PT) challenges.

                    Table 1.--Impacts Due To Regulatory Changes: First Year and 5 Year Totals
----------------------------------------------------------------------------------------------------------------
                                                First year                             5 Year total
                                 -------------------------------------------------------------------------------
                                                       Savings (costs)                         Savings (costs)
                                    Labs affected          [dagger]         Labs affected          [dagger]
----------------------------------------------------------------------------------------------------------------
Method Verification.............             11,248  ($11.3-20.1).......             29,601  ($49.6-88.0)
Calibration Verification........             29,601  (17.0).............             29,601  (74.5)
Microbiology Changes............  .................  ...................  .................  ...................
Bacteriology....................             27,443  62.4...............             27,443  273.7
Mycology........................              9,059  1.4................              9,059  6.1
Mycobacteriology................              3,185  (7.9)..............              3,185  (34.6)
Microbiology Total..............  .................  55.9...............  .................  245.2
Less QC for Other Specialties...  .................  ...................  .................  ...................
Syphilis serology...............              7,634  Unknown savings....              7,634  Unknown savings
Immunology......................             20,665  Unknown savings....             20,665  Unknown savings
Hematology......................             32,753  Unknown savings....             32,753  Unknown savings
    Total.......................  .................  18.8-27.6..........  .................  82.5-121.0
----------------------------------------------------------------------------------------------------------------
[dagger]In millions of dollars.


                                                            Table 2.--Impacts Due To Regulatory Changes: Annual Impacts Over 5 Years
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                      Savings (costs)[dagger]
                                 ---------------------------------------------------------------------------------------------------------------------------------------------------------------
                                            Year 1                     Year 2                     Year 3                     Year 4                    Year 5                 5-Year total
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Method Verification.............  ($11.3-20.1).............  ($10.6-18.8).............  ($9.9-17.6)..............  ($9.2-16.4)..............  ($8.6-15.3).............  ($49.6-88.0)
Calibration Verification........  (17.0)...................  (15.9)...................  (14.8)...................  (13.9)...................  (13.0)..................  (74.5)
Microbiology Changes:             .........................  .........................  .........................  .........................  ........................  ........................
    Bacteriology................  62.4.....................  58.3.....................  54.5.....................  50.9.....................  47.6....................  273.7
    Mycology....................  1.4......................  1.3......................  1.2......................  1.1......................  1.1.....................  6.1
    Mycobacteriology............  (7.9)....................  (7.4)....................  (6.9)....................  (6.4)....................  (6.0)...................  (34.6)
                                 ----------------------------
        Microbiology Total......  55.9.....................  52.2.....................  48.8.....................  45.6.....................  42.7....................  245.2
                                 ============================
Less QC for Other Specialties:
    Syphilis serology...........  Unknown..................  Unknown..................  Unknown..................  Unknown..................  Unknown.................  Unknown
    Immunology..................  Unknown..................  Unknown..................  Unknown..................  Unknown..................  Unknown.................  Unknown

[[Page 3684]]

 
    Hematology..................  Unknown..................  Unknown..................  Unknown..................  Unknown..................  Unknown.................  Unknown
                                 ----------------------------
        Total...................  18.8-27.6................  17.5-25.7................  16.4-24.1................  15.3-22.5................  14.4-21.1...............  82.5-121.0
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
[dagger] In millions of dollars.
Changes discounted at 7 percent compounded annually after Year 1.

B. Introduction

    The changes in this final rule will have some impact upon nearly 
all laboratories performing nonwaived testing. The nature and magnitude 
of the specific effects on any particular laboratory will depend upon 
the volume and types of testing performed and the QC requirements it 
met under the former regulation. The most significant impact will be on 
laboratories performing unmodified moderate complexity testing approved 
or cleared by the FDA that have been following the minimal QC 
requirements provided during the QC phase-in period. With the 
completion of the phase-in, these laboratories may now be required to 
follow more stringent QC procedures.
QC Phase-in Requirements
    Under the February 28, 1992 final rule with comment period 
implementing the Clinical Laboratory Improvement Amendments of 1988 
(CLIA), many laboratories that had never been regulated were required 
for the first time to establish and perform minimum QC and quality 
assurance practices. Most previously unregulated laboratories were 
performing primarily waived or moderate complexity testing using 
unmodified commercial test systems. Acknowledging the burden of coming 
under regulation for the first time, we created a phase-in period that 
allowed laboratories performing unmodified moderate complexity testing 
approved or cleared by the FDA to perform less stringent QC procedures 
than laboratories performing modified moderate complexity or high 
complexity testing. In addition, our intent was that when the phase-in 
period was complete, all laboratories performing nonwaived testing 
would be subject to the same QC requirements. This final rule is ending 
the phase-in period for QC that had been extended to December 31, 2002. 
The QC requirements for laboratories performing unmodified moderate 
complexity testing are now essentially equivalent to the requirements 
for modified moderate complexity, and high complexity testing.
    As part of the QC phase-in, the FDA was to establish a process for 
review and clearance of manufacturers' test system instructions for 
compliance with certain CLIA QC requirements. This provision would have 
allowed laboratories to meet the CLIA QC requirements by following the 
manufacturers' FDA-approved or cleared instructions. However, because 
the CLIA program is user fee funded, we decided it would be prudent to 
wait until the phase-in period ended before implementing the FDA QC 
review. This afforded us the survey experience necessary to determine 
whether an additional FDA review process beyond that already in place 
as part of premarket review would be of benefit to laboratories. We 
realized through our experience inspecting laboratories that an 
additional FDA review would not be of such benefit. Therefore, this 
prospective provision was removed in this rule.
Moderate Complexity Testing
    With implementation of this final rule, laboratories performing 
unmodified, FDA approved or cleared moderate complexity testing must 
now, as applicable--
    [sbull] Augment procedure manual instructions;
    [sbull] Monitor laboratory environmental conditions that affect 
reagent storage and test system operation;
    [sbull] Verify or establish performance specifications for newly 
introduced test systems;
    [sbull] Record or document equipment maintenance and function 
checks;
    [sbull] Perform calibration verification; and
    [sbull] Follow control procedures that monitor the accuracy and 
precision of the testing process.
    These changes will primarily impact Certificate of Compliance and 
COLA-accredited laboratories, because these laboratories perform the 
bulk of the commercial, unmodified moderate complexity testing that was 
subject to the QC phase-in requirements.
Moderate and High Complexity Testing
    This final rule updates requirements and recognizes the 
improvements in technology and stability of reagents by reducing the 
frequency of QC testing in several specialty and subspecialty areas 
that include both moderate and high complexity testing. For the 
following specialties and subspecialties, we reduced the frequency of 
QC testing, relieving laboratory burden and lowering the cost per test:
    [sbull] Decreased frequency of QC testing for bacteriology and 
mycology reagent checks.
    [sbull] Decreased frequency of QC testing for general immunology 
and syphilis serology to daily testing from concurrent with patient 
testing.
    [sbull] Decreased frequency for hematology QC testing to each day 
of use from each 8 hours of operation.
    For the subspecialty of mycobacteriology, we increased the 
frequency of QC testing for the following:
    [sbull] Added a requirement for testing negative controls to check 
stains and reagents.
    [sbull] Increased frequency for checking fluorochrome and acid fast 
stains.
Laboratory Director
    We are completing the phase-in qualification requirements for high 
complexity laboratory director that allows individuals with a doctoral 
degree to qualify based on training and experience in lieu of board 
certification until February 24, 2003. With the implementation of this 
final rule on February 24, 2003, board certification will be required. 
To ensure a smooth transition to the new provisions for directors of 
high complexity testing who are not board certified (but who have 
doctoral degrees), we will not be holding facilities out of compliance 
with the provisions of the rule concerning directors who are not board 
certified until the effective date of this new rule, to the extent the 
facilities are otherwise in compliance with the requirements for 
laboratory directors. This new final rule permits those individuals who 
qualified under the

[[Page 3685]]

phase-in provision and have served or are serving as directors of 
laboratories performing high complexity testing and have at least 2 
years of training or experience, or both, and 2 years of experience 
directing or supervising high complexity testing to continue to serve 
as directors.
Miscellaneous Changes
    There are a number of minor, miscellaneous changes. Some, like the 
change in the consensus requirements for PT grading from 90 percent to 
80 percent, are the result of comments made to the former regulation. 
For the most part, these changes are considered to have no significant 
positive or negative impact. We consider many of them to be 
clarifications of implied requirements, or standard laboratory 
practices already in place, such as the requirement for laboratories to 
verify accuracy of analytes, subspecialties and specialties assigned a 
PT score that does not reflect the laboratories' actual test 
performance. In many cases, we have moved specific sections to make the 
regulation fit within the new regulatory framework (movement of the 
specimen through the laboratory) and to make the requirements easier to 
read and comprehend. While we expect positive benefits from these 
clarifications, it would be impossible to quantify these benefits.

C. Methodology and Approach

Basis for Estimates and Reliability of Projections
    These projections are based upon some necessary assumptions 
concerning the current and future status of laboratory practices, 
technological advances, and the marketplace, making some degree of 
inaccuracy unavoidable. As each change is considered, the assumptions 
are stated. Due to the limitations in our data and information, we used 
a range of reasonable alternatives to estimate future events and 
reflect our degree of uncertainty. For much of this analysis, we use 
well-defined data from CMS Online Survey and Certification Reporting 
System (OSCAR) (2001) concerning laboratory demographics and test 
volume. When using less defined data, we made projections on the more 
costly side to provide an estimation of maximal impact.
    We estimate the impact of these regulatory changes for those 
entities that these changes may affect, and we project the impact over 
the next 5 years. The completion of the QC phase-in period affects a 
portion of laboratories performing unmodified moderate complexity 
testing cleared by the FDA. Other changes in specialty and subspecialty 
QC requirements affect laboratories performing both moderate and high 
complexity testing. The changes in the high complexity laboratory 
director requirements primarily affect laboratories performing high 
complexity testing that need to hire a director on or after February 
24, 2003. As appropriate for each specific change, in addition to the 
impacts on laboratories, we considered the potential impacts on 
manufacturers of laboratory test systems, controls, and calibration 
materials, and possible impacts on patients.
    For this analysis, CDC used the services of Research Triangle 
Institute (RTI) to assist with data collection and cost-benefit 
analyses. RTI used data concerning current testing practices to 
estimate both immediate consequences and the impact over the next 5 
years. A 7 percent discount rate was applied for projections after the 
first year, consistent with OMB recommendations (Economic Analysis of 
Federal Regulations under Executive Order 12866). Both RTI and HHS have 
sought data from a number of sources, including scientific articles, 
Government reports, CMS data, CDC studies, including data from CDC 
cooperative agreements, industry reports, reports by marketing 
consultants, interviews with manufacturers and laboratorians, and 
studies by professional groups, like the American Medical Association.
    For each specific regulatory change, we outline the parties these 
changes will affect, methodological approach, necessary assumptions and 
limitations in the reliability of the conclusions, and possible 
alternatives.

D. Impacts

    This discussion of regulatory impacts is organized as follows:
    [sbull] Section 1 contains the demographics of the laboratories 
that the completion of the QC phase-in will impact.
    [sbull] Section 2 has specific provisions not required during the 
phase-in period that certain laboratories will now need to meet.
    [sbull] Section 3 has changes in specialty and subspecialty QC, 
including changes in microbiology, immunology, syphilis serology, and 
hematology.
    [sbull] Section 4 has the completion of the phase-in requirements 
for laboratory directors.
    [sbull] Section 5 contains miscellaneous changes, Including the 
change from 90 percent to 80 percent consensus requirements for PT 
results grading.
    In this final rule impact analysis, for each regulatory change, as 
appropriate, our discussion is organized under the following topics:
    [sbull] Rationale.
    [sbull] Methodology.
    [sbull] Benefits.
    [sbull] Costs.
    [sbull] Alternative approaches.
1. Laboratories Affected by Completion of the QC Phase-in 
Characteristics of Affected Laboratories Laboratory Demographics
    The total number of certified and exempt laboratories in the United 
States (U.S.) is 174,856 (Table 5). This number includes a total of 
168,688 CLIA-certified laboratories (96 percent), consisting of 91,540 
laboratories with Certificates of Waiver (52 percent), 38,304 with 
Certificates for Provider-Performed Microscopy (PPM, 22 percent), 
22,720 with Certificates of Compliance (13 percent), and 16,124 with 
Certificates of Accreditation (9 percent) (OSCAR, April 2001). In 
addition, there are 6,168 laboratories in the CLIA-exempt States of New 
York and Washington (4 percent).
    This final rule will not affect the 74 percent of clinical 
laboratories holding Certificates of Waiver and PPM (129,844 
laboratories). Laboratories with a Certificate of Waiver are only 
subject to limited CLIA requirements, they must only perform waived 
tests and tests cleared by the FDA for home use, follow manufacturer's 
instructions for testing, and maintain their waived certificates. 
Laboratories with a Certificate for PPM procedures must meet applicable 
requirements in subparts J and K of this final rule (formerly subparts 
J, K, and P). PPM procedures were not under the QC phase-in; therefore, 
PPM procedures were subject to the more stringent requirements in 
subpart K of the February 28, 1992 final rule with comment period. 
However, there are no QC materials for most PPM procedures.
    For this analysis, we assume that all Certificate of Compliance 
laboratories perform some moderate complexity testing and that these 
laboratories have been meeting only the minimum QC requirements for 
FDA-cleared, unmodified moderate complexity test systems under the 
requirements of the QC phase-in period. In addition, we assume the 
completion of the QC phase-in would affect all of these laboratories 
(22,720 laboratories or 13 percent).
    Similarly, we assume that the completion of the QC phase-in will 
affect the COLA-accredited laboratories because COLA's requirements are 
equivalent to the CLIA QC phase-in requirements. Therefore, these 
changes

[[Page 3686]]

will impact COLA laboratories (6,881 laboratories, 4 percent) when COLA 
revises its requirements to be equivalent to this final rule. 
Laboratories accredited by organizations other than COLA currently have 
QC requirements that are more stringent than those under the CLIA QC 
phase-in. With the adoption of the requirements in this final rule, 
CLIA requirements will more closely resemble these accrediting 
organizations' standards for QC.
    Therefore, we estimate that these QC changes will immediately 
affect 29,601 laboratories (17 percent of the Nation's laboratories). 
These laboratories consist of those with a Certificate of Compliance 
(22,720) and COLA-accredited (6,881) laboratories. The 22,720 
Certificate of Compliance laboratories that this QC change may affect 
consist of 1,392 Hospital (6 percent of laboratories with a Certificate 
of Compliance), 2,593 Independent (11 percent), 14,687 physician office 
laboratories (POLs) (65 percent), and 4,048 Other (18 percent) 
laboratories (Table 3). Since the majority of COLA laboratories are 
POLs (95 percent, COLA estimate), we assume all COLA laboratories are 
POLs for this analysis. The estimated total number of POLs that these 
QC changes will impact is 21,568, which comprise the largest portion of 
the 29,601 laboratories (73 percent) we estimated will be affected by 
this regulation. However, the affected POLs constitute only 22 percent 
of all U.S. POLs and 12 percent of all laboratories in the country. The 
vast majority (77 percent) of POLs hold Certificates of Waiver or PPM. 
In addition, changes in this final rule will not immediately affect 
most U.S. hospital laboratories because they are typically accredited, 
rather than Certificate of Compliance laboratories. The additional 
laboratory types in the CMS OSCAR (2001) database classified as 
``Independent,'' are typically referral testing sites, and ``Other'' 
laboratories generally perform testing at a variety of healthcare sites 
including home health testing and nursing homes.
    Although the percentages of laboratories with each certificate type 
remained relatively stable over the past several years, the absolute 
numbers show trends toward lower complexity certificates (waiver and 
PPM). For example, from 1998 to 2001, the number of laboratories with 
Certificates of Compliance decreased by 20 percent (5,604), and an 
increase occurred for both Waiver (+9 percent; 7,628) and PPM (+12 
percent; 3,988) laboratories (Table 4). We expect this trend to 
continue in the future because of the widening availability of waived 
tests, many of which are considered important for on-site testing in 
POLs. Therefore, the long-term impact of this regulation may be 
mitigated by this continuing decrease in the number of Certificate of 
Compliance laboratories.

                                                      Table 3.--Certificate Type by Laboratory Type
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                 Certificate type \1\
                                                         -----------------------------------------------------------------------------------------------
                                                             Compliance         Waiver       Accreditation         PPM          State exempt      All
                   Laboratory type \5\                   --------------------------------------------------------------------       \4\       ----------
                                                                                                                             -----------------
                                                            N \2\   % \3\      N       %        N       %        N       %        N       %        N
--------------------------------------------------------------------------------------------------------------------------------------------------------
Hospital................................................     1,392     15     1,231     14     5,475     62       224      3       498      6      8,820
Independent.............................................     2,593     51       910     18       937     18       131      3       515     10      5,086
Physician Office........................................    14,687     15    42,927     44     6,416      7    31,510     33     1,391      1     96,931
Other...................................................     4,048      7    46,472     76     3,296      5     6,439     10     3,764      2     64,019
All.....................................................    22,720     13    91,540     53    16,124     10    38,304     22     6,168      2   174,856
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ OSCAR, 2001.
\2\ Number of Laboratories.
\3\ Column Percent.
\4\ Data from NY and WA States.
\5\ Self Reported.


                               Table 4.--Changes in Certificate Type, 1998 to 2001
----------------------------------------------------------------------------------------------------------------
                                                    1998             1999             2000             2001
            Certificate type \1\             -------------------------------------------------------------------
                                                N \2\   % \3\      N       %        N       %        N       %
----------------------------------------------------------------------------------------------------------------
Compliance..................................    28,324     17    27,819     16    25,145     15    22,720     13
Waiver......................................    83,912     52    87,754     52    89,998     52    91,540     54
Accreditation...............................    16,469     10    17,337     10    15,885      9    16,124     10
PPM.........................................    34,316     21    36,789     22    37,535     22    38,304     22
All.........................................   163,021    100   169,700    100   171,736    100   171,010   100
----------------------------------------------------------------------------------------------------------------
 \1\OSCAR, 2001.
 \2\Number of Laboratories.
 \3\Column Percent.

Specific Impact Dependent on Test Volume and Laboratory Type

    Certificate of Compliance laboratories comprise 13 percent of U.S. 
laboratories and perform 991 million (19 percent) of the 5.3 billion 
tests annually in the U.S. (OSCAR, 2001). Our estimate of 5.3 billion 
tests for the year 2001 is consistent with the estimate of 5.9 billion 
tests for 1996 by Hoerger, Eggleston, Lindrooth and Basker (1997) and 
the estimate of 5.7 billion tests for the year 2000 in an Institute of 
Medicine report (Institute of Medicine, 2000). The average annual test 
volume per Certificate of Compliance laboratory is 43,618; however, the 
test volume distribution is skewed. Most (69 percent) Certificate of 
Compliance laboratories perform less than 10,000 tests per year, with 
42 percent performing less than 2,000. For COLA laboratories, the 
average annual test volume is approximately 5,000 tests per laboratory 
(COLA, personal communication, June 2001), making the aggregate annual 
test volume for all

[[Page 3687]]

COLA laboratories 34 million tests. Among the Certificate of Compliance 
laboratories, POLs and laboratories under the classification as 
``Other'' tend to have low annual test volumes, while Hospital and 
Independent laboratories have higher test volumes (Table 5).
    This final rule will affect some aspect of these laboratories 
differently depending upon their annual test volume and the number of 
different test procedures they perform. Generally, laboratories 
performing a limited number of different tests will be impacted less 
than laboratories performing a greater number of tests. The low volume 
laboratories, POLs and Others, will be less impacted because they tend 
to have more limited test menus than those in Hospitals and Independent 
laboratories. However, the proportionate costs of testing are greater 
in low volume laboratories (Tershakovec, Brannon, Bennett, and Shannon, 
1995) because of the overhead cost, including those related to CLIA.
    Another major determinate of the impact of this final rule that 
correlates with test volume is the extent of quantitative testing 
performed using moderate complexity instrumentation. A CDC survey of 
laboratories found, for example, that among Certificate of Compliance 
laboratories, the use of quantitative testing instrumentation was 
extremely variable. Use of hematology analyzers varied from a low of 36 
percent among Independent laboratories to a high of 77 percent among 
Hospital laboratories; for chemistry analyzers, the lowest frequency 
(20 percent) was among POLs, while Hospital laboratories had the 
highest use (83 percent) (Steindel, Rauch, Simon, and Handsfield, 
2000). This survey was an unbiased on-site inventory of test systems 
and sampling was weighted to reflect the composition of U.S. 
laboratories.
    We also anticipate that among Certificate of Compliance POLs, the 
practice size will affect the magnitude of the impact. Studies also 
show that practice size correlates directly with the extent of on-site 
testing (Ambulatory Sentinel Practitioner Network, 1996). Therefore, we 
expect the aggregate impact of this final rule to be less among solo 
practices since they perform less testing. However, solo practices have 
fewer employees and financial resources to execute aspects of this 
final rule, which may increase burden.

                                        Table 5.--Annual Test Volumes by Laboratory Type, Certificate of Compliance Laboratories Only, Oscar, April 2001
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                     Number and percent of laboratories grouped by annual test volume
                                                                                                Average  ---------------------------------------------------------------------------------------
                                                                     Total number    Total     number of     <=2,00 tests/yr     2,000-10,000 tests/  10,000-25,000 tests/    25,000
                        Laboratory type \1\                               of       number of   tests per ----------------------          yr                    yr                 tests/yr
                                                                     laboratories  tests \2\  laboratory                       -----------------------------------------------------------------
                                                                                                            N \3\      % \4\        N          %          N          %          N          %
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Hospital...........................................................        1,392         354     254,310        444         32         56          4        148         11        744         53
Independent........................................................        2,593         307     118,396        572         22        481         18        433         17      1,107         43
Physician Office...................................................       14,687         147      10,008      6,899         47      4,681         32      1,617         11      1,490         10
Other..............................................................        4,048         183      45,207      1,614         40        968         24        578         14        888         22
    All............................................................       22,720         991      43,618      9,529         42      6,186         27      2,776         12      4,229         19
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ Self-reported.
\2\ In millions.
\3\ Number of laboratories.
\4\ Column percent.

2. Specific Changes Associated with Completion of the QC Phase-in 
Period

a. Procedure Manuals

Rationale

    During the QC phase-in period, laboratories performing commercial, 
unmodified moderate complexity testing must ``have a procedure manual 
describing the processes for testing and reporting patient test 
results.'' With the completion of the phase-in, laboratories performing 
this type of testing will now be subject to more specific, 
comprehensive procedure manual requirements. Some laboratories may need 
to augment their current procedure manuals to meet the new 
requirements. Although we are unable to estimate the number of 
laboratories and the specific procedure manual changes they will need 
to make, we estimate that all Certificate of Compliance and COLA 
laboratories will require changes to their procedure manual.
    In addition, laboratories must now document the dates of initial 
use and discontinuance for each procedure; and all procedures and 
procedural changes must be approved, signed, and dated by the current 
laboratory director before use.

Benefits

    A comprehensive and up-to-date procedure manual is essential to 
ensure reliable and reproducible performance among individuals and is 
considered one hallmark of good laboratory practice and a necessary 
component of quality management.

Costs

    For those Certificate of Compliance and COLA laboratories that need 
to amend procedure manual instructions, the cost will vary depending on 
the extent to which they may need to create procedural elements and the 
number of procedures performed in each laboratory. The cost for each 
laboratory will be the cost of the labor to augment documentation and 
the laboratory director's time in reviewing, signing, and dating 
procedures. We estimate that these costs will be minimal since most 
Certificate of Compliance and COLA laboratories do not perform a large 
number of test procedures and many may already have the documentation. 
We are unable to estimate the total cost for this requirement since we 
have no estimate on the extent to which procedure documentation will be 
necessary.

[[Page 3688]]

b. Test Systems, Equipment, Instruments, Reagents, Materials, and 
Supplies

Rationale

    With the completion of the QC phase-in, laboratories performing 
commercial, unmodified moderate complexity testing must now meet the 
provisions at Sec.  493.1252 for test systems, equipment, instruments, 
reagents, materials, and supplies. During the phase-in, these 
laboratories were required to ``follow the manufacturer's instructions 
for instrument or test system operation and test performance,'' which 
would include most of the requirements listed in Sec.  493.1252. 
However, now laboratories must monitor and document conditions 
essential for ``proper storage of reagents and specimens, accurate and 
reliable test system operation and test result reporting.'' These 
conditions include ``water quality, temperature, humidity, and 
protection of equipment and instruments from electrical interruptions 
and fluctuations that adversely affect patient test results and test 
reports.''

Benefits

    Monitoring and documenting environmental and other conditions 
necessary for proper reagent and specimen storage and test performance 
is essential to ensure quality test results. When conditions are 
outside of the prescribed acceptable range, corrective action can be 
taken. Without monitoring and documentation, laboratories may not be 
aware of conditions that may adversely affect patient test results.

Costs

    The costs to implement this requirement will be minimal and will 
include labor to develop and maintain a monitoring and documentation 
system. We do not know the extent to which the specific commercial, 
moderate complexity procedures used in each laboratory will require 
monitoring of each of these conditions or the extent to which 
laboratories are already performing monitoring and documentation of 
these conditions. Therefore, we are unable to estimate a total cost for 
this requirement.

c. Method Verification

Rationale

    Method verification is performed when a new test is brought into 
the laboratory and before beginning patient testing and result 
reporting. It consists of studies to verify that the laboratory can 
obtain accuracy, precision, reportable range and reference intervals 
with the new test system comparable to the manufacturer's 
specifications. During the QC phase-in period, laboratories could 
introduce testing using commercial, unmodified moderate complexity test 
systems approved or cleared by the FDA without verifying manufacturer's 
performance specifications (accuracy, precision, and reportable range 
of patient test results) before testing patient's specimens. On April 
24, 2003, all laboratories must perform method verification when 
instituting any new moderate complexity test and before testing patient 
specimens, as specified in Sec.  493.1253.

Methodology

    To determine the possible impact, we did an estimate of the cost of 
assays to verify manufacturers' performance claims for commercial, 
unmodified moderate complexity tests expected to be introduced annually 
among the affected laboratories. For this analysis, we assumed that 
existing moderate complexity test systems would be retired and replaced 
with a new test system approximately every 5 years according to data 
available for a small population of laboratories. In addition, for cost 
calculations, we estimated the number of verification data points 
needed and the costs in terms of labor, materials, and reagents to 
perform these studies.
    The cost of method verification is typically greater for 
quantitative tests than qualitative tests. In most cases, fewer 
specimens and less labor and reagents are required to verify the 
performance of qualitative tests. We do not know the fraction of new 
tests that are qualitative, so we treated all tests as if they are 
quantitative to calculate the maximal impact. Also, we assumed that the 
laboratories that this change will affect have not been performing 
method verification. However, we know that some manufacturers currently 
offer on-site verification assistance, and we expect that practice to 
continue; therefore, we may be overestimating the impact.

Estimates of the Incidence of New Test Introduction

    Data describing how frequently new tests or test systems are 
introduced into laboratories were limited. For one estimate, we used 
the percentages of laboratories expected to add zero, one, two, three, 
four, or five moderate complexity tests to their test menus from a 
survey of laboratories participating in the Pacific Northwest 
Laboratory Medicine Sentinel Monitoring Network (LaBeau, Simon, and 
Steindel, 1999). Laboratories were asked how many nonwaived new tests 
they added to their test menus between April 1997 and April 1999. 
Although these percentages are for a 2-year time period, we 
conservatively assumed that all tests were adopted during the last year 
of the period. We assumed that the incidence of test introduction is 
roughly the same for the affected laboratories as for the Sentinel 
Monitoring Network. Multiplying these percentages by the total number 
of laboratories (29,601), we calculated the number of laboratories that 
are expected to add at least one test to their test menus in a year, 
approximately 11,248 (38 percent) (Table 6).

Estimate of Analyzer Replacement

    Because of the small sample size, we were not confident that the 
survey of laboratories in the Pacific Northwest Laboratory Medicine 
Sentinel Monitoring Network accounted for the replacement of existing 
multiple analyte analyzers. Replacement of an obsolete analyzer with a 
new model requires verification for each analyte. Therefore, the cost 
of replacing analyzers depends upon the existing number of analyzers, 
the number of years of operation before replacement, the number of 
tests each analyzer performs, and the labor and reagent cost per assay 
for method verification. We assumed laboratories replace analyzers 
every 5 years and, therefore, compute the number of analyzers of each 
type that would require replacement each year by dividing the number of 
analyzers by five.
    NICLTS data (Steindel, et al 2000) gave us the percentage of 
Certificate of Compliance POL, Hospital, Independent and Other 
laboratories having chemistry, hematology, therapeutic drug, ligand, 
reproductive hormone, and immunology analyzers. To determine the total 
number of each kind of analyzer to be replaced over the next 5 years, 
we multiplied these percentages by the number of Certificate of 
Compliance and COLA laboratories of each laboratory type to obtain the 
number of laboratories having each kind of analyzer, and then totaled 
the analyzers in each laboratory type (Table 7).

Benefits

    To ensure accuracy and precision, it is especially important to 
demonstrate acceptable performance for a new test method before testing 
patient specimens. Comparing results of the new method with the 
manufacturer's claims and the current method, if the method is being 
replaced, can detect biases and problems with

[[Page 3689]]

reproducibility and linearity. Also, an evaluation of the 
appropriateness of the reference interval ensures that the test can 
differentiate a normal result from one suggesting a disease process. It 
is difficult to estimate the number of mistakes that can be averted by 
method verification. However, it is considered a hallmark of good 
laboratory practice to prevent errors when introducing a new test 
system, by verifying acceptable performance of the new methodology 
before testing patient specimens.

Costs

Number of Tests Needed To Verify Method Performance Specifications (Per 
Analyte)

    There are no standards of practice established for method 
verification, and there is great variability in what laboratories 
currently do to verify performance specifications. The NCCLS has 
published several guidelines for verification of the elements of 
acceptable performance. One way to document performance is to use NCCLS 
protocols, document EP15-P for accuracy and precision, EP6-P for 
linearity (reportable range), and C28-A for reference intervals. The 
three separate protocols require a total of 120 assays, at a minimum. 
Reducing this number can be accomplished by performing some of the 
analyses together using the same specimens. Therefore, our estimate 
using the NCCLS protocol, in which we assumed a range of 120 to 150 
assays per analyte or test, may overestimate the number of assays 
required.

Reagent Costs

    We estimated the cost for reagents by obtaining price quotes from 
reagent manufacturers (Beckman-Coulter, Dade-Behring and Roche 
Diagnostics). Because the price estimates vary with test volumes, we 
assumed a moderate test volume with an average cost across analyzers to 
estimate an average reagent cost. We also estimated an average reagent 
cost to be $1.79 per test. We did not include costs for calibration or 
QC materials. However, many manufacturers provide assistance to 
laboratories for method verification, and this assistance many times 
includes providing reagents to the laboratory free of charge. Although 
manufacturers will incur some cost for reagents, the cost is 
significantly less than the retail sales price we quote.

Labor Estimates

    Because we do not know the average number of analytes per test 
system, we assumed a broad range of analyst time (4 to 16 hours) at a 
rate of $17.90 per hour (Ward-Cook and Tannar, 2001). We are also 
assuming 1 hour of laboratory director time at a rate of $33.45 per 
hour (Bureau of Labor Statistics Occupational Outlook Handbook, 2000-
2001 edition).

Materials

    For the NCCLS approach, patient materials would suffice; however, 
these must be tested on a separate analyzer that serves as a reference 
for accuracy determinations. In addition, we are assuming that 
previously tested, stored patient samples would be used; therefore, we 
included locating previously tested patient materials in labor costs.

Total Costs

    Based on the incidence of introduction of individual tests reported 
in the Pacific Northwest Laboratory Medicine Sentinel Monitoring 
Network survey (LaBeau, et al 1999), the cost of the requirement to 
perform method verification among affected laboratories can range from 
$8.3 to $15.3 million the first year (Table 6). Considering the costs 
of method verification for replacement analyzers, the costs can range 
between $3.0 and $4.8 million (Table 7). Therefore, the total first 
year expense for method verification may range from $11.3 to $20.1 
million. The aggregate impact for method verification, with a discount 
over the next 5 years, may range from $49.6 to $88.0 million.

                                                Table 6.--Impact of Method Verification, New Single Tests
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                  Lab
                                            Percent     Number of   Number of  Med tech labor   director    Total labor    Reagent cost     Total cost
             Number of tests                 adding   laboratories    tests    cost (range) *    labor     cost (range)*     (range)*         methods
                                                         adding       added                      cost*                                        (range)
--------------------------------------------------------------------------------------------------------------------------------------------------------
0........................................         62       18,353           0               0          0               0               0               0
1........................................         16        4,736       4,736      $0.34-1.36      $0.16     $0.50-$1.52      $1.02-1.27      $1.51-2.79
2........................................          8        2,368       4,736       0.34-1.36       0.16       0.50-1.52       1.02-1.27       1.51-2.79
3........................................          5        1,480       4,440       0.32-1.27       0.15       0.47-1.42       0.95-1.19       1.42-2.61
4........................................          4        1,184       4,736       0.34-1.36       0.16       0.50-1.52       1.02-1.27       1.51-2.79
5........................................          5        1,480       7,400       0.53-2.12       0.25       0.78-2.37       1.59-1.99       2.37-4.38
                                           .........  ............     26,048       1.87-7.47       0.88       2.75-8.35       5.60-6.99     8.32-15.33
--------------------------------------------------------------------------------------------------------------------------------------------------------
* Millions of dollars


                                              Table 7.--Impact of Method Verification, Analyzer Replacement
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                     Number of
                                        Number of    analyzers        Medical        Laboratory                                        Total replacement
            Analyzer type               analyzers     replaced      technologist      director   Total labor cost*    Reagent cost *         cost *
                                                     each year      labor cost*     labor cost*
--------------------------------------------------------------------------------------------------------------------------------------------------------
TDM..................................        3,230          646        $46.3-185.0        $21.6        $67.9-206.6         $0.45-0.56         $0.51-0.76
Chemistry............................        7,657        1,531        109.6-438.6         51.2        160.9-489.8          1.10-1.38          1.26-1.87
Hematology...........................       12,439        2,488        178.1-712.5         83.2        261.3-795.7          0.27-0.34          0.53-1.13
Ligands..............................        3,404          681         48.7-195.0         22.8         71.5-217.7          0.25-0.33          0.32-0.52
Reproduction.........................          930          186          13.3-53.3          6.2          19.5-59.5          0.27-0.33          0.29-0.39
Immunology...........................          223           45           3.2-12.8          1.5           4.7-14.3          0.06-0.08          0.07-0.09
                                       ...........  ...........      399.3-1,597.1       $186.5      585.8-1,783.7          2.18-2.72         2.98-4.77
--------------------------------------------------------------------------------------------------------------------------------------------------------
 TDM = Therapeutic drug Monitoring.
* Thousands of dollars.
* Millions of dollars.


[[Page 3690]]

    Assumes tests per analyzer: TDM = 2, Chemistry = 15, Hematology = 
1, Ligands, Reproduction & Immunology = 5
    Assumes reagent cost per test: TDM = $2.88, Chemistry = $0.40, 
Hematology = $0.90, Ligands = $3.00, Reproduction = $2.38, Immunology = 
$2.38

Reliability of Estimates

    The impact of method verification on any particular laboratory will 
depend on how many tests are introduced in any given year. The impact 
will be more on laboratories that are frequently expanding test menus, 
replacing test methods or test systems rather than those maintaining 
test menus and test systems. Obviously, any start-up laboratory 
performing nonwaived testing would be verifying the entire test menu. 
Nearly two-thirds of the laboratories in the Pacific Northwest Sentinel 
Network introduced no test systems during the 2-year interval and none 
introduced more than five (LaBeau, et al, 1999). Therefore, we believe 
while our estimates may accurately describe the impact on the universe 
of affected laboratories, for any particular laboratory, we may have 
underestimated or overestimated the consequences.
    Discussions with manufacturers revealed that assistance with method 
verification is often included in the cost of buying or leasing an 
instrument or other new test system, regardless of the size of the 
laboratory. Regardless of whether the manufacturer assists in the 
verification process, the laboratory or the manufacturer or both will 
incur costs. What is relevant to the impact is whether the frequency of 
the method verification will change. Since method verification already 
frequently occurs in the absence of regulation and manufacturers often 
provide assistance, our estimate of the total cost of method 
verification probably overstates the incremental impact of the new 
requirement. However, we were unable to quantify how frequently method 
verification is performed currently, thereby preventing us from 
precisely estimating the incremental change in the frequency of method 
verification when this regulation becomes effective. Therefore, we may 
have overstated or understated the number of assays that laboratories 
will actually do to verify performance.

d. Calibration Verification

Rationale

    During the phase-in period, laboratories performing unmodified 
moderate complexity testing cleared by the FDA performed testing 
without meeting the calibration verification requirement. On April 24, 
2003, the phase-in period ends, and all laboratories must perform 
calibration verification at least every 6 months for each quantitative 
nonwaived test, as appropriate. Calibration verification is done to 
ensure that the test results are accurate throughout the reportable 
range of patient results for each test system.

Methodology

    To determine the impact, we estimated the number of laboratories 
these changes will affect, their current menus of quantitative tests 
for which calibration verification would be applicable, the number of 
data points needed for verification and the costs in terms of labor, 
verification materials and reagents.

Number of Laboratories This Change Will Impact

    We assumed that this QC change will affect all 29,601 laboratories, 
since Certificate of Compliance and COLA laboratories perform some 
moderate complexity testing. In addition, we assumed these laboratories 
have not been performing calibration verification on commercial, 
unmodified moderate complexity test systems.

Laboratory Menus of Tests With Verifiable Calibration

    Calibration verification is performed for quantitative testing. For 
this analysis, we focused on multi-test clinical analyzers for which 
calibration verification materials are commercially available. 
Specifically, we estimated the fraction of laboratories that have 
analyzers for performing quantitative tests for chemistry, therapeutic 
drug monitoring, ligands, reproductive hormone testing, hematology, and 
immunology. By ``ligands'' we mean analytes measured by immunoassay, 
for example carcinoembryonic antigen, cortisol, and folate.

Number of Analytes Per Analyzer

    For the purposes of estimating reagent consumption, we estimated 
the number of analytes being done by multi-test analyzers. We assumed 
that the variability of laboratory types and sizes would affect the 
number of different tests being performed; however, we were unable to 
account for the variability in this model. Because POLs comprise the 
largest portion of the laboratories that these changes will affect and 
POLs tend to have relatively limited test menus, we assumed most 
laboratory menus to be minimal among those laboratories that these 
changes will affect.
    In order to estimate the number of analytes per laboratory, we 
analyzed data from three proficiency testing programs that target POLs 
(Medical Laboratory Evaluation, American Proficiency Institute, and 
College of American Pathologists' Excel) as a gauge of the numbers of 
tests offered among those laboratories these changes will affect. From 
these data, we estimated average test menus of fifteen chemistry 
analytes, two therapeutic drugs, one hematology analyte, and five for 
each ligand, immunology, and reproductive testing analyzer. Using this 
model, the specific number of analytes that must be verified has little 
impact on the estimates because most of the expense is in the 
verification kits.

Number of Data Points To Verify Calibration

    At a minimum, laboratories must check three points in the 
reportable range to verify calibration, that is, the low, mid, and high 
points of the range. Although there is no requirement to perform 
duplicate testing at each level, it adds information about precision 
while adding very little to the cost of the procedure. Therefore, we 
included duplicate testing. We estimated that six data points are the 
minimum for adequate calibration verification, three concentrations in 
duplicate. Since calibration verification must be performed at least 
twice yearly, laboratories must collect a total of at least twelve data 
points for each analyte every year.

Benefits

    We believe that calibration verification can reduce errors in 
patient testing by periodically providing information on the accuracy 
of an assay after it is calibrated, after any major maintenance or 
after problems are detected in routine QC. However, we are not aware of 
any studies demonstrating the affect of calibration verification on 
error rates.

Labor Costs

    For estimates of labor costs, we assumed that 2 hours per year will 
be sufficient for each analyte for both performing the assay and 
inspecting the results for acceptable performance. This estimate may be 
too low in some instances and too high in others. The cost of the 
analyst time, $17.90 per hour, is the 2000 mean wage per hour for a 
staff medical technologist from Ward-Cook and Tannar (2001). In 
addition, we assumed that the labor cost of calibration verification 
per year is the

[[Page 3691]]

time we estimated it takes to perform the calibration verification (2 
hours), multiplied by the analyst wage per hour ($17.90).

Cost of Verification Materials

    Materials used for calibration verification span the reportable 
range of the method, and target values are assigned independently using 
accurate test methods. Acceptable materials are proficiency testing 
material, altered and unaltered previously tested patient specimens, 
primary standards or reference materials, independent calibrators, or 
materials for demonstrating linearity or calibration verification kits. 
For this analysis, we assumed laboratories will purchase calibration 
verification kits. However, all materials mentioned above may be used 
as long as the entire reportable range is tested with at least three 
concentrations and the nominal concentrations are independently 
assigned with a valid test methodology. Also, we assumed that a 
laboratory with any multi-test analyzer would buy a product to verify 
calibration of all tests the analyzer is capable of performing. We may 
be overestimating the cost because some laboratories do not perform all 
tests available on an analyzer, or we may be underestimating the cost 
by not including individual tests that may not be offered on a multi-
test analyzer.
    Our evaluation shows the costs were roughly similar for the various 
calibration verification products. The cost of calibration verification 
kits was obtained from several different suppliers of calibration 
verification materials (College of American Pathologists, CASCO NERL 
Diagnostics, Align, Sigma, R&D Systems, and Streck Laboratories). The 
average cost for a year's worth of calibration verification materials 
for comparable products was used as the cost of verification materials 
for each analyzer type .

Reagent Costs

    We estimated the cost of reagents from price quotes by analyzer 
manufacturers (Beckman-Coulter, Dade-Behring, and Roche Diagnostics). 
This cost varies with test volume. We used the moderate volume estimate 
provided by these manufacturers for each analyzer type, since most of 
the laboratories that these changes will affect perform low to moderate 
test volumes. We calculated the total cost of reagents by multiplying 
the cost of reagents per test times the number of analytes per 
analyzer, the minimum number of tests per calibration verification, and 
the frequency of calibration verification, which we assumed to be, at a 
minimum, biannually.

Scope of Impact

    Based upon these assumptions and estimates, we calculated the total 
cost of the requirement to perform calibration verification for 
laboratories that these changes will affect to be $17.0 million the 
first year, and the discounted cost will be $74.5 million by the end of 
the next 5 years (Table 8).
    The impact to an individual laboratory will be proportional to the 
number of quantitative tests that need calibration verification. Larger 
laboratories with more analyzers and methods will need to perform 
calibration verification on more methods than smaller laboratories with 
fewer methods. Larger laboratories may also have more instrument 
repairs and reagent changes that may make it necessary to perform 
calibration verification more than twice a year. Therefore, large 
laboratories are more likely to incur a greater increase in the cost of 
calibration verification than small laboratories.
    In addition, some manufacturers may furnish calibration 
verification materials and assist in the performance of calibration 
verification as part of their service. We cannot estimate the extent 
that this may happen; therefore, we may have overestimated the total 
cost.

                          TABLE 8.--Impact of Requirement for Calibration Verification
----------------------------------------------------------------------------------------------------------------
                                  Laboratories                  Cost of
                                  affected for  Labor costs  verification    Cost of    Total costs  Total costs
          Test category             each test     per year     materials     reagents       per        per year
                                    category                   per year      per year    laboratory    [dagger]
----------------------------------------------------------------------------------------------------------------
Ther. Drug Monitoring *.........         3,230       $35.80       $413.00       $69.12      $517.77        $1.67
Chemistry.......................         7,657        35.80        707.00        72.00       815.05         6.24
Hematology......................        12,439        35.80        575.00        10.80       621.60         7.73
Ligands.........................         3,404        35.80        207.00        36.00       278.80         0.95
Reproductive....................           930        35.80        158.00       142.80       336.15         0.31
Immunology......................           223        35.80        150.00       142.80       328.10         0.07
                                 ---------------
    Total.......................  ............  ...........  ............  ...........  ...........       16.98
----------------------------------------------------------------------------------------------------------------
* Therapeutic drug monitoring.
[dagger] Cost in millions.

e. Documentation of Maintenance and Function Checks

Rationale

    During the QC phase-in period, laboratories performing commercial, 
unmodified moderate complexity testing were required to ``follow 
manufacturer's instructions for instrument or test system operation and 
test performance.'' Therefore, if the manufacturer had specific 
instrument maintenance procedures or function checks, the laboratories 
were required to perform them. With the completion of the phase-in, 
these laboratories must perform the maintenance and function checks 
according to the manufacturer, but also document their performance and 
results, as appropriate, and ensure that function checks are within the 
manufacturer's established limits before patient testing is conducted 
as specified in Sec.  493.1254.

Benefits

    Documentation of routine instrument maintenance and function checks 
provides a record for the laboratory to attest maintenance was 
performed according to the required schedule and to ensure that 
instrument function is within acceptable limits whenever patient 
testing is performed. This documentation is an essential element of 
good laboratory practice and laboratory quality management.

Costs

    For those laboratories that have not been documenting maintenance 
and function checks, the cost to initiate this

[[Page 3692]]

process will depend on the labor needed to develop a documentation 
system. Subsequent costs will be for the labor necessary to maintain 
documentation, the number of instruments involved and the extent to 
which documentation is not currently being done. We have no data to 
estimate the total cost to fulfill this requirement; however, it will 
be of minimal impact.
f. Control Procedures

Rationale

    The intent of the CLIA regulation was to impose the same 
requirements on all U.S. laboratories, regardless of testing site, in 
order to assure the public that minimum standards for quality testing 
were met wherever testing was performed. Under the QC phase-in 
requirements, laboratories performing testing using unmodified moderate 
complexity test systems approved or cleared by the FDA were required to 
test two levels of control materials each day of testing. Since many 
laboratories had never been regulated, they were given a phase-in 
period to allow them to become accustomed to meeting requirements for 
QC. During the phase-in, laboratories, could through the guidance in 
Appendix C of the State Operations Manual (SOM), use test system 
internal checks and controls, for example, built in procedural or 
electronic checks, as a substitute for one or both levels of 
traditional external liquid controls.
    With the completion of the QC phase-in, all laboratories performing 
nonwaived testing are subject to the requirements specified in Sec.  
493.1256 for control procedures. The minimal number of control 
materials and frequency for control testing remains unchanged, two 
levels of control materials at least once each day of testing. We will 
continue to allow flexibility for laboratories to follow control 
procedures determined to be equivalent to testing two levels of 
external controls each day of testing.
    We are acknowledging that laboratory technology has become simpler 
since the initial CLIA regulations were promulgated, and simplification 
and improvements are continuing. These technological advances may allow 
for control procedures equivalent to the traditional daily evaluation 
of two levels of external control materials, for example, the use of 
internal checks and internal controls or performance of control 
procedures at a frequency other than daily.
    Additionally, laboratories must now meet some requirements for 
control use and acceptability that were not included for FDA-cleared, 
unmodified moderate complexity testing during the phase-in period. This 
includes testing controls in the same manner as patient specimens, 
rotating control testing among all operators who perform specific 
tests, and verifying the criteria for control results acceptability for 
quantitative tests.

Benefits

    The requirements for control procedures between those in effect 
during the phase-in and this final rule are similar. While enforcement 
was permissive during the phase-in, there were no specific guidelines 
for laboratories to follow. With this final rule, laboratories will 
have guidance on what control procedures are acceptable (criteria will 
be specified in the SOM). In addition, the regulatory language is more 
specific, providing laboratories more detailed descriptions of what is 
required. Also, with the recognition that technology has and continues 
to improve, manufacturers will have more incentive to continue 
simplifying and improving technology to further reduce the cost of QC.

Costs

    Most information on the prevalence of the reliance on internal 
checks and controls in lieu of using traditional external controls is 
anecdotal (American Association for Clinical Chemistry, 1999). A study 
by the Pacific Northwest Laboratory Medicine Sentinel Monitoring 
Network (LaBeau, et al, 1999), demonstrates that the majority of the 83 
laboratories completing the survey used mechanisms other than daily 
testing of traditional external liquid controls for a total of 184 
nonwaived tests. These control mechanisms included built-in controls, 
procedural controls, electronic control cartridges or devices, and 
control strips. Although external controls were used with 85 percent of 
these tests, the frequency varied. Only 15 percent used external 
controls daily, while the majority of the laboratories (64 percent) 
used external controls with each kit or lot of reagents. However, this 
study sample size is too small to draw general conclusions about the 
use of control procedures in most laboratories. Since we anticipate 
maintaining the status quo allowing the use of internal checks and 
internal controls, and the testing of external control materials at the 
frequency currently being performed in most laboratories for unmodified 
moderate complexity testing, there will be no impact on the cost.
    All laboratories must now verify control results acceptability for 
quantitative testing. Laboratories affected by the completion of the QC 
phase-in might incur costs to establish this practice, since this is a 
new requirement. This verification is simply done through repetitive 
testing to ensure that the laboratory's results are within the control 
manufacturer's statistical parameters for the particular test system in 
use. We have no data on the current prevalence of this activity for 
those laboratories that this change may affect. For laboratories that 
have not been performing this verification, the costs they will incur 
will be for the reagents and controls for replicate testing and for the 
labor in testing and evaluating the statistical parameters. In many 
cases, replicate control testing can be done concurrent with patient 
testing, if the control results are within the manufacturer's stated 
range, reducing the cost of this requirement. Laboratories not 
performing this verification will use controls at an increased rate; 
however, they may offset this cost by the ability to use more internal 
or procedural QC. We have insufficient data to estimate the total costs 
for this requirement.

Alternative Approaches

    In revising these regulations, we considered maintaining the QC 
phase-in requirements for QC. These phase-in requirements were intended 
to temporarily exempt most previously unregulated laboratories from the 
more stringent QC requirements such as calibration verification and 
method verification. Previously unregulated laboratories have had 
sufficient time to become familiar with regulatory requirements. 
Although few studies have been done linking the performance of QC 
procedures with patient results (Astles, et al, 1998), the standards 
specified in this final rule are generally considered to be basic 
quality requirements. Also, to maintain the phase-in requirements would 
create a permanent inappropriate discrepancy between what is required 
among the laboratories having different types of certificates and 
between moderate and high complexity testing. Accredited laboratories, 
with the exception of those accredited by COLA, and State-exempt 
laboratories are already required to meet more stringent QC practices 
than those allowed during the phase-in. We believe the completion of 
the QC phase-in requirements is in the best interest of the public to 
ensure the minimum quality laboratory standards regardless of testing 
site and the type of testing performed.

[[Page 3693]]

3. Changes in Specialty and Subspecialty QC Requirements
a. Changes to Specific Microbiology QC Rationale
    We are changing the requirements for some specific QC practices in 
microbiology in response to public comments, including recommendations 
made by the American Society for Microbiology (ASM). The changes affect 
the subspecialties of microbiology, including bacteriology, 
mycobacteriology, and mycology.
    In 1996, the ASM (ASM, 1996) reported to the CLIAC a study of QC 
failures for 304 laboratories and nearly 15,000 commercial reagent lots 
representing 21 different bacteriology and mycology tests. QC failure 
rates for the reagents studied were 0.3 percent overall. The individual 
failure rate for each reagent was less than 2 percent, except for X 
factor strips/disks, which was 2.13 percent. The results of this study 
prompted the ASM to propose that reagent QC be required only with each 
new lot for commercial microbiology reagents having a 98 percent or 
greater success rate. On the basis of these study results and ASM's 
recommendations, in this regulation, we are lowering the required 
frequency for reagent QC for several bacteriology tests and two 
mycology tests (Table 9).
    For mycobacteriology, we are increasing some QC requirements based 
on public comments, making them equivalent with standards that already 
exist (Table 9). False positive results have been reported in testing 
for M. tuberculosis (Burman, Stone, Reeves, et al, 1997). At the same 
time, the incidence of infection caused by other mycobacteria requiring 
additional testing for accurate identification is increasing 
significantly. To some extent, false positive results leading to 
inaccurate diagnoses and unnecessary or inappropriate therapy could be 
reduced by including a negative reagent control with biochemical 
identification tests. Therefore, in this regulation, negative controls 
are now required in addition to positive controls each day of use for 
mycobacteriology reagents. In addition, positive and negative controls 
are now required each day of use for acid-fast stains, and each time of 
use for fluorochrome stains. The revised requirements are justified by 
the important public health consequences of accurate and timely 
identification of mycobacteria, including M. tuberculosis.

            Table 9.--Changes to Microbiology QC Requirements
------------------------------------------------------------------------
                                          New regulations (specified in
          Existing regulations                      this rule)
------------------------------------------------------------------------
              Bacteriology
Each day of use, check catalase,         (NC) Each day of use, check
 coagulase, beta-lactamase and oxidase    beta-lactamase, (other than
 reagents and DNA probes using a          cefinase (D)) and DNA probes
 positive and negative control.           using a positive and negative
                                          control.
Each week of use check bacitracin,       (D) Check each batch, lot
 optochin, ONPG, X, and V discs or        number and shipment of
 strips using a positive and negative     reagents (catalase, coagulase,
 control.                                 and oxidase), disks
                                          (bacitracin, optochin, ONPG,
                                          X, V and XV), stains, antisera
                                          and identification systems for
                                          positive and negative
                                          reactivity, and graded
                                          reactivity if applicable.
Each month of use check antisera using   (D) Check each batch, lot
 a positive and negative control.         number and shipment of
                                          antisera when prepared or
                                          opened and once every 6 months
                                          thereafter using a positive
                                          and negative control.
            Mycobacteriology
Each day of use, check iron uptake test  (I) Each day of use, check all
 using a positive and negative acid-      mycobacteriology reagents
 fast organism and check all other        ((NC) iron uptake test) using
 reagents or test procedures using a      a positive and negative acid-
 positive acid-fast organism.             fast organism.
Each week of use check acid-fast stains  (I) Each day of use, check acid
 using positive control.                  fast stains using a positive
                                          and negative controls.
Each week of use, check fluorochrome     (I) Each time of use, check
 acid-fast stains using positive and      fluorochrome stains using
 negative controls.                       positive and negative
                                          controls.
                Mycology
Each day of use, test staining           (D) Check each batch, lot
 materials (lactophenol cotton blue)      number and shipment of
 for intended reactivity.                 lactophenol cotton blue when
                                          prepared or opened for
                                          intended reactivity.
Each week of use, check biochemical      (D) Check each batch, lot
 tests and mycological identification     number and shipment of
 tests (germ tube) with a positive        reagents, disks, stains,
 control.                                 antisera and identification
                                          systems for positive and
                                          negative reactivity.
------------------------------------------------------------------------
D = Decreased QC Testing.
I = Increased QC Testing.
NC = No change.

Methodology

    The number of laboratories impacted by the QC changes for the 
microbiology subspecialties of bacteriology, mycobacteriology, and 
mycology includes laboratories issued a Certificate of Compliance or a 
Certificate of Accreditation performing testing in the applicable 
subspecialties of microbiology according to the CMS OSCAR (2001) 
database. The number also includes the 1,448 laboratories performing 
testing in bacteriology, mycobacteriology, and mycology laboratories in 
the exempt States.
    In estimating the cost of materials for changes to the microbiology 
QC requirements, we used information from several different 
microbiology reagent manufacturers and distributors (Remel, Becton 
Dickinson, and Fisher), including average list prices or suggested 
retail prices for reagents and supplies (we acknowledge some 
laboratories receive lower prices through negotiated discounts or 
purchasing agreements). We estimated the time and amount of reagent 
needed to perform QC testing and maintain records for the affected 
tests in the applicable subspecialties, through discussions with 
experts in microbiology.
    For the tests the QC changes will affect, the cost of QC organisms 
was considered negligible since organisms may be preserved and 
recultivated on an ongoing basis. Although the cost of maintaining 
cultures, including media and supplies, and the time spent in 
preservation and recultivation may be considerable, the changes in this 
final rule will not cause complete elimination of QC organism testing; 
therefore, the cost of culture maintenance will not

[[Page 3694]]

change. On the other hand, in mycobacteriology, negative control 
organisms are now required for biochemical identification tests. 
Although this could result in some initial expense if new organisms 
must be purchased, significant cost should not be incurred, since in 
some cases the same organism may be used as a control for more than one 
test, and some of the organisms used for negative controls may be 
organisms already used as positive controls for different biochemical 
tests.
    For estimating labor costs (the larger component of the QC cost for 
many tests), we used the 2000 mean wage per hour for a staff medical 
technologist (Ward-Cook and Tannar, 2001), divided by 60 minutes per 
hour to calculate the cost per minute ($0.30). The cost of labor is the 
sum of the time required to perform QC and maintain the QC records, 
multiplied by the calculated wage per minute. The total cost of QC per 
test is the sum of the labor and material costs.

Bacteriology

    We estimate that the QC changes for bacteriology will affect 27,443 
laboratories, consisting of 26,610 laboratories in the CMS OSCAR (2001) 
database and an additional 833 bacteriology laboratories in exempt 
States. The changes pertain to reagents commonly used to identify 
bacteria. Although these reagents are primarily used for high 
complexity culture and identification procedures that may not be 
performed in a number of physician office laboratories or laboratories 
that perform only moderate complexity testing, we included all 
bacteriology laboratories in our estimates because some physician 
office laboratories perform high complexity culture and identification 
procedures, and at least one of the reagents may be used for moderate 
complexity tests. We realize the number of bacteriology laboratories 
that these QC changes affect may be overestimated.
    As recommended by ASM, we are reducing QC testing to every batch, 
lot number, and shipment, for 10 commercial bacteriology reagents. 
Under the previous QC requirements for catalase, coagulase, oxidase, 
and beta-lactamase, QC testing was additionally required each day of 
use. The previous QC requirements for bacitracin, optochin, ONPG, X, V, 
and XV strips and disks were to test each week of use after initial 
testing of each batch, lot number, and shipment of reagent. For 
antisera (including Salmonella and Shigella antisera), we are reducing 
the QC testing requirements from every month of use, to every 6 months 
after initial QC testing.

Mycobacteriology

    We expect the QC changes will affect a total of 3,185 
mycobacteriology laboratories in various degrees, depending upon the 
services they provide. This includes 2,903 laboratories in the CMS 
OSCAR (2001) database and 282 laboratories in exempt States. Based on 
estimates of the levels of mycobacteriology testing performed in the 
U.S. (CDC, 1995), all mycobacteriology laboratories perform acid-fast 
stains and could be impacted by the changes to the QC requirements for 
this testing. However, according to the estimates above, only 35.4 
percent (1,127) of mycobacteriology laboratories perform mycobacterial 
organism identification, including 24.4 percent that perform acid-fast 
stains, primary culture, and identification (at least of M. 
tuberculosis complex), and 11.0 percent that perform acid-fast stains, 
primary culture, identification, and drug-susceptibility testing. 
Therefore, this number represents the maximum number of laboratories 
that could be fully impacted by all QC changes for this subspecialty.
    For acid-fast stains, we are now requiring positive and negative 
control organisms to be QC tested each day of use rather than each week 
of use. In addition, we are now requiring that fluorochrome acid-fast 
stains be QC tested each time of use rather than each week of use. 
Although not all mycobacteriology laboratories perform both types of 
stains on a daily basis, the specific percentage of laboratories 
performing each type of stain is unavailable. We conservatively 
estimated that the QC change will affect all mycobacteriology 
laboratories for both staining procedures and will require the 
laboratories to perform QC testing for each procedure at least daily. 
However, professional standards of practice recommend QC for acid-fast 
stains each time of use, and the QC changes will not impact 
laboratories following these guidelines.
    For conventional biochemical reagents and test procedures for 
mycobacterial identification from culture, we are now requiring that a 
negative control organism be tested in addition to a positive control 
organism each day of use. Based on the biochemical tests used for 
mycobacterial identification as listed in Essential Procedures for 
Clinical Microbiology (Eisenburg, 1998), we estimate 10 additional 
negative controls for biochemical tests may be performed by each 
laboratory depending on the organism to be identified. However, our 
estimates of the additional QC required and number of laboratories that 
these changes will impact could be inflated for several reasons. First, 
many mycobacteriology laboratories now use molecular methods for 
organism identification in lieu of conventional biochemical tests (we 
are not changing the QC requirements for molecular methods). According 
to an ASM survey presented to the CLIAC in 1999, 78 percent of the 
responding laboratories performing mycobacterial identification used 
molecular methods. It is likely that this percentage will increase in 
the future as new technology continues to be developed. Second, a 
significant number of mycobacteriology laboratories only identify M. 
tuberculosis and do not use biochemical tests to identify additional 
species of mycobacteria. Last, professional standards and at least one 
accreditation organization already recommend or require a negative 
control in addition to a positive control for each identification test; 
therefore, the increase in the requirement will not impact laboratories 
already meeting these standards. Since sufficient data are not 
available to quantify these considerations, we estimate a maximum of 
35.4 percent of mycobacteriology laboratories will have to perform 
additional QC for conventional biochemical tests.

Mycology

    We are reducing the QC testing for the germ tube test by 
eliminating the positive control each week of use after initial testing 
of positive and negative controls with every batch, lot number, and 
shipment. We are also reducing the QC testing for lactophenol cotton 
blue from checking this stain for intended reactivity each day of use, 
to requiring QC testing only with each batch, lot number, and shipment. 
We do not expect the QC changes to affect all 18,117 laboratories 
performing mycology testing (17,784 mycology laboratories in the CMS 
OSCAR (2001) database and 333 mycology laboratories in exempt States), 
since the impact of decreasing the QC testing will differ among 
laboratories depending on the testing performed and the numbers of 
positive cultures obtained by these laboratories. For both the germ 
tube test and the lactophenol cotton blue stain, we conservatively 
estimate that the reduction in QC testing will affect 50 percent of the 
total laboratories (9,059), those being hospital and independent 
laboratories that would perform the high complexity culture procedures 
that require the use of these reagents.

[[Page 3695]]

Benefits

Bacteriology

    Reducing the QC testing requirements for bacteriology results in a 
significant decrease in costs for the laboratory, including savings in 
reagents, supplies, and labor. To estimate the impact of these 
reductions, the QC cost associated with the changes must be compared to 
the current cost of QC testing. We assumed laboratories are currently 
performing QC testing for each batch, lot number, and shipment of 
reagents; therefore, this practice is not affected by these QC changes. 
For catalase, coagulase, oxidase, and beta-lactamase, eliminating the 
daily QC requirement results in a savings for each of these tests 
equivalent to the cost of the daily QC. Similarly, by eliminating the 
weekly QC requirement for bacitracin, optochin, ONPG, X, V, and XV 
strips and disks, there is a savings for each of these tests equivalent 
to the cost of the weekly QC. For antisera (for example, Salmonella, 
Shigella typing sera), we are reducing QC testing from every month of 
use to testing once every 6 months after the initial QC testing of each 
batch, lot number, and shipment of reagent. Assuming an average shelf 
life of 2 years before expiration results in cost saving of 20 QC 
tests.
    In addition to the direct financial savings in bacteriology 
laboratories, reducing the QC testing will also result in a time 
savings equal to the time previously required to perform the testing 
and maintain QC records on a daily, weekly, or monthly basis. This time 
saving could lead to increased productivity in bacteriology 
laboratories.
    To calculate the savings by reducing requirements for QC testing in 
bacteriology, we estimated the baseline expenses per laboratory for 
performing each QC test. In calculations for beta-lactamase testing, as 
per the ASM study, we assume laboratories use CefinaseTm as 
their method of testing. After estimating the cost per individual QC 
test (positive and negative controls), we then determined the change in 
cost per day, week, and year (Table 10). In determining these changes, 
we considered the decrease in frequency of testing for each reagent 
(previously daily vs. weekly vs. monthly). To calculate weekly changes, 
we used an average of 6 days per week for laboratory operations, 
recognizing that while most hospital laboratories operate 7 days a 
week, physician office laboratories (that perform some culture and 
identification procedures) may only operate 5 days a week. Since we 
estimate all bacteriology laboratories use all tests for which QC is 
reduced, to determine the total annual savings per laboratory, we added 
the QC savings for each individual test.
    To estimate the total annual savings in QC costs for all 
bacteriology laboratories, we multiplied the total annual savings per 
laboratory by the number of laboratories affected (27,443), and 
estimated a total cost savings of $62.4 million the first year.

                                       Table 10.--Change in Cost per Test for Revised Bacteriology QC Requirements
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                    Change  in   Change  in   Change  in
                  Reagent                      Labor             Reagent  amount           Reagent     Total cost   cost  per    cost  per    cost  per
                                               cost*                                         cost       per test       day          week         year
--------------------------------------------------------------------------------------------------------------------------------------------------------
Catalase..................................        $0.60  1 drop........................        $0.08        $0.68       -$0.68       -$4.08     -$212.16
Coagulase.................................         0.60  2 drops.......................         0.17         0.77        -0.77        -4.62      -240.24
Oxidase...................................         0.60  1 drop........................         0.06         0.66        -0.66        -3.96      -205.92
Cefinase..................................         0.60  2 discs.......................         2.65         3.25        -3.25       -19.50    -1,014.00
Bacitracin................................         0.60  2 discs.......................         0.40         1.00        -0.17        -1.00       -52.00
Optochin..................................         0.60  2 discs.......................         0.33         0.93        -0.16        -0.93       -48.36
ONPG......................................         0.60  2 discs.......................         0.98         1.58        -0.26        -1.58       -82.16
X.........................................         0.60  2 strips......................         1.60         2.20        -0.37        -2.20      -114.40
V.........................................         0.60  2 strips......................         1.60         2.20        -0.37        -2.20      -114.40
XV........................................         0.60  2 strips......................         1.60         2.20        -0.37        -2.20      -114.40
Antisera..................................         0.60  2 drops.......................         6.98         7.58        -0.24        -1.46       -75.80
                                           --------------
    Total.................................  ...........  ..............................  ...........  ...........  ...........  ...........   -2,273.84
--------------------------------------------------------------------------------------------------------------------------------------------------------
* Labor cost estimate for each reagent includes one minute to perform QC test and one minute for recording and monitoring QC results.

Mycobacteriology

    Erroneous test results can lead to inaccurate diagnoses and 
unnecessary or inappropriate therapy. When this pertains to M. 
tuberculosis or other mycobacteria currently emerging as significant 
pathogens, it could have substantial cost implications or adverse 
health outcomes due to the side effects of drugs used to treat 
infections caused by these organisms. Therefore, it is critical for 
laboratories to rapidly detect mycobacteria and accurately identify 
individual species within this genus. For laboratories performing acid-
fast and/or fluorochrome acid-fast stains, accuracy is best ensured by 
including positive and negative controls each day (acid-fast) and each 
time (fluorochrome acid-fast) of use. For laboratories using 
conventional biochemical tests to identify mycobacteria, erroneous test 
results can most likely be prevented by including a positive and 
negative control organism for each test each day of use. Although 
difficult to quantify, the increased costs for additional QC testing 
are outweighed by the benefits of prompt, accurate mycobacterial 
detection and identification, and appropriate therapy for mycobacterial 
infections.

Mycology

    Reducing the QC testing requirements for the germ tube test and 
lactophenol cotton blue stain will result in a cost and time savings 
for mycology laboratories. Since weekly QC is eliminated for the germ 
tube test, the financial savings will equal the cost of weekly QC, and 
the time savings will equal the time spent on a weekly basis performing 
and recording QC for this test. For lactophenol cotton blue, required 
QC testing each day of use is now eliminated. The cost and time savings 
resulting from this reduction is based on calculations assuming this 
test is performed an average of twice a week, when positive fungal 
cultures are detected.
    We estimated the savings for QC testing in mycology by determining 
baseline expenses for each germ tube test labor ($0.90) and materials 
($0.73), and each lactophenol cotton blue test labor ($0.60) and 
materials ($0.06), followed by calculation of the weekly and annual 
savings that will be realized

[[Page 3696]]

by reducing the QC frequency for these tests. Since we estimate that 
these changes will affect 50 percent of mycology laboratories, the 
total annual cost savings in mycology will be the annual savings per 
laboratory multiplied by half the number of mycology laboratories 
(9,059), an estimated total cost savings of $1.4 million the first 
year.

Costs

Mycobacteriology

    We estimated the cost for the changes to mycobacteriology QC 
testing in the same manner as we estimated savings for bacteriology 
(Table 11). However, in mycobacteriology, not all laboratories will be 
affected for every test, since no more than 35.4 percent of 
laboratories perform organism identification. Therefore, when 
estimating the overall costs of increasing the mycobacteriology QC 
requirements, we considered the difference in the number of affected 
laboratories in the calculations.
    When calculating costs for the acid-fast and fluorochrome acid-fast 
stains, we estimated that for each test, mycobacteriology laboratories 
would test two QC slides on at least a daily basis. Although QC is 
required each time of use for fluorochrome acid-fast stains (which can 
differ from each day of use), we assume QC would be performed daily and 
that each laboratory performs both acid-fast and fluorochrome acid-fast 
stains daily and will incur an increase in QC testing costs for both 
methods. However, some mycobacteriology laboratories use only one 
method of staining, and some laboratories already check QC slides each 
time of use. The percentage of laboratories using each type of stain 
exclusively or already performing QC each time of use is not available. 
Therefore, our estimate of the cost impact of this increase in QC 
testing is higher than the actual costs that will be incurred. When 
calculating the weekly QC testing costs for acid-fast stains, we used 7 
days for laboratory operations, taking into account the CDC recommended 
turnaround time of 24 hours (Huebner, Good and Tokars, 1993) for 
reporting acid-fast smears.

                                     Table 11.--Change in Cost per Test for Revised Mycobacteriology QC Requirements
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                    Change  in   Change  in   Change  in
                                             Labor  cost         Reagent  amount           Reagent     Total cost    cost per     cost per    cost  per
                                                                                             cost       per test       day          week         year
--------------------------------------------------------------------------------------------------------------------------------------------------------
Identification Tests\1\....................    \2\ $6.00  Variable.....................       $20.46       $26.46       +$7.56      +$52.92   +$2,751.84
Acid-fast Stains...........................     \3\ 1.80  2-3 mL of 3 solutions........         0.61         2.41        +2.41       +14.46      +751.92
Fluorochrome Stains........................     \3\ 1.80  2-3 mL of 3 solutions........         0.60         2.40        +2.40       +14.40      +748.80
                                            --------------
    Total..................................  ...........  .............................  ...........  ...........  ...........  ...........   +4,252.56
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ Estimate includes the following tests: arylsulfatase, 68 degree catalase, semi-quantitative catalase, NaCl tolerance, niacin, nitrate,
  pyrazinamidase, tellurite reduction, Tween 80 hydrolysis, and urease.
\2\ Combined labor cost estimate for each reagent/test includes one minute to perform QC test and one minute for recording and monitoring QC results.
\3\ Labor cost estimate for each stain procedure includes five minutes to perform QC test and one minute for recording and monitoring QC results.

    For conventional biochemical reagents and identification procedures 
used on mycobacterial culture isolates, we calculated the potential 
cost increase for adding a negative control to each test based on 10 
biochemical reagents (or tests) used for mycobacterial identification, 
as listed in Essential Procedures for Clinical Microbiology (Eisenburg, 
1998). Although several additional biochemical tests can be used in the 
conventional scheme of mycobacterial identification, most of these 
tests were not included in our calculations since they are growth tests 
on certain selective media, which would not be subject to increased QC 
requirements. The iron-uptake test was also not included in our 
calculations since a negative control was previously required for this 
test. In estimating the change in cost for these identification 
procedures, the cost of labor for these tests was first calculated for 
a single test and then multiplied by 10. We assume the same approximate 
time is required to perform and record each QC test. The total reagent 
cost was determined by adding the cost of reagents for each individual 
test. The total cost for all 10 tests is the sum of the labor and 
reagent costs. Since in most laboratories these tests are performed 
less frequently than acid-fast stains or bacteriology identification 
tests, our estimates assume that each of these tests would be run twice 
per week. The additional cost for each laboratory per week is equal to 
twice the total cost for all 10 tests, and the additional annual cost 
per laboratory is estimated on the basis of this total weekly cost.
    To estimate the total annual increase in the cost of QC for 
mycobacteriology, we multiplied the increased costs for acid-fast and 
fluorochrome stains by the total 3,185 mycobacteriology laboratories, 
and multiplied the increased costs for conventional biochemical 
identification tests by 35.4 percent of the total number of 
laboratories (1,127), and then added these amounts. We estimated the 
total cost increase would be $7.9 million the first year.

Error Rates

Bacteriology

    We do not expect increased error rates in patient testing for the 
QC changes in bacteriology. As reported in the ASM study, the QC 
failure rates for laboratories participating in the study translated 
into one failure for all reagents surveyed every 53 years (ASM, 1996). 
Since in many cases, a single reagent or test is only a part of a 
bacterial identification scheme, these rare failures are not likely to 
lead to errors in organism identification or patient testing.

Mycology

    We expect no additional errors as a result of the decreased 
requirements for QC in mycology.

Scope of Impact

    The changes in QC requirements for microbiology laboratories will 
result in significant cost savings overall, on an annual and 5-year 
basis, when considering the net effect of the changes being implemented 
in the subspecialties of bacteriology, mycobacteriology, and mycology. 
The decreased QC requirements in bacteriology and mycology are expected 
to impact all U.S. laboratories performing this testing under a 
Certificate of Compliance, Certificate of Accreditation, or State 
exemption. We estimate the total cost savings for each microbiology 
laboratory

[[Page 3697]]

performing bacteriology testing to be $2,274 the first year. By 
multiplying this number by the total number of bacteriology 
laboratories (27,443), we estimate the total savings for bacteriology 
laboratories to be $62.4 million the first year and the overall savings 
over the next 5 years to be approximately $273.7 million for 
bacteriology.
    For mycology, we estimate the total cost savings the first year per 
laboratory will be $153, and the change will affect 9,059 mycology 
laboratories with total savings of $1.4 million. We estimate overall 
savings will be $6.1 million for the next 5 years.
    Although the increase in QC requirements for mycobacteriology will 
result in increased costs for microbiology laboratories conducting this 
testing, the impact will not affect all laboratories to the same 
extent, as previously explained. In fact, laboratories previously 
following professional standards of practice for mycobacteriology will 
not be impacted at all by these QC changes. Mycobacteriology 
laboratories will likely incur increased QC costs for acid-fast and/or 
fluorochrome stains, an estimated maximum increase of $1,501 per 
laboratory the first year, and $4.8 million overall, assuming 
laboratories use both methods of staining, and did not previously test 
controls each time of use. Since only 35.4 percent of mycobacteriology 
laboratories perform organism identification, the impact of increasing 
the QC requirements for certain identification tests will affect 
significantly fewer laboratories. We calculated this increase to cost 
$2,752 per laboratory the first year, with a maximum cost of $3.1 
million overall. However, as explained previously in the 
Mycobacteriology subsection of the Methodology section, we believe this 
cost impact is overestimated for the increased QC for biochemical 
identification tests. Evidence shows that with newer technology, fewer 
laboratories use the older conventional tests, and this is expected to 
further decrease as technology continues to improve. In addition, 
laboratories offering limited services may not use as many biochemical 
identification tests if they only identify a limited number of 
organisms. Last, since professional standards and an accreditation 
organization already recommend or require negative control organisms, 
many laboratories may already be including the controls we are now 
requiring in this regulation. Therefore, the combined annual estimate 
of increased QC costs for mycobacteriology laboratories of $7.9 million 
overall and the next 5 year estimate of $34.6 million are likely 
inflated to some degree.
    To summarize, the total savings in QC testing costs that will 
result from the changes in the microbiology requirements is the sum of 
the savings in the subspecialties of bacteriology and mycology, minus 
the cost increases in the subspecialty of mycobacteriology, a minimum 
total cost savings for microbiology laboratories of $55.9 million the 
first year. The savings projected over the next 5 years are 
approximately $245.2 million.

Alternative Approaches

    For bacteriology and mycology, one alternative approach would be to 
continue to require QC testing for all reagents at the same frequencies 
as specified in the February 1992 regulations. However, there are no 
data that support continuing these frequencies to ensure the quality of 
patient testing. We believe if the previous frequencies were 
maintained, the total financial costs in labor and materials would far 
exceed the possible benefits in detecting problems with reagents. 
Another approach we considered is QC testing less frequently than with 
every batch, lot number and shipment of reagents (catalase, coagulase, 
beta-lactamase, oxidase, and germ tube test), disks and strips 
(bacitracin, optochin, ONPG, X, V, and XV), stains (lactophenol cotton 
blue), and antisera. However, because damage or improper handling of 
each batch, lot, or shipment can result in compromised reagent 
integrity, we did not consider this to be acceptable. We also 
considered leaving the requirement for monthly testing of antisera in 
place, but since there are no data to support this frequency, and the 
ASM data showed the reagents are relatively stable, we considered QC 
testing every 6 months adequate for these relatively expensive reagents 
with extended shelf lives.
    For mycobacteriology, we considered not requiring a negative 
control with daily use of identification reagents, and not requiring QC 
daily for acid-fast stains, and each time of use for fluorochrome 
stains. However, the expense of increasing these requirements is 
relatively small because so few laboratories are impacted and in 
practice the incremental impact of adding a second control is 
relatively small. We cannot quantify the impact on error rates of not 
implementing these changes, but false positive tests in 
mycobacteriology can result in considerable extra expense in patient 
care.
b. Changes in Required QC Frequency for Syphilis Serology, Immunology, 
and Hematology

Syphilis Serology

    We estimated that the reduction in frequency for syphilis serology 
QC testing may affect 7,634 laboratories (Certificate of Compliance 
(3,068), Certificate of Accreditation (4,070), and State-exempt (496)) 
(OSCAR, 2001 and the States of New York and Washington). Laboratories 
will be required to run controls each day patient specimens are tested, 
rather than each time they are tested. For laboratories testing patient 
specimens more than once a day, this change will result in a cost 
savings. However, we cannot estimate the amount of savings, because we 
do not know how many of these laboratories conduct testing more than 
once per day.

Immunology

    There are a total of 20,665 laboratories (Certificate of Compliance 
(9,728), Certificate of Accreditation (10,285), and State-exempt (652)) 
performing immunology testing that may be affected by the reduction in 
the frequency for immunology QC testing. Under this final rule, 
laboratories must perform control procedures each day of testing, 
rather than concurrent with each testing event. We do not know how many 
of these laboratories test patient specimens more than once per day for 
each immunology procedure; therefore, we cannot estimate the cost 
savings if control procedures are performed less frequently. However, 
these provisions for the frequency of control testing do not supercede 
manufacturers' instructions or laboratory specifications that may 
require control testing more frequently; for example, each time patient 
specimens are tested.

Hematology

    For hematology, we are reducing the required frequency for control 
testing from once each 8 hours of operation to once each day of 
testing. There are a total of 32,753 laboratories (Certificate of 
Compliance (16,332), Certificate of Accreditation (15,477), and State-
exempt (944)) that perform hematology testing to which this change may 
apply. We do not know the exact number of laboratories that this change 
will affect because this change will only impact laboratories 
performing testing longer than 8 hours per day. However, we expect it 
will affect most hospital laboratories and many independent 
laboratories, since the majority of hospitals and independent 
laboratories operate 24 hours per day. For these

[[Page 3698]]

laboratories, if manufacturer instructions and laboratory 
specifications allow, performance of two control testing events per day 
can be eliminated for each hematology analyzer. Therefore, the 
aggregate savings may be significant, but we cannot estimate the 
impact.

Alternative Approaches

    For these three changes, the aggregate impact will be a cost 
savings; however, we have insufficient information to estimate the 
reduced burden or savings in reduced analyst time, cost of reagents, 
and control materials associated with the reduced frequency of control 
material testing. We considered leaving the requirements for control 
procedures unchanged; however, based upon the current stability of the 
test systems used in these three areas, we have determined that few 
additional testing errors would be prevented by more frequent control 
testing.
4. Completion of Laboratory Director Phase-in
    We are completing the phase-in qualification requirement for high 
complexity laboratory director that allows individuals with a doctoral 
degree to qualify based on training and experience in lieu of board 
certification. With the implementation of this final rule, board 
certification will be required under one provision. However, under the 
second provision, we are allowing individuals, who qualified under the 
phase-in provision and who have served or are now serving as directors 
of laboratories performing high complexity testing and have at least 2 
years of training or experience, or both, and 2 years of experience 
directing or supervising high complexity testing to continue to serve 
as laboratory directors. To ensure a smooth transition to the new 
provisions for directors of high complexity testing who are not board 
certified (but who have doctoral degrees), we will not be holding 
facilities out of compliance with the provisions of the rule concerning 
directors who are not board certified until the effective date of this 
new rule, to the extent the facilities are otherwise in compliance with 
the requirements for laboratory directors.

Rationale

    Personnel qualifications are considered an essential benchmark of 
performance and requiring appropriate qualifications for the complexity 
level of testing performed by the laboratory is in the best interest of 
quality testing. High complexity testing requires more extensive 
knowledge, training, and experience to perform the management and 
administrative duties necessary to ensure that personnel are competent, 
methodologies are appropriate, and the quality control and quality 
assessment programs are suitable for the testing performed. The high 
complexity laboratory director qualification requirements in this final 
rule balance the quality concerns with the need to ensure continued 
access to high complexity testing.

Methodology

    To determine the impact of these laboratory director qualification 
requirements over time on laboratories performing high complexity 
testing, we estimated the number of high complexity laboratories 
potentially impacted and the number of qualified individuals available 
to serve as high complexity laboratory directors during the next 5 
years.

Laboratory Demographics

    Using the CMS OSCAR (2001) database, we have determined that 
approximately 8,000 of the 22,720 Certificate of Compliance (COC) 
laboratories (35 percent, or 4.7 percent of all CLIA laboratories) 
perform some high complexity testing. To determine the total number of 
Certificate of Accreditation (COA) laboratories that perform high 
complexity testing, we included the approximately 9,200 laboratories 
accredited by five of the CLIA-approved accreditation organizations 
(American Association of Blood Banks, American Osteopathic Association, 
American Society for Histocompatibility and Immunogenetics, College of 
American Pathologists, and Joint Commission on Accreditation of 
Healthcare Organizations). The majority of these laboratories are 
independent or hospital-based and are assumed to perform some high 
complexity testing. We also estimated that approximately 1,700 of the 
6,881 COLA-accredited laboratories (25 percent) perform some high 
complexity testing. In addition, the number of high complexity 
laboratories in the two CLIA-exempt States, New York (540) and 
Washington (235), is approximately 775 laboratories (New York and 
Washington, personal communication, March 2002). Therefore, the total 
number of CLIA laboratories (including New York and Washington) 
performing some high complexity testing in the United States is 
estimated to be approximately 19,700 laboratories.
    As previously mentioned and illustrated at Table 4, the percentages 
of laboratories with each certificate type have remained stable over 
the past several years; however, the absolute numbers show trends 
toward lower complexity levels (waiver and PPM). While we expect this 
trend to continue in the future because of the widening availability of 
waived tests, we assume that COC laboratories switching to waiver and 
PPM certificates are those that perform only moderate complexity 
testing and the number of COC laboratories performing some high 
complexity testing will remain stable. In addition, we assume the 
number of accredited laboratories performing some high complexity 
testing will remain fairly stable, as has been the trend in the past 
several years.

High Complexity Laboratory Director Demographics

    We also used the OSCAR (2001) database to identify the CLIA 
qualification requirements by which those individuals currently serving 
as laboratory directors of COC high complexity laboratories qualified. 
Using this data, we have calculated that 28 percent of these 
laboratories are directed by board-certified pathologists; 56 percent 
by licensed physicians with laboratory training or experience; 5 
percent by individuals with doctoral degrees; 3 percent by individuals 
who have been serving as laboratory directors and were qualified as a 
laboratory director on or before February 28, 1992 (according to the 
March 14, 1990 final rule with comment period (55 FR 9538) published in 
the Federal Register); 7 percent by individuals who on or before 
February 28, 1992 were qualified under State law to direct a laboratory 
in the State in which the laboratory was located; and less than 1 
percent by individuals who meet the qualifications currently at Sec.  
493.1443(b)(6) for the subspecialty of oral pathology.
    We assume individuals currently serving as high complexity 
laboratory directors will retire at approximately the same rate as 
projected for the general population; that is, on average 3.8 percent 
per year for fiscal years 2001 through 2005 (U.S. Office of Personnel 
Management, Central Personnel Data Files, 2000). Therefore, we 
anticipate 3.8 percent of the approximately 19,700 high complexity 
laboratories (750) will need to hire a new laboratory director each 
year for the next 5 years. Pool of Individuals Qualified to Serve as 
High Complexity Laboratory Directors.
    Using data (September 2000) from the American Board of Medical 
Specialties (ABMS), we estimated the total number of physicians that 
have 1 year of

[[Page 3699]]

laboratory training during medical residency to be 17,400. In addition, 
ABMS reports 5,784 pathologists received board certification over the 
past 10 years. This number is consistent with the Accreditation Council 
for Graduate Medical Education's (ACGME) data indicating there are 
approximately 2,660 anatomical and clinical pathology residents 
enrolled through the current academic year (ending June 2002). These 
residents will be eligible for board certification over the next 4 
years.
    The total number of board-certified doctoral-degreed individuals is 
estimated to be 2,090 (American Board of Bioanalysis (ABB), American 
Board of Clinical Chemistry (ABCC), American Board of Forensic 
Toxicology (ABFT), American Board of Medical Genetics (ABMG), American 
Board of Medical Laboratory Immunology (ABMLI), American Board of 
Medical Microbiology (ABMM), and National Registry of Certified 
Chemists (NRCC)). In addition, one HHS-approved board reports an 
average of 8 individuals receiving certification annually, another 
board reports an average of 11 annually, and a third board reports 37 
annually (AAB, ABCC, ABFT, ABMLI, ABMM, NRCC, personal communication, 
March 2002).
    Based on the data provided by the HHS-approved boards, ABMS, and 
ACGME, we believe there will be a sufficient number of individuals 
available to fill the possible 750 high complexity laboratory director 
vacancies per year over the next 5 years. Moreover, only 5 percent of 
the COC high complexity laboratories currently employ a laboratory 
director with a doctoral degree. We believe the percentage of COA and 
Washington State high complexity laboratories employing a laboratory 
director with a doctoral degree may be about the same or lower. 
Therefore, we estimate that approximately 180 of the 958 COC, COA, and 
Washington State high complexity laboratories that employ a doctoral-
degreed individual as a laboratory director may have to replace their 
director during the next 5 years (36 annually). We did not include the 
high complexity laboratories in New York because they require 
laboratory directors to have ``specific'' training or experience in the 
specialty(ies) of testing the laboratory performs.

Benefits

Impact

    There will be no immediate impact because the second provision 
included in this final rule allows individuals who have served or are 
currently serving as laboratory directors and have at least 2 years of 
training or experience, or both, and 2 years of experience directing or 
supervising high complexity testing to continue in their capacity 
without obtaining board certification. This provision circumvents the 
costly and disruptive burdens associated with currently employed 
individuals obtaining board certification and laboratories, which 
perform high complexity testing, replacing currently serving directors.
    With regard to future impact, available data indicate there are 
ample numbers of qualified individuals available to fill the estimated 
annual high complexity laboratory director vacancies over the next 5 
years. In addition, the CLIA regulations permit qualified individuals 
to direct up to five laboratories, which may further lessen the burden 
associated with replacing retiring laboratory directors. However, 
States and accrediting organizations may have more stringent 
qualification requirements for laboratory directors and affected 
laboratories would need to continue to meet these requirements.

Costs

    The provisions in this final rule at Sec.  493.1443(b)(3), will 
have no immediate costs, and we believe the costs over the next 5 years 
will be no greater than the costs laboratories performing high 
complexity testing currently experience when replacing directors.

Alternative Approaches

    In the December 28, 2001 proposed rule, we considered qualifying 
individuals with a doctoral degree and 6 years of laboratory training 
and experience, or both (including 2 years experience directing or 
supervising high complexity testing), as directors of laboratories 
performing high complexity testing. While we offered this as an 
alternative qualification pathway, we agree with the majority of 
commenters and the CLIAC recommendation that the provision is not 
commensurate with the responsibilities of a high complexity laboratory 
director or consistent with the qualification requirements and 
responsibilities specified for the other CLIA laboratory personnel 
categories. Moreover, we have determined that this qualification 
pathway is not needed to ensure a sufficient pool of qualified 
individuals to serve as high complexity laboratory directors and thus 
continued access to high complexity testing.
5. Miscellaneous Changes
    The reorganization of this final rule reflects the flow of 
laboratory testing (from receipt of the specimen through test 
performance, test reporting and systems' assessments), eliminates 
duplicative requirements, and rewords certain requirements. In response 
to comments received to previous rulemakings, wherever possible we have 
made changes to the regulations to reduce the burden and expense to 
laboratories. Also, in recognition of new and emerging technologies and 
methodologies, obsolete requirements have been deleted and a few new 
requirements have been added. Listed below are several of these 
revisions, not yet discussed in this impact analysis, which may result 
in some change in costs or burden for laboratories. While we believe 
the change in costs or burden, or both, will be relatively minor, lack 
of data and information makes these estimates either difficult or 
impossible to quantify.

Revisions Resulting in No Change in Burden and Costs

    The FDA QC review process was intended to be implemented when the 
QC phase-in ended, but we established through our survey process that 
the review would be not be of benefit to laboratories. Because this 
review was not implemented, there is no impact.
    [sbull] Records of test system performance specifications 
established or verified as required under Sec.  493.1253 must be 
retained for the period of time the test system is in use. Because this 
information provides important data about the laboratory's test system 
performance (for example, accuracy, precision, and reportable range of 
patient results) that the laboratory is required (formerly at Sec.  
493.1109(g), now at Sec.  493.1291(e)) to provide to clients upon 
request, laboratories should have already been maintaining this 
information. Therefore, there is no additional burden with this change.
    [sbull] When a laboratory transcribes or enters test requisition or 
authorization information into a record or information system, it must 
ensure that the information is transcribed or entered accurately. 
Formerly at Sec.  493.1701, laboratories were responsible for 
identifying and correcting problems and ensuring accurate, reliable, 
and prompt reporting of test results. Inaccurate transcription of test 
requisition or authorization information would be one example of a 
problem, if left uncorrected, that could interfere with both the 
reporting of test results and the accuracy of the results. For this 
reason, we believe this new requirement should have no impact on the 
laboratory's burden or costs.

[[Page 3700]]

    [sbull] Section 493.1254 now specifies that when using unmodified 
manufacturer's equipment, instrument or test systems, the laboratory 
must follow the manufacturer's instructions for maintenance and 
function check protocols rather than establish its own. While this 
revision results in a less stringent requirement than that specified 
under former Sec.  493.1215, we do not anticipate a change (decrease) 
in burden or costs to the laboratory because following the 
manufacturer's instructions for maintenance and function checks when 
using unmodified equipment, instruments, or test systems was acceptable 
practice for meeting the former requirement.
    [sbull] In the specialty of histocompatibility now at Sec.  
493.1278, the laboratory's reagent typing inventory must indicate 
reagent specificity as well as the previously required source, bleeding 
date and identification number, and volume remaining. Indicating a 
reagent's specificity in the laboratory's reagent inventory is routine 
laboratory practice that was inadvertently not addressed in the 
regulations. This new requirement for documentation of reagent 
specificity will have no impact on the laboratory's burden or costs.

Revisions Resulting in a Decrease in Burden or Costs.

    [sbull] We are eliminating the requirement under the specialty of 
histocompatibility for each individual performing testing to evaluate 
previously tested specimens monthly as specified formerly at Sec.  
493.1265. The mechanism for and frequency of competency assessment of 
histocompatibility testing personnel will now be determined, as it is 
in all other laboratory specialties and subspecialties, by the 
laboratory's technical consultant or supervisor under Sec. Sec.  
493.1413(b)(8) and (9) and 493.1449(b)(8) and (9), respectively. 
Although this is a reduction in burden, we cannot estimate the cost 
savings.
    [sbull] For laboratories performing histocompatibility testing, we 
are eliminating the specified frequencies for screening potential 
transplant recipient sera for performed HLA-A and B antibodies 
(formerly at Sec.  493.1265(a)(8)(i)). Instead, in this final rule at 
Sec.  493.1278(d)(5), we are requiring the laboratory to have available 
and follow a policy, consistent with clinical transplant protocols, for 
the frequency of such antibody screening. While this is most likely a 
reduction in burden, we cannot estimate the cost savings, since 
emerging data and research information will be an ongoing factor in 
determining appropriate screening frequencies.
    [sbull] For the performance of non-renal transplantation in an 
emergency situation, we are eliminating the requirement that the 
results of final crossmatches be available before the transplantation 
when the recipient demonstrates presensitization by prior serum 
screening. In this final rule at Sec.  493.1278(f)(3) (formerly at 
Sec.  493.1265(b)(3)), the laboratory must have available, and follow, 
policies that address when HLA testing and final crossmatches are 
required for presensitized non-renal transplant recipients. We cannot 
estimate the savings from this reduction.

Revisions for Which There May Be a Negligible Increase in Burden or 
Costs

    [sbull] The laboratory must ensure a uni-directional workflow for 
molecular amplification systems that are not contained in enclosed 
systems. This includes maintaining physically separate areas for 
specimen preparation, amplification and product detection and reagent 
preparation, as applicable. This is a recommended guideline for good 
laboratory practice by several laboratory professional organizations. 
Although we are unable to estimate the number of laboratories that 
perform molecular amplification with open systems without following the 
recommended guideline, we expect the number to be small and any 
increase in burden or cost with meeting this new requirement, now at 
Sec.  493.1101, negligible.
    [sbull] If the laboratory ceases operation, it must make provisions 
to ensure that all records, slides, blocks, and tissues are maintained 
for the applicable time frames. We anticipate that this change now at 
Sec.  493.1105 will affect few laboratories; however, we cannot 
estimate the number or associated cost.
    [sbull] In the former requirements at Sec. Sec.  493.911(c)(1), 
493.913(c)(1), 493.915(c)(1), 493.917(c)(1), 493.919(c)(1), 
493.923(b)(1), 493.927(c)(1), 493.931(c)(1), 493.933(c)(1), 
493.937(c)(1), and 493.941(c)(1) PT programs were required to grade PT 
results by first comparing the laboratory's response to the response 
which reflects agreement of either 90 percent of 10 or more referee 
laboratories or 90 percent or more of all participating laboratories. 
If this consensus agreement requirement was met, then the results could 
be graded based on their values relative to the established correct 
response for each PT analyte, subspecialty, or specialty. If the 
consensus requirement was not met, then laboratories were not graded 
and received an acceptable score, by default. As a consequence of this, 
a portion of those laboratories receiving ungraded PT results may have 
failed to recognize that their actual PT performance was not acceptable 
and only realized that their performance was unacceptable when their PT 
results were reviewed as part of an inspection. Thus, in some instances 
laboratories failed to make appropriate corrections to testing 
problems, identified by unacceptable PT performance, in a timely 
manner. Now at Sec. Sec.  493.911(c)(1), 493.913(c)(1), 493.915(c)(1), 
493.917(c)(1), 493.919(c)(1), 493.923(b)(1), 493.927(c)(1), 
493.931(c)(1), 493.933(c)(1), 493.937(c)(1), and 493.941(c)(1), the 
consensus agreement requirement is lowered to 80 percent. Fewer PT 
results will be ungraded and a portion of those laboratories previously 
not graded due to a lack of consensus will receive an unacceptable PT 
grade. Thus, these laboratories will be alerted to potential testing 
problems sooner. Also, with the change at Sec.  493.1236(b)(2), which 
now requires all laboratories to verify testing accuracy for any 
analyte, subspecialty, or specialty assigned a PT score that does not 
reflect the laboratory's actual PT performance, an additional number of 
laboratories may become cognizant of their poor testing performance 
sooner than when PT results are not graded and they receive an 
acceptable score by default. The combination of fewer ungraded PT 
results with the requirement for all laboratories to review and verify 
their PT results, especially when they are deemed questionable by the 
PT program, will result in these laboratories, in a more timely manner, 
identifying and correcting potential sources of error which may not 
have been otherwise detected, thereby increasing overall laboratory 
accuracy. However, there may be some burden for those laboratories that 
are now required to verify testing accuracy but are having no real 
problem with testing. Since verifying testing accuracy whenever there 
is a potential likelihood of error is generally regarded as good 
laboratory practice, and in most instances the laboratory's routine use 
of QC may be used to verify testing accuracy, this should not be 
considered burdensome. Likewise, PT programs may be slightly 
inconvenienced by the need to change their grading algorithms to 
accommodate the 80 percent consensus requirement. However, it is the 
responsibility of PT programs to assist laboratories in assessing their 
testing performance by providing PT samples that can be appropriately 
graded.

[[Page 3701]]

Although these changes may affect laboratories and PT programs, the 
impact is not quantifiable and is considered minor compared to the 
overall beneficial effect of improved laboratory testing accuracy.
    [sbull] Test requisitions or other written or electronic 
authorizations for testing must include the patient's sex and age or 
date of birth as specified now at Sec.  493.1241. We expect a 
negligible increase in burden or cost because the patient's age or date 
of birth was required for Pap smears, formerly at Sec.  493.1105(e), 
and most laboratories are already obtaining the patient's gender, since 
it is frequently necessary for appropriate test interpretation (as 
required formerly at Sec.  493.1105(f)). The number of laboratories 
that have not been requesting the patient's gender and age or date of 
birth is unknown.
    [sbull] The laboratory must use a control system capable of 
detecting reaction inhibition when performing molecular amplification 
procedures in which inhibition is a significant source of false 
negative results. This is a recommended guideline for good laboratory 
practice by several laboratory professional organizations and is now 
specified at Sec.  493.1256(d)(3)(v). While we are unable to estimate 
the incidence of reaction inhibition or number of laboratories 
performing molecular amplification procedures without following the 
recommended guideline, we expect the number to be small and any 
increase in burden and/or cost with meeting this new requirement 
negligible.
    [sbull] The laboratory must check immunohistochemical stains for 
positive and negative reactivity each time of use. Although this is an 
increase from the requirement (formerly at Sec.  493.1259, now at Sec.  
493.1273(a)) to check special stains for positive reactivity, we cannot 
estimate the laboratory impact because we do not know the number of 
laboratories that perform immunohistochemical stains or how often the 
staining is performed. We expect this change to affect a small number 
of laboratories, and the increase in burden and costs will be small.
    [sbull] In the specialty of clinical cytogenetics, sex 
determination must be performed by full chromosome analysis. Formerly, 
in clinical cytogenetics at Sec.  493.1267(a) (now at Sec.  
493.1276(c)), full chromosome analysis was only required as a 
confirmatory test when the laboratory obtained atypical results on X 
and Y chromatin counts. Several commenters stated that due to the 
frequency of mosaicism in individuals with sex chromosome anueploidy, 
Barr body and ``Y'' body analysis is no longer considered the standard 
of practice for sex determination and should be eliminated from the 
cytogenetics laboratory test menu. Several laboratory professional 
organizations consider sex determination by full chromosome analysis 
the standard for good laboratory practice; therefore, we added this 
requirement. Although we are unable to estimate the number of 
cytogenetics laboratories that perform sex determination other than by 
full chromosome analysis, we expect the number to be small and any 
increase in burden or cost with meeting this requirement negligible.
    [sbull] The requirements for the test report (formerly at Sec.  
493.1109, now at Sec.  493.1291) must include the patient's name and 
identification number, or unique patient identifier and identification 
number; the test report date; and if appropriate, the specimen source. 
These are standard practices in most laboratories and the impact on 
burden or cost is expected to be minor.
    In accordance with Executive Order 12866, this regulation was 
reviewed by the Office of Management and Budget.

References

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all programs for a specific academic year Ending June 30, 2002.'' 
<http://www.acgame.org/adspublic/reports/ accredited--programs--
all.asp. (April 23, 2002).
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Questionnaire (Appendices 1 and 2) 1996. Unpublished data.
American Association for Clinical Chemistry. ``Quality Assurance 
Alternatives for POCT.'' Audioconference, February 4, 1999.
American Board of Medical Specialties. ``General Certificates Issued 
1991-2001, Table 2.'' September 2000. <http://www.abms.org/statistics.asp (April 16, 2002).
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Diplomats by Speciality Certificate.'' September 2002. <http://www.abms.org/statistics.asp (April 16, 2002).
American Medical Association, Center for Health Policy Research, 
``Physician socioeconomic statistics,'' 2000-2002 edition, 2001.
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McCurdy to the Clinical Laboratory Improvement Advisory Committee, 
September 25, 1996.
American Society for Microbiology. ``ASM benchmarking survey, 
microbiology productivity ``99.'' Report by Roberta Carey to the 
Clinical Laboratory Improvement Advisory Committee, September 22, 
1999.
Astles, John R., Harvey B. Lipman, William O. Schalla, Sharon O. 
Blummer, Ronald F. Feld, Charlene Smith, Thomas L. Hearn. ``Impact 
of quality control on accuracy in enzyme immunoassay testing for 
human immunodeficiency virus type 1 antibodies.'' Archives of 
Pathology and Laboratory Medicine 122, 8 (1998), pp. 700-707.
Burman, William J., B.L. Stone, Randall R. Reves, et al. ``The 
incidence of false-positive cultures for Mycobacterium 
tuberculosis.'' American Journal of Respiratory and Critical Care 
Medicine, 155,1 (1997): pp. 321-326.
Bureau of Labor Statistics. Occupational Outlook Handbook, 2000-2001 
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Centers for Disease Control and Prevention. Laboratory practices for 
diagnosis of tuberculosis--United States, 1994. Morbidity and 
Mortality Weekly Report 1995, 44:587-590.
Eisenberg, Henry D., Ed. Essential Procedures for Clinical 
Microbiology (Chapter 4.8 Mycobacteriology--Identification 
Procedures from Culture, pp. 195-196), ASM Press, Washington, D.C., 
(1998).
Hoerger Thomas J., Jennifer L. Eggleston, Richard C. Lindrooth, and 
Emek Basker. ``Background report on the clinical laboratory 
industry. Final report.'' June 1997. Prepared by Centers for 
Economic Research, Research Triangle Institute, Research Triangle 
Institute, NC.
Huebner, Robin E., Robert C. Good, and Jerome I. Tokars. ``Current 
practices in mycobacteriology: results of a survey of state public 
health laboratories.'' Journal of Clinical Microbiology 31, 4 
(1993), pp. 771-775.
Institute of Medicine (IOM), Committee on Medicare Payment 
Methodology for Clinical Laboratory Services. (2000). Medical 
Laboratory Payment Policies, Now and in the Future (Appendix D). 
Washington, DC: National Academy Press.
LaBeau, Kathleen M, Marianne Simon and Steven J. Steindel. ``The 
Pacific Northwest Laboratory Medicine Sentinel Monitoring Network.'' 
Final Report of the Findings of Questionnaire II, Test Volume and 
Menu Changes: 1997-1999.'' July 1999.
NCCLS Guideline EP 6-P. Evaluation of the linearity of quantitative 
analytical methods; proposed guideline. (1999). Villanova, PA: 
NCCLS.
NCCLS Document EP 15-P. User demonstration of performance for 
precision and accuracy; proposed guideline. (1998). Villanova, PA: 
NCCLS.
NCCLS Document C 28-A. How to define and determine reference 
intervals in the clinical laboratory; approved guideline. (1995). 
Villanova, PA: NCCLS.
Online Survey and Certification Reporting System (OSCAR). 
(Electronic database). (2001). Baltimore, MD: Centers for Medicare & 
Medicaid Services. (Producer and Distributor).
Steindel, Stephen J., William J. Rauch, Marianne K. Simon, and James 
Handsfield. ``National Inventory of Clinical Testing Services 
(NICLTS): development and test distribution for 1996.'' Archives of 
Pathology and Laboratory Medicine 124, (2000), pp. 1201-1208.
Tershakovec, Andrew M., S. Diane Brannon, Michael J. Bennett, and 
Barbara M. Shannon. ``The cost of implementation of

[[Page 3702]]

the Clinical Laboratory Improvement Amendments of 1988--the example 
of pediatric office-based cholesterol screening.'' Pediatrics 96, 2 
(1995), pp. 230-234.
Ward-Cook, K., and Suzanne Tannar. ``2000 wage and vacancy survey of 
medical laboratories.'' Laboratory Medicine 32, 3, (2001), pp.124-
138.
U.S. Government, Office of Personnel Management, Central Personnel 
Data File. ``Retirement Projections, Fiscal Years 2001-2005.'' 
http://www.opm.gov/feddata/retire/rs-projections.pdf. (April 16, 
2002).

List of Subjects in 42 FR Part 493

    Grant programs--health, Health facilities, Incorporation by 
Reference, Laboratories, Medicaid, Medicare, Reporting and 
recordkeeping requirements.

    For the reasons set forth in the preamble, the Centers for Medicare 
& Medicaid Services is amending 42 CFR Chapter IV part 493 as set forth 
below:

PART 493--LABORATORY REQUIREMENTS

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

    Authority: Sec. 353 of the Public Health Service Act, secs. 
1102, 1861(e), the sentence following sections 1861(s)(11) through 
1861(s)(16) of the Social Security Act (42 U.S.C. 263a, 1302, 
1395x(e), and the sentence following 1395x(s)(11) through 
1395x(s)(16)).

Subpart A--General Provisions

    2. In Sec.  493.2, the introductory text is republished, and the 
following definitions are added in alphabetical order to read as 
follows:


Sec.  493.2  Definitions

    As used in this part, unless the context indicates otherwise--
* * * * *
    Calibration means a process of testing and adjusting an instrument 
or test system to establish a correlation between the measurement 
response and the concentration or amount of the substance that is being 
measured by the test procedure.
    Calibration verification means the assaying of materials of known 
concentration in the same manner as patient samples to substantiate the 
instrument or test system's calibration throughout the reportable range 
for patient test results.
* * * * *
    FDA-cleared or approved test system means a test system cleared or 
approved by the FDA through the premarket notification (510(k)) or 
premarket approval (PMA) process for in-vitro diagnostic use. Unless 
otherwise stated, this includes test systems exempt from FDA premarket 
clearance or approval.
* * * * *
    Reportable range means the span of test result values over which 
the laboratory can establish or verify the accuracy of the instrument 
or test system measurement response.
* * * * *
    Test system means the instructions and all of the instrumentation, 
equipment, reagents, and supplies needed to perform an assay or 
examination and generate test results.
* * * * *


Sec.  493.3  [Amended]

    3. Amend Sec.  493.3, as follows:
    a. In paragraph(b)(3), remove the words ``National Institutes on 
Drug Abuse (NIDA)'' and add, in their place, the words ``Substance 
Abuse and Mental Health Services Administration (SAMHSA)''.
    b. In paragraph (b)(3), remove the word ``NIDA'' and add, in its 
place, the word ``SAMHSA''.


Sec.  493.20  [Amended]

    3a. Amend Sec.  493.20, as follows:
    a. In paragraph (b), remove the reference to ``subpart P''.
    b. In paragraph (b), remove the cross reference to ``Sec.  
493.1777'' and add, in its place ``Sec. Sec.  493.1773 and 493.1777''.
    c. In paragraph (c), remove the cross reference to ``Sec. Sec.  
493.15(e) and 493.1775'' and add, in its place, ``Sec. Sec.  493.15(e), 
493.1773, and 493.1775''.


Sec.  493.25  [Amended]

    4. Amend Sec.  493.25 as follows:
    a. In paragraph (b), remove the reference to ``subpart P''.
    b. In paragraph (c), remove the reference to ``subpart
    P''.
    c. In paragraph (c), remove ``Sec.  493.1777'' and add, in its 
place, ``Sec. Sec.  493.1773 and 493.1777''.
    d. In paragraph (d), remove the reference to ``subpart P''.
    e. In paragraph (d), remove the cross reference to ``Sec. Sec.  
493.15(e) and 493.1775'' and add, in its place, ``Sec. Sec.  493.15(e), 
493.1773, and 493.1775''.

Subpart C--Registration Certificate, Certificate for Provider-
Performed Microscopy Procedures, and Certificate of Compliance


Sec.  493.43  [Amended]

    6. In Sec.  493.43(a), remove the words ``tests of moderate 
complexity (including the subcategory) or high complexity, or any 
combination of these tests,'' and add, in their place, the words 
``nonwaived testing''.


Sec.  493.45  [Amended]

    7. In Sec.  493.45(c)(3), remove the reference to ``subpart P''.


Sec.  493.47  [Amended]

    8. Amend Sec.  493.47 as follows:
    a. In paragraph (c)(2), remove the reference to ``subpart P''.
    b. In paragraph (c)(3), remove the cross reference to ``Sec.  
493.1776'' and add, in its place, ``Sec. Sec.  493.1773 and 493.1775''.


Sec.  493.49  [Amended]

    9. In Sec.  493.49(a)(3), remove the reference to ``subpart P''.

Subpart F--General Administration


Sec.  493.643  [Amended]

    10. In Sec.  493.643(c)(3)(ix), add the word ``Clinical'' before 
the word ``Cytogenetics''.

Subpart H--Participation in Proficiency Testing for Laboratories 
Performing Nonwaived Testing

    11. Revise the heading of Subpart H to read as set forth above.


Sec.  493.801  [Amended]

    12. In Sec.  493.801(a)(2)(ii), remove the cross reference to 
``Sec.  493.1709'' and add, in its place, ``Sec.  493.1236(c)(1)''.


Sec.  493.803  [Amended]

    13. In Sec.  493.803(a), remove the words ``tests of moderate 
complexity (including the subcategory) and/or high complexity'' and 
add, in their place, the words ``nonwaived testing''.


Sec.  493.807  [Amended]

    14. Revise the heading of Sec. 493.807 to read as follows:


Sec.  493.807  Condition: Reinstatement of laboratories performing 
nonwaived testing.

Subpart I--Proficiency Testing Programs for Nonwaived Testing

    15. Revise the heading of subpart I to read as set forth above.


Sec. Sec.  493.911, 493.913, 493.915, 493.917, 493.919, 493.923, 
493.927, 493.931, 493.933, 493.937, and 493.941  [Amended]

    16. In Sec. Sec.  493.911(c)(1), 493.913(c)(1), 493.915(c)(1), 
493.917(c)(1), 493.919(c)(1), 493.923(b)(1), 493.927(c)(1), 
493.931(c)(1), 493.933(c)(1), 493.937(c)(1), and 493.941(c)(1), remove 
``90 percent'' and add, in its place, ``80 percent'' wherever it 
appears.


Sec.  493.945  [Amended]

    17. In Sec.  493.945(a)(1), remove ``Sec.  493.1257'' and add, in 
its place,

[[Page 3703]]

``Sec. Sec.  493.1105(a)(7)(i)(A) and 493.1274(f)(2)''.

    18. Subpart J, consisting of Sec. Sec.  493.1100 through 493.1105, 
and subpart K, consisting of Sec. Sec.  493.1200 through 493.1299, are 
revised to read as follows:
Subpart J--Facility Administration for Nonwaived Testing
Sec.
493.1100 Condition: Facility administration.
493.1101 Standard: Facilities.
493.1103 Standard: Requirements for transfusion services.
493.1105 Standard: Retention requirements.
Subpart K--Quality Systems for Nonwaived Testing
493.1200 Introduction.
493.1201 Condition: Bacteriology.
493.1202 Condition: Mycobacteriology.
493.1203 Condition: Mycology.
493.1204 Condition: Parasitology.
493.1205 Condition: Virology.
493.1207 Condition: Syphilis serology.
493.1208 Condition: General immunology.
493.1210 Condition: Routine chemistry.
493.1211 Condition: Urinalysis.
493.1212 Condition: Endocrinology.
493.1213 Condition: Toxicology.
493.1215 Condition: Hematology.
493.1217 Condition: Immunohematology.
493.1219 Condition: Histopathology.
493.1220 Condition: Oral pathology.
493.1221 Condition: Cytology.
493.1125 Condition: Clinical cytogenetics.
493.1226 Condition: Radiobioassay.
493.1227 Condition: Histocompatibility.

General Laboratory Systems

493.1230 Condition: General laboratory systems.
493.1231 Standard: Confidentiality of patient information.
493.1232 Standard: Specimen identification and integrity.
493.1233 Standard: Complaint investigations.
493.1234 Standard: Communications.
493.1235 Standard: Personnel competency assessment policies.
493.1236 Standard: Evaluation of proficiency testing performance.
493.1239 Standard: General laboratory systems assessment.

Preanalytic Systems

493.1240 Condition: Preanalytic systems.
493.1241 Standard: Test request.
493.1242 Standard: Specimen submission, handling, and referral.
493.1249 Standard: Preanalytic systems assessment.

Analytic Systems

493.1250 Condition: Analytic systems.
493.1251 Standard: Procedure manual.
493.1252 Standard: Test systems, equipment, instruments, reagents, 
materials, and supplies.
493.1253 Standard: Establishment and verification of performance 
specifications.
493.1254 Standard: Maintenance and function checks.
493.1255 Standard: Calibration and calibration verification 
procedures.
493.1256 Standard: Control procedures.
493.1261 Standard: Bacteriology.
493.1262 Standard: Mycobacteriology.
493.1263 Standard: Mycology.
493.1264 Standard: Parasitology.
493.1265 Standard: Virology.
493.1267 Standard: Routine chemistry.
493.1269 Standard: Hematology.
493.1271 Standard: Immunohematology.
493.1273 Standard: Histopathology.
493.1274 Standard: Cytology.
493.1276 Standard: Clinical cytogenetics.
493.1278 Standard: Histocompatibility.
493.1281 Standard: Comparison of test results.
493.1282 Standard: Corrective actions.
493.1283 Standard: Test records.
493.1189 Standard: Analytic systems assessment.

Postanalytic Systems

493.1290 Condition: Postanalytic systems.
493.1291 Standard: Test report.
493.1299 Standard: Postanalytic systems assessment.

Subpart J--Facility Administration for Nonwaived Testing


Sec.  493.1100  Condition: Facility administration.

    Each laboratory that performs nonwaived testing must meet the 
applicable requirements under Sec. Sec.  493.1101 through 493.1105, 
unless HHS approves a procedure that provides equivalent quality 
testing as specified in Appendix C of the State Operations Manual (CMS 
Pub. 7).


Sec.  493.1101  Standard: Facilities.

    (a) The laboratory must be constructed, arranged, and maintained to 
ensure the following:
    (1) The space, ventilation, and utilities necessary for conducting 
all phases of the testing process.
    (2) Contamination of patient specimens, equipment, instruments, 
reagents, materials, and supplies is minimized.
    (3) Molecular amplification procedures that are not contained in 
closed systems have a uni-directional workflow. This must include 
separate areas for specimen preparation, amplification and product 
detection, and, as applicable, reagent preparation.
    (b) The laboratory must have appropriate and sufficient equipment, 
instruments, reagents, materials, and supplies for the type and volume 
of testing it performs.
    (c) The laboratory must be in compliance with applicable Federal, 
State, and local laboratory requirements.
    (d) Safety procedures must be established, accessible, and observed 
to ensure protection from physical, chemical, biochemical, and 
electrical hazards, and biohazardous materials.
    (e) Records and, as applicable, slides, blocks, and tissues must be 
maintained and stored under conditions that ensure proper preservation.


Sec.  493.1103  Standard: Requirements for transfusion services.

    A facility that provides transfusion services must meet all of the 
requirements of this section and document all transfusion-related 
activities.
    (a) Arrangement for services. The facility must have a transfusion 
service agreement reviewed and approved by the responsible party(ies) 
that govern the procurement, transfer, and availability of blood and 
blood products.
    (b) Provision of testing. The facility must provide prompt ABO 
grouping, D(Rho) typing, unexpected antibody detection, compatibility 
testing, and laboratory investigation of transfusion reactions on a 
continuous basis through a CLIA-certified laboratory or a laboratory 
meeting equivalent requirements as determined by CMS.
    (c) Blood and blood products storage and distribution. (1) If a 
facility stores or maintains blood or blood products for transfusion 
outside of a monitored refrigerator, the facility must ensure the 
storage conditions, including temperature, are appropriate to prevent 
deterioration of the blood or blood product.
    (2) The facility must establish and follow policies to ensure 
positive identification of a blood or blood product recipient.
    (d) Investigation of transfusion reactions. The facility must have 
procedures for preventing transfusion reactions and when necessary, 
promptly identify, investigate, and report blood and blood product 
transfusion reactions to the laboratory and, as appropriate, to Federal 
and State authorities.


Sec.  493.1105  Standard: Retention requirements.

    (a) The laboratory must retain its records and, as applicable, 
slides, blocks, and tissues as follows:
    (1) Test requisitions and authorizations. Retain records of test 
requisitions and test authorizations, including the patient's chart or 
medical record if used as the test requisition or authorization, for at 
least 2 years.
    (2) Test procedures. Retain a copy of each test procedure for at 
least 2 years after a procedure has been discontinued. Each test 
procedure must include the dates of initial use and discontinuance.

[[Page 3704]]

    (3) Analytic systems records. Retain quality control and patient 
test records (including instrument printouts, if applicable) and all 
analytic systems activities specified in Sec. Sec.  493.1252 through 
493.1289 for at least 2 years. In addition, retain the following:
    (i) Records of test system performance specifications that the 
laboratory establishes or verifies under Sec.  493.1253 for the period 
of time the laboratory uses the test system but no less than 2 years.
    (ii) Immunohematology records, blood and blood product records, and 
transfusion records as specified in 21 CFR 606.160(b)(3)(ii), 
(b)(3)(v), and (d).
    (4) Proficiency testing records. Retain all proficiency testing 
records for at least 2 years.
    (5) Laboratory quality systems assessment records. Retain all 
laboratory quality systems assessment records for at least 2 years.
    (6) Test reports. Retain or be able to retrieve a copy of the 
original report (including final, preliminary, and corrected reports) 
at least 2 years after the date of reporting. In addition, retain the 
following:
    (i) Immunohematology reports as specified in 21 CFR 
606.160(b)(3)(ii), (b)(3)(iv), and (d).
    (ii) Pathology test reports for at least 10 years after the date of 
reporting.
    (7) Slide, block, and tissue retention--
    (i) Slides.
    (A) Retain cytology slide preparations for at least 5 years from 
the date of examination (see Sec.  493.1274(f) for proficiency testing 
exception).
    (B) Retain histopathology slides for at least 10 years from the 
date of examination.
    (ii) Blocks. Retain pathology specimen blocks for at least 2 years 
from the date of examination.
    (iii) Tissue. Preserve remnants of tissue for pathology examination 
until a diagnosis is made on the specimen.
    (b) If the laboratory ceases operation, the laboratory must make 
provisions to ensure that all records and, as applicable, slides, 
blocks, and tissue are maintained and available for the time frames 
specified in this section.

Subpart K--Quality Systems for Nonwaived Testing


Sec.  493.1200  Introduction.

    (a) Each laboratory that performs nonwaived testing must establish 
and maintain written policies and procedures that implement and monitor 
quality systems for all phases of the total testing process (that is, 
preanalytic, analytic, and postanalytic) as well as general laboratory 
systems.
    (b) Each of the laboratory's quality systems must include an 
assessment component that ensures continuous improvement of the 
laboratory's performance and services through ongoing monitoring that 
identifies, evaluates and resolves problems.
    (c) The various components of the laboratory's quality systems are 
used to meet the requirements in this part and must be appropriate for 
the specialties and subspecialties of testing the laboratory performs, 
services it offers, and clients it serves.


Sec.  493.1201  Condition: Bacteriology.

    If the laboratory provides services in the subspecialty of 
Bacteriology, the laboratory must meet the requirements specified in 
Sec. Sec.  493.1230 through 493.1256, Sec.  493.1261, and Sec. Sec.  
493.1281 through 493.1299.


Sec.  493.1202  Condition: Mycobacteriology.

    If the laboratory provides services in the subspecialty of 
Mycobacteriology, the laboratory must meet the requirements specified 
in Sec. Sec.  493.1230 through 493.1256, Sec.  493.1262, and Sec. Sec.  
493.1281 through 493.1299.


Sec.  493.1203  Condition: Mycology.

    If the laboratory provides services in the subspecialty of 
Mycology, the laboratory must meet the requirements specified in 
Sec. Sec.  493.1230 through 493.1256, Sec.  493.1263, and Sec. Sec.  
493.1281 through 493.1299.


Sec.  493.1204  Condition: Parasitology.

    If the laboratory provides services in the subspecialty of 
Parasitology, the laboratory must meet the requirements specified in 
Sec. Sec.  493.1230 through 493.1256, Sec.  493.1264, and Sec. Sec.  
493.1281 through 493.1299.


Sec.  493.1205  Condition: Virology.

    If the laboratory provides services in the subspecialty of 
Virology, the laboratory must meet the requirements specified in 
Sec. Sec.  493.1230 through 493.1256, Sec.  493.1265, and Sec. Sec.  
493.1281 through 493.1299.


Sec.  493.1207  Condition: Syphilis serology.

    If the laboratory provides services in the subspecialty of Syphilis 
serology, the laboratory must meet the requirements specified in 
Sec. Sec.  493.1230 through 493.1256, and Sec. Sec.  493.1281 through 
493.1299.


Sec.  493.1208  Condition: General immunology.

    If the laboratory provides services in the subspecialty of General 
immunology, the laboratory must meet the requirements specified in 
Sec. Sec.  493.1230 through 493.1256, and Sec. Sec.  93.1281 through 
493.1299.


Sec.  493.1210  Condition: Routine chemistry.

    If the laboratory provides services in the subspecialty of Routine 
chemistry, the laboratory must meet the requirements specified in 
Sec. Sec.  493.1230 through 493.1256, Sec.  493.1267, and Sec. Sec.  
493.1281 through 493.1299.


Sec.  493.1211  Condition: Urinalysis.

    If the laboratory provides services in the subspecialty of 
Urinalysis, the laboratory must meet the requirements specified in 
Sec. Sec.  493.1230 through 493.1256, and Sec. Sec.  493.1281 through 
493.1299.


Sec.  493.1212  Condition: Endocrinology.

    If the laboratory provides services in the subspecialty of 
Endocrinology, the laboratory must meet the requirements specified in 
Sec. Sec.  493.1230 through 493.1256, and Sec. Sec.  493.1281 through 
493.1299.


Sec.  493.1213  Condition: Toxicology.

    If the laboratory provides services in the subspecialty of 
Toxicology, the laboratory must meet the requirements specified in 
Sec. Sec.  493.1230 through 493.1256, and Sec. Sec.  493.1281 through 
493.1299.


Sec.  493.1215  Condition: Hematology.

    If the laboratory provides services in the specialty of Hematology, 
the laboratory must meet the requirements specified in Sec. Sec.  
493.1230 through 493.1256, Sec.  493.1269, and Sec. Sec.  493.1281 
through 493.1299.


Sec.  493.1217  Condition: Immunohematology.

    If the laboratory provides services in the specialty of 
Immunohematology, the laboratory must meet the requirements specified 
in Sec. Sec.  493.1230 through 493.1256, Sec.  493.1271, and Sec. Sec.  
493.1281 through 493.1299.


Sec.  493.1219  Condition: Histopathology.

    If the laboratory provides services in the subspecialty of 
Histopathology, the laboratory must meet the requirements specified in 
Sec. Sec.  493.1230 through 493.1256, Sec.  493.1273, and Sec. Sec.  
493.1281 through 493.1299.


Sec.  493.1220  Condition: Oral pathology.

    If the laboratory provides services in the subspecialty of Oral 
pathology, the laboratory must meet the requirements specified in 
Sec. Sec.  493.1230 through 493.1256, and Sec. Sec.  493.1281 through 
493.1299.


Sec.  493.1221  Condition: Cytology.

    If the laboratory provides services in the subspecialty of 
Cytology, the

[[Page 3705]]

laboratory must meet the requirements specified in Sec. Sec.  493.1230 
through 493.1256, Sec.  493.1274, and Sec. Sec.  493.1281 through 
493.1299.


Sec.  493.1225  Condition: Clinical cytogenetics.

    If the laboratory provides services in the specialty of Clinical 
cytogenetics, the laboratory must meet the requirements specified in 
Sec. Sec.  493.1230 through 493.1256, Sec.  493.1276, and Sec. Sec.  
493.1281 through 493.1299.


Sec.  493.1226  Condition: Radiobioassay.

    If the laboratory provides services in the specialty of 
Radiobioassay, the laboratory must meet the requirements specified in 
Sec. Sec.  493.1230 through 493.1256, and Sec. Sec.  493.1281 through 
493.1299.


Sec.  493.1227  Condition: Histocompatibility.

    If the laboratory provides services in the specialty of 
Histocompatibility, the laboratory must meet the requirements specified 
in Sec. Sec.  493.1230 through 493.1256, Sec.  493.1278, and Sec. Sec.  
493.1281 through 493.1299.

General Laboratory Systems


Sec.  493.1230  Condition: General laboratory systems.

    Each laboratory that performs nonwaived testing must meet the 
applicable general laboratory systems requirements in Sec. Sec.  
493.1231 through 493.1236, unless HHS approves a procedure, specified 
in Appendix C of the State Operations Manual (CMS Pub. 7), that 
provides equivalent quality testing. The laboratory must monitor and 
evaluate the overall quality of the general laboratory systems and 
correct identified problems as specified in Sec.  493.1239 for each 
specialty and subspecialty of testing performed.


Sec.  493.1231  Standard: Confidentiality of patient information.

    The laboratory must ensure confidentiality of patient information 
throughout all phases of the total testing process that are under the 
laboratory's control.


Sec.  493.1232  Standard: Specimen identification and integrity.

    The laboratory must establish and follow written policies and 
procedures that ensure positive identification and optimum integrity of 
a patient's specimen from the time of collection or receipt of the 
specimen through completion of testing and reporting of results.


Sec.  493.1233  Standard: Complaint investigations.

    The laboratory must have a system in place to ensure that it 
documents all complaints and problems reported to the laboratory. The 
laboratory must conduct investigations of complaints, when appropriate.


Sec.  493.1234  Standard: Communications.

    The laboratory must have a system in place to identify and document 
problems that occur as a result of a breakdown in communication between 
the laboratory and an authorized individual who orders or receives test 
results.


Sec.  493.1235  Standard: Personnel competency assessment policies.

    As specified in the personnel requirements in subpart M, the 
laboratory must establish and follow written policies and procedures to 
assess employee and, if applicable, consultant competency.


Sec.  493.1236  Standard: Evaluation of proficiency testing 
performance.

    (a) The laboratory must review and evaluate the results obtained on 
proficiency testing performed as specified in subpart H of this part.
    (b) The laboratory must verify the accuracy of the following:
    (1) Any analyte or subspecialty without analytes listed in subpart 
I of this part that is not evaluated or scored by a CMS-approved 
proficiency testing program.
    (2) Any analyte, specialty or subspecialty assigned a proficiency 
testing score that does not reflect laboratory test performance (that 
is, when the proficiency testing program does not obtain the agreement 
required for scoring as specified in subpart I of this part, or the 
laboratory receives a zero score for nonparticipation, or late return 
of results).
    (c) At least twice annually, the laboratory must verify the 
accuracy of the following:
    (1) Any test or procedure it performs that is not included in 
subpart I of this part.
    (2) Any test or procedure listed in subpart I of this part for 
which compatible proficiency testing samples are not offered by a CMS-
approved proficiency testing program.
    (d) All proficiency testing evaluation and verification activities 
must be documented.


Sec.  493.1239  Standard: General laboratory systems assessment.

    (a) The laboratory must establish and follow written policies and 
procedures for an ongoing mechanism to monitor, assess, and, when 
indicated, correct problems identified in the general laboratory system 
requirements specified at Sec. Sec.  493.1231 through 493.1236.
    (b) The general laboratory systems assessment must include a review 
of the effectiveness of corrective actions taken to resolve problems, 
revision of policies and procedures necessary to prevent recurrence of 
problems, and discussion of general laboratory systems assessment 
reviews with appropriate staff.
    (c) The laboratory must document all general laboratory systems 
assessment activities.

Preanalytic Systems


Sec.  493.1240  Condition: Preanalytic systems.

    Each laboratory that performs nonwaived testing must meet the 
applicable preanalytic system(s) requirements in Sec. Sec.  493.1241 
and 493.1242, unless HHS approves a procedure, specified in Appendix C 
of the State Operations Manual (CMS Pub. 7), that provides equivalent 
quality testing. The laboratory must monitor and evaluate the overall 
quality of the preanalytic systems and correct identified problems as 
specified in Sec.  493.1249 for each specialty and subspecialty of 
testing performed.


Sec.  493.1241  Standard: Test request.

    (a) The laboratory must have a written or electronic request for 
patient testing from an authorized person.
    (b) The laboratory may accept oral requests for laboratory tests if 
it solicits a written or electronic authorization within 30 days of the 
oral request and maintains the authorization or documentation of its 
efforts to obtain the authorization.
    (c) The laboratory must ensure the test requisition solicits the 
following information:
    (1) The name and address or other suitable identifiers of the 
authorized person requesting the test and, if appropriate, the 
individual responsible for using the test results, or the name and 
address of the laboratory submitting the specimen, including, as 
applicable, a contact person to enable the reporting of imminently life 
threatening laboratory results or panic or alert values.
    (2) The patient's name or unique patient identifier.
    (3) The sex and age or date of birth of the patient.
    (4) The test(s) to be performed.
    (5) The source of the specimen, when appropriate.

[[Page 3706]]

    (6) The date and, if appropriate, time of specimen collection.
    (7) For Pap smears, the patient's last menstrual period, and 
indication of whether the patient had a previous abnormal report, 
treatment, or biopsy.
    (8) Any additional information relevant and necessary for a 
specific test to ensure accurate and timely testing and reporting of 
results, including interpretation, if applicable.
    (d) The patient's chart or medical record may be used as the test 
requisition or authorization but must be available to the laboratory at 
the time of testing and available to CMS or a CMS agent upon request.
    (e) If the laboratory transcribes or enters test requisition or 
authorization information into a record system or a laboratory 
information system, the laboratory must ensure the information is 
transcribed or entered accurately.


Sec.  493.1242  Standard: Specimen submission, handling, and referral.

    (a) The laboratory must establish and follow written policies and 
procedures for each of the following, if applicable:
    (1) Patient preparation.
    (2) Specimen collection.
    (3) Specimen labeling, including patient name or unique patient 
identifier and, when appropriate, specimen source.
    (4) Specimen storage and preservation.
    (5) Conditions for specimen transportation.
    (6) Specimen processing.
    (7) Specimen acceptability and rejection.
    (8) Specimen referral.
    (b) The laboratory must document the date and time it receives a 
specimen.
    (c) The laboratory must refer a specimen for testing only to a 
CLIA-certified laboratory or a laboratory meeting equivalent 
requirements as determined by CMS.
    (d) If the laboratory accepts a referral specimen, written 
instructions must be available to the laboratory's clients and must 
include, as appropriate, the information specified in paragraphs (a)(1) 
through (a)(7) of this section.


Sec.  493.1249  Standard: Preanalytic systems assessment.

    (a) The laboratory must establish and follow written policies and 
procedures for an ongoing mechanism to monitor, assess, and when 
indicated, correct problems identified in the preanalytic systems 
specified at Sec. Sec.  493.1241 through 493.1242.
    (b) The preanalytic systems assessment must include a review of the 
effectiveness of corrective actions taken to resolve problems, revision 
of policies and procedures necessary to prevent recurrence of problems, 
and discussion of preanalytic systems assessment reviews with 
appropriate staff.
    (c) The laboratory must document all preanalytic systems assessment 
activities.

Analytic Systems


Sec.  493.1250  Condition: Analytic systems.

    Each laboratory that performs nonwaived testing must meet the 
applicable analytic systems requirements in Sec. Sec.  493.1251 through 
493.1283, unless HHS approves a procedure, specified in Appendix C of 
the State Operations Manual (CMS Pub. 7), that provides equivalent 
quality testing. The laboratory must monitor and evaluate the overall 
quality of the analytic systems and correct identified problems as 
specified in Sec.  493.1289 for each specialty and subspecialty of 
testing performed.


Sec.  493.1251  Standard: Procedure manual.

    (a) A written procedure manual for all tests, assays, and 
examinations performed by the laboratory must be available to, and 
followed by, laboratory personnel. Textbooks may supplement but not 
replace the laboratory's written procedures for testing or examining 
specimens.
    (b) The procedure manual must include the following when applicable 
to the test procedure:
    (1) Requirements for patient preparation; specimen collection, 
labeling, storage, preservation, transportation, processing, and 
referral; and criteria for specimen acceptability and rejection as 
described in Sec.  493.1242.
    (2) Microscopic examination, including the detection of 
inadequately prepared slides.
    (3) Step-by-step performance of the procedure, including test 
calculations and interpretation of results.
    (4) Preparation of slides, solutions, calibrators, controls, 
reagents, stains, and other materials used in testing.
    (5) Calibration and calibration verification procedures.
    (6) The reportable range for test results for the test system as 
established or verified in Sec.  493.1253.
    (7) Control procedures.
    (8) Corrective action to take when calibration or control results 
fail to meet the laboratory's criteria for acceptability.
    (9) Limitations in the test methodology, including interfering 
substances.
    (10) Reference intervals (normal values).
    (11) Imminently life-threatening test results or panic or alert 
values.
    (12) Pertinent literature references.
    (13) The laboratory's system for entering results in the patient 
record and reporting patient results including, when appropriate, the 
protocol for reporting imminent life threatening results, or panic, or 
alert values.
    (14) Description of the course of action to take if a test system 
becomes inoperable.
    (c) Manufacturer's test system instructions or operator manuals may 
be used, when applicable, to meet the requirements of paragraphs (b)(1) 
through (b)(12) of this section. Any of the items under paragraphs 
(b)(1) through (b)(12) of this section not provided by the manufacturer 
must be provided by the laboratory.
    (d) Procedures and changes in procedures must be approved, signed, 
and dated by the current laboratory director before use.
    (e) The laboratory must maintain a copy of each procedure with the 
dates of initial use and discontinuance as described in Sec.  
493.1105(a)(2).


Sec.  493.1252  Standard: Test systems, equipment, instruments, 
reagents, materials, and supplies.

    (a) Test systems must be selected by the laboratory. The testing 
must be performed following the manufacturer's instructions and in a 
manner that provides test results within the laboratory's stated 
performance specifications for each test system as determined under 
Sec.  493.1253.
    (b) The laboratory must define criteria for those conditions that 
are essential for proper storage of reagents and specimens, accurate 
and reliable test system operation, and test result reporting. The 
criteria must be consistent with the manufacturer's instructions, if 
provided. These conditions must be monitored and documented and, if 
applicable, include the following:
    (1) Water quality.
    (2) Temperature.
    (3) Humidity.
    (4) Protection of equipment and instruments from fluctuations and 
interruptions in electrical current that adversely affect patient test 
results and test reports.
    (c) Reagents, solutions, culture media, control materials, 
calibration materials, and other supplies, as appropriate, must be 
labeled to indicate the following:
    (1) Identity and when significant, titer, strength or 
concentration.
    (2) Storage requirements.
    (3) Preparation and expiration dates.
    (4) Other pertinent information required for proper use.
    (d) Reagents, solutions, culture media, control materials, 
calibration materials,

[[Page 3707]]

and other supplies must not be used when they have exceeded their 
expiration date, have deteriorated, or are of substandard quality.
    (e) Components of reagent kits of different lot numbers must not be 
interchanged unless otherwise specified by the manufacturer.


Sec.  493.1253  Standard: Establishment and verification of performance 
specifications.

    (a) Applicability. Laboratories are not required to verify or 
establish performance specifications for any test system used by the 
laboratory before April 24, 2003.
    (b)(1) Verification of performance specifications. Each laboratory 
that introduces an unmodified, FDA-cleared or approved test system must 
do the following before reporting patient test results:
    (i) Demonstrate that it can obtain performance specifications 
comparable to those established by the manufacturer for the following 
performance characteristics:
    (A) Accuracy.
    (B) Precision.
    (C) Reportable range of test results for the test system.
    (ii) Verify that the manufacturer's reference intervals (normal 
values) are appropriate for the laboratory's patient population.
    (2) Establishment of performance specifications. Each laboratory 
that modifies an FDA-cleared or approved test system, or introduces a 
test system not subject to FDA clearance or approval (including methods 
developed in-house and standardized methods such as text book 
procedures, Gram stain, or potassium hydroxide preparations), or uses a 
test system in which performance specifications are not provided by the 
manufacturer must, before reporting patient test results, establish for 
each test system the performance specifications for the following 
performance characteristics, as applicable:
    (i) Accuracy.
    (ii) Precision.
    (iii) Analytical sensitivity.
    (iv) Analytical specificity to include interfering substances.
    (v) Reportable range of test results for the test system.
    (vi) Reference intervals (normal values).
    (vii) Any other performance characteristic required for test 
performance.
    (3) Determination of calibration and control procedures. The 
laboratory must determine the test system's calibration procedures and 
control procedures based upon the performance specifications verified 
or established under paragraph (b)(1) or (b)(2) of this section.
    (c) Documentation. The laboratory must document all activities 
specified in this section.


Sec.  493.1254  Standard: Maintenance and function checks.

    (a) Unmodified manufacturer's equipment, instruments, or test 
systems. The laboratory must perform and document the following:
    (1) Maintenance as defined by the manufacturer and with at least 
the frequency specified by the manufacturer.
    (2) Function checks as defined by the manufacturer and with at 
least the frequency specified by the manufacturer. Function checks must 
be within the manufacturer's established limits before patient testing 
is conducted.
    (b) Equipment, instruments, or test systems developed in-house, 
commercially available and modified by the laboratory, or maintenance 
and function check protocols are not provided by the manufacturer. The 
laboratory must do the following:
    (1)(i) Establish a maintenance protocol that ensures equipment, 
instrument, and test system performance that is necessary for accurate 
and reliable test results and test result reporting.
    (ii) Perform and document the maintenance activities specified in 
paragraph (b)(1)(i) of this section.
    (2)(i) Define a function check protocol that ensures equipment, 
instrument, and test system performance that is necessary for accurate 
and reliable test results and test result reporting.
    (ii) Perform and document the function checks, including background 
or baseline checks, specified in paragraph (b)(2)(i) of this section. 
Function checks must be within the laboratory's established limits 
before patient testing is conducted.


Sec.  493.1255  Standard: Calibration and calibration verification 
procedures.

    Calibration and calibration verification procedures are required to 
substantiate the continued accuracy of the test system throughout the 
laboratory's reportable range of test results for the test system. 
Unless otherwise specified in this subpart, for each applicable test 
system the laboratory must do the following:
    (a) Perform and document calibration procedures--
    (1) Following the manufacturer's test system instructions, using 
calibration materials provided or specified, and with at least the 
frequency recommended by the manufacturer;
    (2) Using the criteria verified or established by the laboratory as 
specified in Sec.  493.1253(b)(3)--
    (i) Using calibration materials appropriate for the test system 
and, if possible, traceable to a reference method or reference material 
of known value; and
    (ii) Including the number, type, and concentration of calibration 
materials, as well as acceptable limits for and the frequency of 
calibration; and
    (3) Whenever calibration verification fails to meet the 
laboratory's acceptable limits for calibration verification.
    (b) Perform and document calibration verification procedures--
    (1) Following the manufacturer's calibration verification 
instructions;
    (2) Using the criteria verified or established by the laboratory 
under Sec.  493.1253(b)(3)--
    (i) Including the number, type, and concentration of the materials, 
as well as acceptable limits for calibration verification; and
    (ii) Including at least a minimal (or zero) value, a mid-point 
value, and a maximum value near the upper limit of the range to verify 
the laboratory's reportable range of test results for the test system; 
and
    (3) At least once every 6 months and whenever any of the following 
occur:
    (i) A complete change of reagents for a procedure is introduced, 
unless the laboratory can demonstrate that changing reagent lot numbers 
does not affect the range used to report patient test results, and 
control values are not adversely affected by reagent lot number 
changes.
    (ii) There is major preventive maintenance or replacement of 
critical parts that may influence test performance.
    (iii) Control materials reflect an unusual trend or shift, or are 
outside of the laboratory's acceptable limits, and other means of 
assessing and correcting unacceptable control values fail to identify 
and correct the problem.
    (iv) The laboratory's established schedule for verifying the 
reportable range for patient test results requires more frequent 
calibration verification.


Sec.  493.1256  Standard: Control procedures.

    (a) For each test system, the laboratory is responsible for having 
control procedures that monitor the accuracy and precision of the 
complete analytical process.
    (b) The laboratory must establish the number, type, and frequency 
of testing control materials using, if applicable, the performance 
specifications verified

[[Page 3708]]

or established by the laboratory as specified in Sec.  493.1253(b)(3).
    (c) The control procedures must--
    (1) Detect immediate errors that occur due to test system failure, 
adverse environmental conditions, and operator performance.
    (2) Monitor over time the accuracy and precision of test 
performance that may be influenced by changes in test system 
performance and environmental conditions, and variance in operator 
performance.
    (d) Unless CMS approves a procedure, specified in Appendix C of the 
State Operations Manual (CMS Pub. 7), that provides equivalent quality 
testing, the laboratory must--
    (1) Perform control procedures as defined in this section unless 
otherwise specified in the additional specialty and subspecialty 
requirements at Sec. Sec.  493.1261 through 493.1278.
    (2) For each test system, perform control procedures using the 
number and frequency specified by the manufacturer or established by 
the laboratory when they meet or exceed the requirements in paragraph 
(d)(3) of this section.
    (3) At least once each day patient specimens are assayed or 
examined perform the following for--
    (i) Each quantitative procedure, include two control materials of 
different concentrations;
    (ii) Each qualitative procedure, include a negative and positive 
control material;
    (iii) Test procedures producing graded or titered results, include 
a negative control material and a control material with graded or 
titered reactivity, respectively;
    (iv) Each test system that has an extraction phase, include two 
control materials, including one that is capable of detecting errors in 
the extraction process; and
    (v) Each molecular amplification procedure, include two control 
materials and, if reaction inhibition is a significant source of false 
negative results, a control material capable of detecting the 
inhibition.
    (4) For thin layer chromatography--
    (i) Spot each plate or card, as applicable, with a calibrator 
containing all known substances or drug groups, as appropriate, which 
are identified by thin layer chromatography and reported by the 
laboratory; and
    (ii) Include at least one control material on each plate or card, 
as applicable, which must be processed through each step of patient 
testing, including extraction processes.
    (5) For each electrophoretic procedure include, concurrent with 
patient specimens, at least one control material containing the 
substances being identified or measured.
    (6) Perform control material testing as specified in this paragraph 
before resuming patient testing when a complete change of reagents is 
introduced; major preventive maintenance is performed; or any critical 
part that may influence test performance is replaced.
    (7) Over time, rotate control material testing among all operators 
who perform the test.
    (8) Test control materials in the same manner as patient specimens.
    (9) When using calibration material as a control material, use 
calibration material from a different lot number than that used to 
establish a cut-off value or to calibrate the test system.
    (10) Establish or verify the criteria for acceptability of all 
control materials.
    (i) When control materials providing quantitative results are used, 
statistical parameters (for example, mean and standard deviation) for 
each batch and lot number of control materials must be defined and 
available.
    (ii) The laboratory may use the stated value of a commercially 
assayed control material provided the stated value is for the 
methodology and instrumentation employed by the laboratory and is 
verified by the laboratory.
    (iii) Statistical parameters for unassayed control materials must 
be established over time by the laboratory through concurrent testing 
of control materials having previously determined statistical 
parameters.
    (e) For reagent, media, and supply checks, the laboratory must do 
the following:
    (1) Check each batch (prepared in-house), lot number (commercially 
prepared) and shipment of reagents, disks, stains, antisera, and 
identification systems (systems using two or more substrates or two or 
more reagents, or a combination) when prepared or opened for positive 
and negative reactivity, as well as graded reactivity, if applicable.
    (2) Each day of use (unless otherwise specified in this subpart), 
test staining materials for intended reactivity to ensure predictable 
staining characteristics. Control materials for both positive and 
negative reactivity must be included, as appropriate.
    (3) Check fluorescent and immunohistochemical stains for positive 
and negative reactivity each time of use.
    (4) Before, or concurrent with the initial use--
    (i) Check each batch of media for sterility if sterility is 
required for testing;
    (ii) Check each batch of media for its ability to support growth 
and, as appropriate, select or inhibit specific organisms or produce a 
biochemical response; and
    (iii) Document the physical characteristics of the media when 
compromised and report any deterioration in the media to the 
manufacturer.
    (5) Follow the manufacturer's specifications for using reagents, 
media, and supplies and be responsible for results.
    (f) Results of control materials must meet the laboratory's and, as 
applicable, the manufacturer's test system criteria for acceptability 
before reporting patient test results.
    (g) The laboratory must document all control procedures performed.
    (h) If control materials are not available, the laboratory must 
have an alternative mechanism to detect immediate errors and monitor 
test system performance over time. The performance of alternative 
control procedures must be documented.


Sec.  493.1261  Standard: Bacteriology.

    (a) The laboratory must check the following for positive and 
negative reactivity using control organisms:
    (1) Each day of use for beta-lactamase methods other than 
Cefinase\TM\.
    (2) Each week of use for Gram stains.
    (3) When each batch (prepared in-house), lot number (commercially 
prepared), and shipment of antisera is prepared or opened, and once 
every 6 months thereafter.
    (b) For antimicrobial susceptibility tests, the laboratory must 
check each batch of media and each lot number and shipment of 
antimicrobial agent(s) before, or concurrent with, initial use, using 
approved control organisms.
    (1) Each day tests are performed, the laboratory must use the 
appropriate control organism(s) to check the procedure.
    (2) The laboratory's zone sizes or minimum inhibitory concentration 
for control organisms must be within established limits before 
reporting patient results.
    (c) The laboratory must document all control procedures performed, 
as specified in this section.


Sec.  493.1262  Standard: Mycobacteriology.

    (a) Each day of use, the laboratory must check all reagents or test 
procedures used for mycobacteria identification with at least one acid-
fast organism that produces a positive reaction and an acid-fast 
organism that produces a negative reaction.
    (b) For antimycobacterial susceptibility tests, the laboratory must

[[Page 3709]]

check each batch of media and each lot number and shipment of 
antimycobacterial agent(s) before, or concurrent with, initial use, 
using an appropriate control organism(s).
    (1) The laboratory must establish limits for acceptable control 
results.
    (2) Each week tests are performed, the laboratory must use the 
appropriate control organism(s) to check the procedure.
    (3) The results for the control organism(s) must be within 
established limits before reporting patient results.
    (c) The laboratory must document all control procedures performed, 
as specified in this section.


Sec.  493.1263  Standard: Mycology.

    (a) The laboratory must check each batch (prepared in-house), lot 
number (commercially prepared), and shipment of lactophenol cotton blue 
when prepared or opened for intended reactivity with a control 
organism(s).
    (b) For antifungal susceptibility tests, the laboratory must check 
each batch of media and each lot number and shipment of antifungal 
agent(s) before, or concurrent with, initial use, using an appropriate 
control organism(s).
    (1) The laboratory must establish limits for acceptable control 
results.
    (2) Each day tests are performed, the laboratory must use the 
appropriate control organism(s) to check the procedure.
    (3) The results for the control organism(s) must be within 
established limits before reporting patient results.
    (c) The laboratory must document all control procedures performed, 
as specified in this section.


Sec.  493.1264  Standard: Parasitology.

    (a) The laboratory must have available a reference collection of 
slides or photographs and, if available, gross specimens for 
identification of parasites and use these references in the laboratory 
for appropriate comparison with diagnostic specimens.
    (b) The laboratory must calibrate and use the calibrated ocular 
micrometer for determining the size of ova and parasites, if size is a 
critical parameter.
    (c) Each month of use, the laboratory must check permanent stains 
using a fecal sample control material that will demonstrate staining 
characteristics.
    (d) The laboratory must document all control procedures performed, 
as specified in this section.


Sec.  493.1265  Standard: Virology.

    (a) When using cell culture to isolate or identify viruses, the 
laboratory must simultaneously incubate a cell substrate control or 
uninoculated cells as a negative control material.
    (b) The laboratory must document all control procedures performed, 
as specified in this section.


Sec.  493.1267  Standard: Routine chemistry.

    For blood gas analyses, the laboratory must perform the following:
    (a) Calibrate or verify calibration according to the manufacturer's 
specifications and with at least the frequency recommended by the 
manufacturer.
    (b) Test one sample of control material each 8 hours of testing 
using a combination of control materials that include both low and high 
values on each day of testing.
    (c) Test one sample of control material each time specimens are 
tested unless automated instrumentation internally verifies calibration 
at least every 30 minutes.
    (d) Document all control procedures performed, as specified in this 
section.


Sec.  493.1269  Standard: Hematology.

    (a) For manual cell counts performed using a hemocytometer--
    (1) One control material must be tested each 8 hours of operation; 
and
    (2) Patient specimens and control materials must be tested in 
duplicate.
    (b) For all nonmanual coagulation test systems, the laboratory must 
include two levels of control material each 8 hours of operation and 
each time a reagent is changed.
    (c) For manual coagulation tests--
    (1) Each individual performing tests must test two levels of 
control materials before testing patient samples and each time a 
reagent is changed; and
    (2) Patient specimens and control materials must be tested in 
duplicate.
    (d) The laboratory must document all control procedures performed, 
as specified in this section.


Sec.  493.1271  Standard: Immunohematology.

    (a) Patient testing. (1) The laboratory must perform ABO grouping, 
D(Rho) typing, unexpected antibody detection, antibody identification, 
and compatibility testing by following the manufacturer's instructions, 
if provided, and as applicable, 21 CFR 606.151(a) through (e).
    (2) The laboratory must determine ABO group by concurrently testing 
unknown red cells with, at a minimum, anti-A and anti-B grouping 
reagents. For confirmation of ABO group, the unknown serum must be 
tested with known A1 and B red cells.
    (3) The laboratory must determine the D(Rho) type by testing 
unknown red cells with anti-D (anti-Rho) blood typing reagent.
    (b) Immunohematological testing and distribution of blood and blood 
products. Blood and blood product testing and distribution must comply 
with 21 CFR 606.100(b)(12); 606.160(b)(3)(ii) and (b)(3)(v); 610.40; 
640.5(a), (b), (c), and (e); and 640.11(b).
    (c) Blood and blood products storage. Blood and blood products must 
be stored under appropriate conditions that include an adequate 
temperature alarm system that is regularly inspected.
    (1) An audible alarm system must monitor proper blood and blood 
product storage temperature over a 24-hour period.
    (2) Inspections of the alarm system must be documented.
    (d) Retention of samples of transfused blood. According to the 
laboratory's established procedures, samples of each unit of transfused 
blood must be retained for further testing in the event of transfusion 
reactions. The laboratory must promptly dispose of blood not retained 
for further testing that has passed its expiration date.
    (e) Investigation of transfusion reactions. (1) According to its 
established procedures, the laboratory that performs compatibility 
testing, or issues blood or blood products, must promptly investigate 
all transfusion reactions occurring in facilities for which it has 
investigational responsibility and make recommendations to the medical 
staff regarding improvements in transfusion procedures.
    (2) The laboratory must document, as applicable, that all necessary 
remedial actions are taken to prevent recurrences of transfusion 
reactions and that all policies and procedures are reviewed to assure 
they are adequate to ensure the safety of individuals being transfused.
    (f) The laboratory must document all control procedures performed, 
as specified in this section.


Sec.  493.1273  Standard: Histopathology.

    (a) Fluorescent and immunohistochemical stains must be checked for 
positive and negative reactivity each time of use. For all other 
differential or special stains, a control slide of known reactivity 
must be stained with each patient slide or group of patient slides. 
Reaction(s) of the control slide with each special stain must be 
documented.
    (b) The laboratory must retain stained slides, specimen blocks, and 
tissue remnants as specified in Sec.  493.1105. The remnants of tissue 
specimens must be maintained in a manner that ensures proper 
preservation of the tissue specimens until the portions submitted for 
microscopic examination have been examined and a diagnosis made by an

[[Page 3710]]

individual qualified under Sec. Sec.  493.1449(b), (l), or (m).
    (c) An individual who has successfully completed a training program 
in neuromuscular pathology approved by HHS may examine and provide 
reports for neuromuscular pathology.
    (d) Tissue pathology reports must be signed by an individual 
qualified as specified in paragraph (b) or, as appropriate, paragraph 
(c) of this section. If a computer report is generated with an 
electronic signature, it must be authorized by the individual who 
performed the examination and made the diagnosis.
    (e) The laboratory must use acceptable terminology of a recognized 
system of disease nomenclature in reporting results.
    (f) The laboratory must document all control procedures performed, 
as specified in this section.


Sec.  493.1274  Standard: Cytology.

    (a) Cytology slide examination site. All cytology slide 
preparations must be evaluated on the premises of a laboratory 
certified to conduct testing in the subspecialty of cytology.
    (b) Staining. The laboratory must have available and follow written 
policies and procedures for each of the following, if applicable:
    (1) All gynecologic slide preparations must be stained using a 
Papanicolaou or modified Papanicolaou staining method.
    (2) Effective measures to prevent cross-contamination between 
gynecologic and nongynecologic specimens during the staining process 
must be used.
    (3) Nongynecologic specimens that have a high potential for cross-
contamination must be stained separately from other nongynecologic 
specimens, and the stains must be filtered or changed following 
staining.
    (c) Control procedures. The laboratory must establish and follow 
written policies and procedures for a program designed to detect errors 
in the performance of cytologic examinations and the reporting of 
results. The program must include the following:
    (1) A review of slides from at least 10 percent of the gynecologic 
cases interpreted by individuals qualified under Sec. Sec.  493.1469 or 
493.1483, to be negative for epithelial cell abnormalities and other 
malignant neoplasms (as defined in paragraph (e)(1) of this section).
    (i) The review must be performed by an individual who meets one of 
the following qualifications:
    (A) A technical supervisor qualified under Sec. Sec.  493.1449(b) 
or (k).
    (B) A cytology general supervisor qualified under Sec.  493.1469.
    (C) A cytotechnologist qualified under Sec.  493.1483 who has the 
experience specified in Sec.  493.1469(b)(2).
    (ii) Cases must be randomly selected from the total caseload and 
include negatives and those from patients or groups of patients that 
are identified as having a higher than average probability of 
developing cervical cancer based on available patient information.
    (iii) The review of those cases selected must be completed before 
reporting patient results.
    (2) Laboratory comparison of clinical information, when available, 
with cytology reports and comparison of all gynecologic cytology 
reports with a diagnosis of high-grade squamous intraepithelial lesion 
(HSIL), adenocarcinoma, or other malignant neoplasms with the 
histopathology report, if available in the laboratory (either on-site 
or in storage), and determination of the causes of any discrepancies.
    (3) For each patient with a current HSIL, adenocarcinoma, or other 
malignant neoplasm, laboratory review of all normal or negative 
gynecologic specimens received within the previous 5 years, if 
available in the laboratory (either on-site or in storage). If 
significant discrepancies are found that will affect current patient 
care, the laboratory must notify the patient's physician and issue an 
amended report.
    (4) Records of initial examinations and all rescreening results 
must be documented.
    (5) An annual statistical laboratory evaluation of the number of--
    (i) Cytology cases examined;
    (ii) Specimens processed by specimen type;
    (iii) Patient cases reported by diagnosis (including the number 
reported as unsatisfactory for diagnostic interpretation);
    (iv) Gynecologic cases with a diagnosis of HSIL, adenocarcinoma, or 
other malignant neoplasm for which histology results were available for 
comparison;
    (v) Gynecologic cases where cytology and histology are discrepant; 
and
    (vi) Gynecologic cases where any rescreen of a normal or negative 
specimen results in reclassification as low-grade squamous 
intraepithelial lesion (LSIL), HSIL, adenocarcinoma, or other malignant 
neoplasms.
    (6) An evaluation of the case reviews of each individual examining 
slides against the laboratory's overall statistical values, 
documentation of any discrepancies, including reasons for the deviation 
and, if appropriate, corrective actions taken.
    (d) Workload limits. The laboratory must establish and follow 
written policies and procedures that ensure the following:
    (1) The technical supervisor establishes a maximum workload limit 
for each individual who performs primary screening.
    (i) The workload limit is based on the individual's performance 
using evaluations of the following:
    (A) Review of 10 percent of the cases interpreted as negative for 
the conditions defined in paragraph (e)(1) of this section.
    (B) Comparison of the individual's interpretation with the 
technical supervisor's confirmation of patient smears specified in 
paragraphs (e)(1) and (e)(3) of this section.
    (ii) Each individual's workload limit is reassessed at least every 
6 months and adjusted when necessary.
    (2) The maximum number of slides examined by an individual in each 
24-hour period does not exceed 100 slides (one patient specimen per 
slide; gynecologic, nongynecologic, or both) irrespective of the site 
or laboratory. This limit represents an absolute maximum number of 
slides and must not be employed as an individual's performance target. 
In addition--
    (i) The maximum number of 100 slides is examined in no less than an 
8-hour workday;
    (ii) For the purposes of establishing workload limits for 
individuals examining slides in less than an 8-hour workday (includes 
full-time employees with duties other than slide examination and part-
time employees), a period of 8 hours is used to prorate the number of 
slides that may be examined. The formula--
[GRAPHIC] [TIFF OMITTED] TR24JA03.000


is used to determine maximum slide volume to be examined;
    (iii) Nongynecologic slide preparation made using liquid-based 
slide preparatory techniques that result in cell dispersion over one-
half or less of the total available slide may be counted as one-half 
slide; and
    (iv) Technical supervisors who perform primary screening are not 
required to include tissue pathology slides and previously examined 
cytology slides (gynecologic and nongynecologic) in the 100 slide 
workload limit.
    (3) The laboratory must maintain records of the total number of 
slides examined by each individual during

[[Page 3711]]

each 24-hour period and the number of hours spent examining slides in 
the 24-hour period irrespective of the site or laboratory.
    (4) Records are available to document the workload limit for each 
individual.
    (e) Slide examination and reporting. The laboratory must establish 
and follow written policies and procedures that ensure the following:
    (1) A technical supervisor confirms each gynecologic slide 
preparation interpreted to exhibit reactive or reparative changes or 
any of the following epithelial cell abnormalities:
    (i) Squamous cell.
    (A) Atypical squamous cells of undetermined significance (ASC-US) 
or cannot exclude HSIL (ASC-H).
    (B) LSIL-Human papillomavirus (HPV)/mild dysplasia/cervical 
intraepithelial neoplasia 1 (CIN 1).
    (C) HSIL-moderate and severe dysplasia, carcinoma in situ (CIS)/CIN 
2 and CIN 3 or with features suspicious for invasion.
    (D) Squamous cell carcinoma.
    (ii) Glandular cell.
    (A) Atypical cells not otherwise specified (NOS) or specified in 
comments (endocervical, endometrial, or glandular).
    (B) Atypical cells favor neoplastic (endocervical or glandular).
    (C) Endocervical adenocarcinoma in situ.
    (D) Adenocarcinoma endocervical, adenocarcinoma endometrial, 
adenocarcinoma extrauterine, and adenocarcinoma NOS.
    (iii) Other malignant neoplasms.
    (2) The report of gynecologic slide preparations with conditions 
specified in paragraph (e)(1) of this section must be signed to reflect 
the technical supervisory review or, if a computer report is generated 
with signature, it must reflect an electronic signature authorized by 
the technical supervisor who performed the review.
    (3) All nongynecologic preparations are reviewed by a technical 
supervisor. The report must be signed to reflect technical supervisory 
review or, if a computer report is generated with signature, it must 
reflect an electronic signature authorized by the technical supervisor 
who performed the review.
    (4) Unsatisfactory specimens or slide preparations are identified 
and reported as unsatisfactory.
    (5) The report contains narrative descriptive nomenclature for all 
results.
    (6) Corrected reports issued by the laboratory indicate the basis 
for correction.
    (f) Record and slide retention. (1) The laboratory must retain all 
records and slide preparations as specified in Sec.  493.1105.
    (2) Slides may be loaned to proficiency testing programs in lieu of 
maintaining them for the required time period, provided the laboratory 
receives written acknowledgment of the receipt of slides by the 
proficiency testing program and maintains the acknowledgment to 
document the loan of these slides.
    (3) Documentation of slides loaned or referred for purposes other 
than proficiency testing must be maintained.
    (4) All slides must be retrievable upon request.
    (g) Automated and semi-automated screening devices. When performing 
evaluations using automated and semi-automated screening devices, the 
laboratory must follow manufacturer's instructions for preanalytic, 
analytic, and postanalytic phases of testing, as applicable, and meet 
the applicable requirements of this subpart K.
    (h) The laboratory must document all control procedures performed, 
as specified in this section.


Sec.  493.1276  Standard: Clinical cytogenetics.

    (a) The laboratory must have policies and procedures for ensuring 
accurate and reliable patient specimen identification during the 
process of accessioning, cell preparation, photographing or other image 
reproduction technique, photographic printing, and reporting and 
storage of results, karyotypes, and photographs.
    (b) The laboratory must have records that document the following:
    (1) The media used, reactions observed, number of cells counted, 
number of cells karyotyped, number of chromosomes counted for each 
metaphase spread, and the quality of the banding.
    (2) The resolution is appropriate for the type of tissue or 
specimen and the type of study required based on the clinical 
information provided to the laboratory.
    (3) An adequate number of karyotypes are prepared for each patient.
    (c) Determination of sex must be performed by full chromosome 
analysis.
    (d) The laboratory report must include a summary and interpretation 
of the observations, number of cells counted and analyzed, and use the 
International System of Cytogenetic Nomenclature.
    (e) The laboratory must document all control procedures performed, 
as specified in this section.


Sec.  493.1278  Standard: Histocompatibility.

    (a) General. The laboratory must meet the following requirements:
    (1) An audible alarm system must be used to monitor the storage 
temperature of specimens (donor and recipient) and reagents. The 
laboratory must have an emergency plan for alternate storage.
    (2) All patient specimens must be easily retrievable.
    (3) Reagent typing sera inventory prepared in-house must indicate 
source, bleeding date and identification number, reagent specificity, 
and volume remaining.
    (4) If the laboratory uses immunologic reagents (for example, 
antibodies, antibody-coated particles, or complement) to facilitate or 
enhance the isolation of lymphocytes, or lymphocyte subsets, the 
efficacy of the methods must be monitored with appropriate quality 
control procedures.
    (5) Participate in at least one national or regional cell exchange 
program, if available, or develop an exchange system with another 
laboratory in order to validate interlaboratory reproducibility.
    (b) HLA typing. The laboratory must do the following:
    (1) Use a technique(s) that is established to optimally define, as 
applicable, HLA Class I and II specificities.
    (2) HLA type all potential transplant recipients at a level 
appropriate to support clinical transplant protocol and donor 
selection.
    (3) HLA type cells from organ donors referred to the laboratory.
    (4) Use HLA antigen terminology that conforms to the latest report 
of the World Health Organization (W.H.O.) Committee on Nomenclature. 
Potential new antigens not yet approved by this committee must have a 
designation that cannot be confused with W.H.O. terminology.
    (5) Have available and follow written criteria for the following:
    (i) The preparation of cells or cellular extracts (for example, 
solubilized antigens and nucleic acids), as applicable to the HLA 
typing technique(s) performed.
    (ii) Selecting typing reagents, whether prepared in-house or 
commercially.
    (iii) Ensuring that reagents used for typing are adequate to define 
all HLA-A, B and DR specificities that are officially recognized by the 
most recent W.H.O. Committee on Nomenclature and for which reagents are 
readily available.
    (iv) The assignment of HLA antigens.
    (v) When antigen redefinition and retyping are required.
    (6) Check each HLA typing by testing, at a minimum the following:
    (i) A positive control material.
    (ii) A negative control material in which, if applicable to the 
technique performed, cell viability at the end of

[[Page 3712]]

incubation is sufficient to permit accurate interpretation of results. 
In assays in which cell viability is not required, the negative control 
result must be sufficiently different from the positive control result 
to permit accurate interpretation of results.
    (iii) Positive control materials for specific cell types when 
applicable (that is, T cells, B cells, and monocytes).
    (c) Disease-associated studies. The laboratory must check each 
typing for disease-associated HLA antigens using control materials to 
monitor the test components and each phase of the test system to ensure 
acceptable performance.
    (d) Antibody Screening. The laboratory must do the following:
    (1) Use a technique(s) that detects HLA-specific antibody with a 
specificity equivalent or superior to that of the basic complement-
dependent microlymphocytotoxicity assay.
    (2) Use a method that distinguishes antibodies to HLA Class II 
antigens from antibodies to Class I antigens to detect antibodies to 
HLA Class II antigens.
    (3) Use a panel that contains all the major HLA specificities and 
common splits. If the laboratory does not use commercial panels, it 
must maintain a list of individuals for fresh panel bleeding.
    (4) Make a reasonable attempt to have available monthly serum 
specimens for all potential transplant recipients for periodic antibody 
screening and crossmatch.
    (5) Have available and follow a written policy consistent with 
clinical transplant protocols for the frequency of screening potential 
transplant recipient sera for preformed HLA-specific antibodies.
    (6) Check each antibody screening by testing, at a minimum the 
following:
    (i) A positive control material containing antibodies of the 
appropriate isotype for the assay.
    (ii) A negative control material.
    (7) As applicable, have available and follow written criteria and 
procedures for antibody identification to the level appropriate to 
support clinical transplant protocol.
    (e) Crossmatching. The laboratory must do the following:
    (1) Use a technique(s) documented to have increased sensitivity in 
comparison with the basic complement-dependent microlymphocytotoxicity 
assay.
    (2) Have available and follow written criteria for the following:
    (i) Selecting appropriate patient serum samples for crossmatching.
    (ii) The preparation of donor cells or cellular extracts (for 
example, solubilized antigens and nucleic acids), as applicable to the 
crossmatch technique(s) performed.
    (3) Check each crossmatch and compatibility test for HLA Class II 
antigenic differences using control materials to monitor the test 
components and each phase of the test system to ensure acceptable 
performance.
    (f) Transplantation. Laboratories performing histocompatibility 
testing for transfusion and transplantation purposes must do the 
following:
    (1) Have available and follow written policies and protocols 
specifying the histocompatibility testing (that is, HLA typing, 
antibody screening, compatibility testing and crossmatching) to be 
performed for each type of cell, tissue or organ to be transfused or 
transplanted. The laboratory's policies must include, as applicable--
    (i) Testing protocols for cadaver donor, living, living-related, 
and combined organ and tissue transplants;
    (ii) Testing protocols for patients at high risk for allograft 
rejection; and
    (iIi) The level of testing required to support clinical transplant 
protocols (for example, antigen or allele level).
    (2) For renal allotransplantation and combined organ and tissue 
transplants in which a kidney is to be transplanted, have available 
results of final crossmatches before the kidney is transplanted.
    (3) For nonrenal transplantation, if HLA testing and final 
crossmatches were not performed prospectively because of an emergency 
situation, the laboratory must document the circumstances, if known, 
under which the emergency transplant was performed, and records of the 
transplant must reflect any information provided to the laboratory by 
the patient's physician.
    (g) The laboratory must document all control procedures performed, 
as specified in this section.


Sec.  493.1281  Standard: Comparison of test results.

    (a) If a laboratory performs the same test using different 
methodologies or instruments, or performs the same test at multiple 
testing sites, the laboratory must have a system that twice a year 
evaluates and defines the relationship between test results using the 
different methodologies, instruments, or testing sites.
    (b) The laboratory must have a system to identify and assess 
patient test results that appear inconsistent with the following 
relevant criteria, when available:
    (1) Patient age.
    (2) Sex.
    (3) Diagnosis or pertinent clinical data.
    (4) Distribution of patient test results.
    (5) Relationship with other test parameters.
    (c) The laboratory must document all test result comparison 
activities.


Sec.  493.1282  Standard: Corrective actions.

    (a) Corrective action policies and procedures must be available and 
followed as necessary to maintain the laboratory's operation for 
testing patient specimens in a manner that ensures accurate and 
reliable patient test results and reports.
    (b) The laboratory must document all corrective actions taken, 
including actions taken when any of the following occur:
    (1) Test systems do not meet the laboratory's verified or 
established performance specifications, as determined in Sec.  
493.1253(b), which include but are not limited to--
    (i) Equipment or methodologies that perform outside of established 
operating parameters or performance specifications;
    (ii) Patient test values that are outside of the laboratory's 
reportable range of test results for the test system; and
    (iii) When the laboratory determines that the reference intervals 
(normal values) for a test procedure are inappropriate for the 
laboratory's patient population.
    (2) Results of control or calibration materials, or both, fail to 
meet the laboratory's established criteria for acceptability. All 
patient test results obtained in the unacceptable test run and since 
the last acceptable test run must be evaluated to determine if patient 
test results have been adversely affected. The laboratory must take the 
corrective action necessary to ensure the reporting of accurate and 
reliable patient test results.
    (3) The criteria for proper storage of reagents and specimens, as 
specified under Sec.  493.1252(b), are not met.


Sec.  493.1283  Standard: Test records.

    (a) The laboratory must maintain an information or record system 
that includes the following:
    (1) The positive identification of the specimen.
    (2) The date and time of specimen receipt into the laboratory.
    (3) The condition and disposition of specimens that do not meet the 
laboratory's criteria for specimen acceptability.
    (4) The records and dates of all specimen testing, including the 
identity

[[Page 3713]]

of the personnel who performed the test(s).
    (b) Records of patient testing including, if applicable, instrument 
printouts, must be retained.


Sec.  493.1289  Standard: Analytic systems assessment.

    (a) The laboratory must establish and follow written policies and 
procedures for an ongoing mechanism to monitor, assess, and when 
indicated, correct problems identified in the analytic systems 
specified in Sec. Sec.  493.1251 through 493.1283.
    (b) The analytic systems assessment must include a review of the 
effectiveness of corrective actions taken to resolve problems, revision 
of policies and procedures necessary to prevent recurrence of problems, 
and discussion of analytic systems assessment reviews with appropriate 
staff.
    (c) The laboratory must document all analytic systems assessment 
activities.

Postanalytic Systems


Sec.  493.1290  Condition: Postanalytic systems.

    Each laboratory that performs nonwaived testing must meet the 
applicable postanalytic systems requirements in Sec.  493.1291 unless 
HHS approves a procedure, specified in Appendix C of the State 
Operations Manual (CMS Pub. 7) that provides equivalent quality 
testing. The laboratory must monitor and evaluate the overall quality 
of the postanalytic systems and correct identified problems as 
specified in Sec.  493.1299 for each specialty and subspecialty of 
testing performed.


Sec.  493.1291  Standard: Test report.

    (a) The laboratory must have adequate manual or electronic systems 
in place to ensure test results and other patient-specific data are 
accurately and reliably sent from the point of data entry (whether 
interfaced or entered manually) to final report destination, in a 
timely manner. This includes the following:
    (1) Results reported from calculated data.
    (2) Results and patient-specific data electronically reported to 
network or interfaced systems.
    (3) Manually transcribed or electronically transmitted results and 
patient-specific information reported directly or upon receipt from 
outside referral laboratories, satellite or point-of-care testing 
locations.
    (b) Test report information maintained as part of the patient's 
chart or medical record must be readily available to the laboratory and 
to CMS or a CMS agent upon request.
    (c) The test report must indicate the following:
    (1) For positive patient identification, either the patient's name 
and identification number, or an unique patient identifier and 
identification number.
    (2) The name and address of the laboratory location where the test 
was performed.
    (3) The test report date.
    (4) The test performed.
    (5) Specimen source, when appropriate.
    (6) The test result and, if applicable, the units of measurement or 
interpretation, or both.
    (7) Any information regarding the condition and disposition of 
specimens that do not meet the laboratory's criteria for acceptability.
    (d) Pertinent ``reference intervals'' or ``normal'' values, as 
determined by the laboratory performing the tests, must be available to 
the authorized person who ordered the tests and, if applicable, the 
individual responsible for using the test results.
    (e) The laboratory must, upon request, make available to clients a 
list of test methods employed by the laboratory and, as applicable, the 
performance specifications established or verified as specified in 
Sec.  493.1253. In addition, information that may affect the 
interpretation of test results, for example test interferences, must be 
provided upon request. Pertinent updates on testing information must be 
provided to clients whenever changes occur that affect the test results 
or interpretation of test results.
    (f) Test results must be released only to authorized persons and, 
if applicable, the individual responsible for using the test results 
and the laboratory that initially requested the test.
    (g) The laboratory must immediately alert the individual or entity 
requesting the test and, if applicable, the individual responsible for 
using the test results when any test result indicates an imminent life-
threatening condition, or panic or alert values.
    (h) When the laboratory cannot report patient test results within 
its established time frames, the laboratory must determine, based on 
the urgency of the patient test(s) requested, the need to notify the 
appropriate individual(s) of the delayed testing.
    (i) If a laboratory refers patient specimens for testing--
    (1) The referring laboratory must not revise results or information 
directly related to the interpretation of results provided by the 
testing laboratory;
    (2) The referring laboratory may permit each testing laboratory to 
send the test result directly to the authorized person who initially 
requested the test. The referring laboratory must retain or be able to 
produce an exact duplicate of each testing laboratory's report; and
    (3) The authorized person who orders a test must be notified by the 
referring laboratory of the name and address of each laboratory 
location where the test was performed.
    (j) All test reports or records of the information on the test 
reports must be maintained by the laboratory in a manner that permits 
ready identification and timely accessibility.
    (k) When errors in the reported patient test results are detected, 
the laboratory must do the following:
    (1) Promptly notify the authorized person ordering the test and, if 
applicable, the individual using the test results of reporting errors.
    (2) Issue corrected reports promptly to the authorized person 
ordering the test and, if applicable, the individual using the test 
results.
    (3) Maintain duplicates of the original report, as well as the 
corrected report.


Sec.  493.1299  Standard: Postanalytic systems assessment.

    (a) The laboratory must establish and follow written policies and 
procedures for an ongoing mechanism to monitor, assess and, when 
indicated, correct problems identified in the postanalytic systems 
specified in Sec.  493.1291.
    (b) The postanalytic systems assessment must include a review of 
the effectiveness of corrective actions taken to resolve problems, 
revision of policies and procedures necessary to prevent recurrence of 
problems, and discussion of postanalytic systems assessment reviews 
with appropriate staff.
    (c) The laboratory must document all postanalytic systems 
assessment activities.

Subpart M--Personnel for Nonwaived Testing

    19. Revise the heading of Subpart M to read as set forth above.


Sec.  493.1359  [Amended]

    20. Sec.  493.1359(b)(2), remove the reference to ``subpart P''.


Sec.  493.1407  [Amended]

    21. In Sec.  493.1407(e)(5), remove the word ``assurance'' and, add 
in its place, the word ``assessment''.

    22. In Sec.  493.1443, paragraph (b) introductory text is 
republished, and paragraph (b)(3) is revised to read as follows:

[[Page 3714]]

Sec.  493.1443  Standard: Laboratory director qualifications.

* * * * *
    (b) The laboratory director must--
* * * * *
    (3) Hold an earned doctoral degree in a chemical, physical, 
biological, or clinical laboratory science from an accredited 
institution and--
    (i) Be certified and continue to be certified by a board approved 
by HHS; or
    (ii) Before February 24, 2003, must have served or be serving as a 
director of a laboratory performing high complexity testing and must 
have at least--
    (A) Two years of laboratory training or experience, or both; and
    (B) Two years of laboratory experience directing or supervising 
high complexity testing.
* * * * *


Sec.  493.1445  [Amended]

    23. In Sec.  493.1445(e)(5), remove the word ``assurance'' and add, 
in its place, the word ``assessment''.


Sec.  493.1451  [Amended]

    24. In Sec.  493.1451(c)(4), remove the cross reference to ``Sec.  
493.1257(c)'' and add, in its place, ``Sec.  493.1274(d) and (e)''.


Sec.  493.1471 and Sec.  493.1485  [Amended]

    25. In Sec. Sec.  493.1471(b)(2) and 493.1485(a), remove the cross 
reference to ``Sec.  493.1257(d)'' and add, in its place, ``Sec.  
493.1274(c)''.

Subpart P--[Reserved]

    26. Subpart P consisting of Sec. Sec.  493.1701 through 493.1721, 
is removed and reserved.

Subpart R--Enforcement Procedures


Sec.  493.1844  [Amended]

    27. In Sec.  493.1844(c)(1), remove the reference to ``subpart P''.

Subpart T--Consultations


Sec.  493.2001  [Amended]

    28. Amend Sec.  493.2001 as follows:
    a. In paragraph (e)(1), remove the words ``tests and examinations 
of moderate complexity (including the subcategory) and high 
complexity'' and add, in their place, the words ``nonwaived testing''.
    b. Revise paragraph (e)(4) to read as follows:
* * * * *
    (e) * * *
    (4) Facility administration and quality systems standards.
* * * * *

    Dated: October 7, 2002.
Thomas A. Scully,
Administrator, Centers for Medicare & Medicaid Services.

    Dated: December 13, 2002.
Tommy G. Thompson,
Secretary.
[FR Doc. 03-1230 Filed 1-23-03; 8:45 am]
BILLING CODE 4120-01-P