[Federal Register: January 24, 2003 (Volume 68, Number 16)]
[Rules and Regulations]
[Page 3639-3714]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr24ja03-23]
[[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 Quality Systems and Certain Personnel Qualifications; Final Rule
[[Page 3640]]
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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.
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.
I. Background
On February 28, 1992, we published a final rule with comment period
in the Federal Register (57 FR 7002) that set forth the requirements
for laboratories that are subject to the Clinical Laboratory
Improvement Amendments of 1988 (CLIA).
Under the provisions of the sentence following section 1861(s)(15)
through 1861(s)(17) of the Social Security Act, (the Act) any
laboratory that wants to be paid for services furnished to Medicare
beneficiaries must meet the requirements of section 353 of the Public
Health Services Act. Subject to specified exceptions, all laboratories,
regardless of whether they receive payment from the Medicare or
Medicaid programs must have a current and valid CLIA certificate to
test human specimens. The February 28, 1992 final rule with comment
period established uniform requirements based on the complexity of
testing performed by laboratories regardless of the laboratory's
location, size, or type. In the interest of public health, we included
requirements in the February 28, 1992 final rule with comment period to
ensure the quality of laboratory services.
We recognized that it would take time and resources for
laboratories to understand and to implement the new requirements
contained in the February 28, 1992 final rule with comment period. This
final rule completes the phase-in of certain requirements where the
comments supported taking this action.
The phased-in provision included quality control (QC) requirements
applicable to moderate complexity tests and the date by which an
individual with a doctorial degree must possess board certification to
qualify as a director of a laboratory that performs high complexity
testing.
During the phase-in, the Food and Drug Administration (FDA) was to
establish a process to review and clear manufacturers' QC instructions
for CLIA QC purposes. Because the CLIA program is user fee funded, we
decided it would be prudent to wait until the phase-in period ended
before implementing the FDA QC review. This afforded us the survey
experience necessary to determine whether an additional FDA review
process beyond that already in place as part of the premarket review
would be of benefit to laboratories. We realized through our experience
inspecting laboratories that an additional FDA review would not be of
such benefit. We decided to remove this prospective provision.
Therefore, we are removing all references to the FDA CLIA QC clearance
process that was not implemented.
The phase-in effective dates contained in the February 28, 1992
final rule with comment period were further extended in the final rules
with comment period published on December 6, 1994 in the Federal
Register (59 FR 62606), May 12, 1997 in the Federal Register (62 FR
25855), October 14, 1998 in the Federal Register (63 FR 55031), and
December 29, 2000 in the Federal Register (65 FR 82941).
The extensions allowed previously unregulated laboratories time to
understand and implement these requirements. The extensions also
provided the Department of Health and Human Services (HHS) additional
time to issue revised QC requirements, review board certification
program requests for approval, and ensure that laboratory directors
with a doctoral degree had sufficient time to successfully complete the
requirements for board certification.
On December 28, 2001, we published a proposed rule in the Federal
Register (66 FR 67163) seeking comments on provisions to revise and
expand the qualification requirements by which an individual with a
doctoral degree in a chemical, physical, biological, or clinical
laboratory science from an accredited institution may qualify to serve
as a director of a laboratory performing high complexity testing. The
[[Page 3641]]
three proposed alternative qualification pathways were as follows:
[sbull] On or after January 1, 2003, be certified and continue to
be certified by a board approved by HHS.
[sbull] Before January 1, 2003, must have served or be serving as a
director of a laboratory performing high complexity testing and must
have at least 2 years of laboratory training or experience, or both;
and 2 years experience directing or supervising high complexity
testing.
[sbull] Have at least 6 years of laboratory training or experience,
or both, including 2 years of experience directing or supervising high
complexity testing.
In this final rule, effective April 24, 2003, all laboratories must
meet and follow the QC requirements. In addition, we are setting forth
qualification requirements for an individual with a doctoral degree to
serve as a director of a laboratory performing high complexity testing.
Effective February 24, 2003, an individual with a doctoral degree may
qualify to serve as a director of a laboratory that performs high
complexity testing if he or she is certified and continues to be
certified by a board approved by HHS; or before the effective date of
this rule, has served or is serving as a director of a laboratory
performing high complexity testing and has acquired at least 2 years of
laboratory training or experience, or both, and 2 years of experience
directing or supervising high complexity testing.
The qualification requirements for high complexity laboratory
directors that are contained in this final rule will become effective
February 24, 2003. To ensure a smooth transition to these new
provisions, we will not be holding facilities out of compliance with
the Board certified regulations of the former rule until the effective
date of this new rule, to the extent the facilities are otherwise in
compliance with the regulations for laboratory directors.
In addition, we are addressing the comments received in response to
the February 28, 1992 final rule with comment period concerning part
493 of title 42 of the Code of Federal Regulations (CFR), subparts I,
J, K, M, and P; comments received in response to the date-extension
rules for certain provisions of subparts K and M; and comments to the
December 28, 2001 proposed rule regarding qualification requirements
for directors of laboratories performing high complexity testing.
II. Highlights and Organization of Final Rule
This regulation contains revisions to part 493 of title 42 of the
CFR. We have renamed, reorganized, and consolidated similar
requirements into one section, deleted duplicate requirements, and
reworded numerous requirements to maintain and/or clarify their
original intent, making the revised regulation easier to read and
understand. In addition to specific changes to subparts I, J, K, M, and
P, applicable technical and conforming changes were also made to other
subparts.
The organization of this regulation now reflects the flow of a
patient specimen through the laboratory, that is, from receipt of the
specimen with the test request through test performance and test result
reporting. In addition, this final rule more accurately describes the
testing requirements and laboratory assessment activities.
In this final rule, the former Subpart I--Proficiency Testing
Programs for Tests of Moderate Complexity (Including the Subcategory),
High Complexity, or Any Combination of These Tests has been renamed
Proficiency Testing Programs for Nonwaived Testing. In addition, in
each specialty and subspecialty area of the subpart, we are restoring
the requirement for the 80 percent agreement used by proficiency
testing programs prior to the February 28, 1992 final rule with comment
period.
The requirements formerly in Subpart J--Patient Test Management for
Moderate Complexity (Including the Subcategory), High Complexity, or
Any Combination of These Tests; Subpart K--Quality Control for Tests of
Moderate Complexity (Including the Subcategory), High Complexity, or
Any Combination of These Tests; and Subpart P--Quality Assurance for
Moderate Complexity (Including the Subcategory) or High Complexity
Testing, or Any Combination of These Tests, are consolidated and
reorganized into a new Subpart J--Facility Administration for Nonwaived
Testing, and Subpart K--Quality Systems for Nonwaived Testing.
As revised by this issuance, subpart J consolidates and clarifies
the facility administration requirements for laboratories performing
nonwaived testing. These include requirements for facility space,
utilities and safety, transfusion services, and record and specimen
retention. Also, subpart J now specifies that laboratories must comply
with Federal, State, and local laboratory requirements. This will allow
CMS to support a Federal, State, or local government that seeks to
protect the public from actions it finds would be detrimental to public
health. In addition, the requirements formerly at Sec. 493.1111 (now
at Sec. 493.1242(c)) have been revised to allow CLIA-certified
laboratories to refer specimens to laboratories operated under the
Veterans Administration (VA), the Department of Defense (DOD), and
CLIA-exempt laboratories within a State whose licensure program has
been granted approval under subpart E.
Requirements pertaining to the total testing process (preanalytic,
analytic, and postanalytic) are now in subpart K. Specifically, subpart
K has been revised to eliminate the QC requirements formerly at Sec.
493.1202 and provisions pertaining to the FDA review and approval of
manufacturers' test system QC for CLIA purposes as specified at Sec.
493.1203 in the February 28, 1992 final rule with comment period. Also,
subpart K is now structured to correlate with the movement of a
specimen through the laboratory from acquisition to examination or
testing, and reporting of results. The requirements were not
substantively changed to correspond to the testing process, but we did
eliminate redundant requirements and revise others for clarification.
In addition, subpart K now incorporates the requirements formerly
in Subpart P--Quality Assurance; Moderate Complexity (Including the
Subcategory) or High Complexity Testing, or Any Combination of These
Tests. These requirements are now located under the appropriate
sections in subpart K, that is, General Laboratory Systems, Preanalytic
Systems, Analytic Systems, and Postanalytic Systems. We listed the
quality assurance (renamed quality assessment (QA) to more clearly
reflect the activities performed) activities for each phase of testing.
For example, QA requirements for preanalytic activities, such as
monitoring the medical necessity and completeness of test request
information solicited and obtained by the laboratory, now appear at the
end of the preanalytic section of subpart K under Sec. 493.1249. We
believe that integrating the QA requirements into the various phases of
the testing process enhances the understanding of the vital and
important role QA plays in ensuring that quality services are provided
by the laboratory throughout the entire testing process. To further
emphasize and clarify the essential components of a comprehensive QA
program, we are reiterating in each assessment section the laboratory's
responsibility to: (1) Establish and follow written polices and
procedures for an ongoing mechanism to monitor and assess each of its
activities; (2) take corrective actions, as necessary, based on these
assessments; (3) review the effectiveness of the assessments and
corrective actions
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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
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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
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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
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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