[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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This Federal Register document is also available from the Federal
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Government Printing Office. This Web site address is: http://www.access.gpo/nara/index.html.
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
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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
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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)
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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)
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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.
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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.
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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