[Federal Register Volume 60, Number 177 (Wednesday, September 13, 1995)]
[Proposed Rules]
[Pages 47534-47543]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-22378]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Health Care Financing Administration
42 CFR Part 493
[HSQ-225-P]
RIN 0938-AG99
Public Health Service; CLIA Program; Categorization of Waived
Tests
AGENCY: Health Care Financing Administration (HCFA) and Public Health
Service (PHS), HHS.
ACTION: Proposed rule.
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SUMMARY: In this rule we are proposing criteria we would use to
determine whether to categorize specific laboratory tests as waived
from certain requirements of the Clinical Laboratories Improvement
Amendments of 1988. We also propose revisions to requirements that
laboratories performing waived tests must meet.
DATES: Comments will be considered if we receive them at the
appropriate address, as provided below, no later than 5 p.m. on
November 13, 1995.
ADDRESSES: Mail written comments (1 original and 3 copies) to the
following address:
Centers for Disease Control and Prevention, Public Health Service,
Department of Health and Human Services, Attention: HSQ-225-P, 4770
Buford Hwy., NE., MS F11, Atlanta, Georgia 30341-3724.
If you prefer, you may deliver your written comments (1 original
and 3 copies) to the following address:
CDC/Washington, Room 714-B, Hubert H. Humphrey Building, 200
Independence Avenue, SW., Washington, DC 20201.
Because of staffing and resource limitations, we cannot accept
comments by facsimile (FAX) transmission. In commenting, please refer
to file code HSQ-225-P. Comments received timely will be available for
public inspection as they are received, generally beginning
approximately 3 weeks after publication of a document, in Room 309-G of
the Department's offices at 200 Independence Avenue, SW., Washington,
DC, on Monday through Friday of each week from 8:30 a.m. to 5 p.m.
(phone: (202) 690-7890).
For comments that relate to information collection requirements,
mail a copy of comments to:
Office of Information and Regulatory Affairs, Office of Management and
Budget, Room 10235, New Executive Office Building, Washington, DC
[[Page 47535]]
20503, Attn: Allison Herron Eydt, HCFA Desk Officer.
Copies: To order copies of the Federal Register containing this
document, send your request to: New Orders, Superintendent of
Documents, P.O. Box 371954, Pittsburgh, PA 15250-7954. Specify the date
of the issue requested and enclose a check or money order payable to
the Superintendent of Documents, or enclose your Visa or Master Card
number and expiration date. Credit card orders can also be placed by
calling the order desk at (202) 512-1800 or by faxing to (202) 512-
2250. The cost for each copy is $8.00. As an alternative, you can view
and photocopy the Federal Register document at most libraries
designated as Federal Depository Libraries and at many other public and
academic libraries throughout the country that receive the Federal
Register.
FOR FURTHER INFORMATION CONTACT: Rosemary Bakes-Martin, (404) 488-7655,
for questions regarding the criteria for waived test categorization and
the requirements for data submission; and Judy Yost, (410) 786-3531,
for certificate and inspection issues.
SUPPLEMENTARY INFORMATION:
I. Background
Under section 353 of the Public Health Service (PHS) Act (42 U.S.C.
263a), as amended by the Clinical Laboratory Improvement Amendments of
1988 (CLIA), all laboratories that examine human specimens for the
diagnosis, prevention or treatment of any disease or impairment of, or
the assessment of the health of, human beings must meet certain
requirements to perform the examination. On February 28, 1992 (57 FR
7002), we published regulations to implement CLIA at 42 CFR part 493.
Many of the requirements are based on the complexity of the tests
performed. There are currently three test categories: waived, moderate
complexity and high complexity.
In accordance with the law, HHS established a Clinical Laboratory
Improvement Advisory Committee (CLIAC) to advise and make
recommendations on technical and scientific aspects of the regulations.
The CLIAC is composed of individuals involved in the provision of
laboratory services, use of laboratory services, development of
laboratory testing devices or methodologies, and others as approved by
HHS. In addition, HHS has designated four CLIAC subcommittees that
focus on the following areas: cytology; personnel; proficiency testing,
quality control and quality assurance; and test categorization.
We received approximately 16,000 letters from professional
organizations and individuals that provided approximately 71,000
comments in response to publication of the February 28, 1992
regulations. Through this proposed rule, we are responding to the
approximately 1,100 comments concerning the categorization of waived
tests, specifically the subjectiveness of the waived criteria and the
failure of tests to be granted waiver status.
These commenters were responding to our regulations at Sec. 493.15
that merely excerpt the statutory language without elaboration and list
nine tests or examinations that meet the statutory criteria and are
waived. That section further provides that revisions to the list of
waived tests approved by HHS will be published in the Federal Register
in a notice with opportunity for public comment. As currently defined
in the regulation, waived tests are simple laboratory examinations and
procedures that--
(1) Are cleared by the Food and Drug Administration (FDA) for home
use;
(2) Employ methodologies that are so simple and accurate as to
render the likelihood of erroneous results negligible; or
(3) Pose no reasonable risk of harm to the patient if the test is
performed incorrectly.
The specified tests that are listed in the regulation are:
(1) Dipstick or tablet reagent urinalysis (non-automated) for
bilirubin, glucose, hemoglobin, ketone, leukocytes, nitrite, pH,
protein, specific gravity, and urobilinogen;
(2) Fecal occult blood;
(3) Ovulation tests--visual color comparison tests for human
luteinizing hormone;
(4) Urine pregnancy tests--visual color comparison tests;
(5) Erythrocyte sedimentation rate--non-automated;
(6) Hemoglobin--copper sulfate--non-automated;
(7) Blood glucose by glucose monitoring devices cleared by the FDA
specifically for home use;
(8) Spun microhematocrit; and
(9) Hemoglobin by single analyte instruments with self-contained or
component features to perform specimen/reagent interaction, providing
direct measurement and readout.
After evaluating the comments concerning waived tests, we sought
advice in February 1993 from the CLIAC concerning the criteria for
waiver and the process for considering whether specific tests should be
placed in the waived category. The CLIAC agreed that the criteria
should be better defined and recommended that the Centers for Disease
Control and Prevention (CDC) clarify the criteria and process for
categorizing waived tests and suggested that a moratorium be placed on
adding tests to the waived category until the criteria were better
defined. In response to the CLIAC recommendation, CDC initially
established a moratorium on considering tests for waiver while we were
developing the notice of proposed rulemaking to revise the CLIA
regulations for waived categorization.
In response to public concern, on December 19, 1994, the moratorium
was lifted, and CDC notified all manufacturers and producers of
moderate complexity test systems that it will consider for waiver any
test that meets the statutory criteria and for which the manufacturer
or producer applies for waiver in accordance with the CLIA regulations
published February 28, 1992. CDC enclosed guidelines (included in this
rule as proposed test system characteristics and field studies) that
can be used to verify the accuracy and precision of testing devices and
demonstrate that the test meets the statutory criteria for waiver. The
guidelines were included to assist applicants in applying for waiver;
however, all requests will be considered as long as they include valid
scientific studies to verify that the test meets the statutory criteria
for waiver.
II. The Revision Process
Under the statute, waived tests are defined as ``* * * simple
laboratory examinations and procedures that, as determined by the
Secretary, have an insignificant risk of an erroneous result * * *.''
The statute contains additional language to describe the types of
examinations and procedures to be included in the waived category; that
is, tests that have ``* * * been approved by the FDA for home use,
employ methodologies that are so simple and accurate as to render the
likelihood of erroneous results negligible, or the Secretary has
determined pose no reasonable risk of harm to the patient if performed
incorrectly.'' The law also specifies that waived tests are exempt from
the CLIA health and safety standards, including personnel, patient test
management, quality control, proficiency testing, quality assurance,
and routine inspections requirements.
In the preamble of the CLIA regulations published February 28,
1992, in the Federal Register (57 FR 7002), we stated that FDA
clearance of a test for home use could not be used as a sole criterion
for qualifying as a
[[Page 47536]]
waived test. We have continued to review the section of the statute
pertaining to waived tests and believe now that the better view of the
statute is that the waived criteria set out at 42 U.S.C. 263a(d)(3)(A),
(B), and (C) were intended by the Congress to represent the kinds of
tests that are ``simple laboratory examinations and procedures which *
* * have an insignificant risk of an erroneous result.'' Therefore, any
test system cleared by the FDA for home use will, upon receipt of a
request for waiver from the manufacturer, be waived under CLIA.
With regard to the other two criteria for waiver, we believe that a
critical factor to be considered is the implicit statutory mandate that
waived testing be easily performed and provide accurate results.
Therefore, in order for a test to be categorized as waived, it must
both: (1) Be simple; and (2) have an insignificant risk of an erroneous
result. In this rule, we are proposing to clarify the statutory
criteria by specifying performance characteristics and studies designed
to demonstrate that any test system categorized as waived would be
simple, easy to perform, and essentially error-free. We believe that
conformance to these criteria would reduce the possibility of the test
producing an erroneous result and, thus, assist in determining whether
the test system could pose a reasonable risk of harm to a patient if
performed incorrectly.
We are proposing that, to be exempt from CLIA and categorized as
waived, in accordance with the law, all test systems either be cleared
by the FDA for home use or meet the requirements in CLIA to ensure that
the test procedure is simple and not prone to error.
In response to the CLIAC recommendation, CDC developed a protocol
to follow when requesting that tests be placed in the waived category.
The protocol describes basic specifications for verifying that the test
system meets the performance characteristics defined by the criteria.
CDC proposed that, upon request of HHS as specified in Sec. 493.2001,
the CLIAC would review applications for waiver, in accordance with the
waived criteria, and make recommendations to HHS concerning waiver
status.
The proposed clarifications to the criteria for waiver addressing
simplicity and accuracy and the proposed process to follow when
requesting waived categorization were presented to the CLIAC test
categorization subcommittee and subsequently to the full committee. The
CLIAC endorsed the clarifications as well as the process for requesting
waived categorization and recommended that the CLIA regulations be
revised to incorporate the changes.
The CLIAC further recommended that all tests currently on the
waived list be subject to the new clarifications to the criteria to
determine if they should remain in the waived category. The committee
thought that the method previously used to place tests in the waived
category was too subjective and was concerned that some of the tests
may not be sufficiently error-free to justify their continued waived
status.
III. Proposed revisions
Clarified Criteria
In this regulation, we propose to delete Sec. 493.15, which
contains the current criteria for waived tests and a process to
announce revisions to the list. In its place, we would: Clarify the
waived criteria (outlined below), incorporate the clarification into
our regulations at a new Sec. 493.7, and place the remaining
provisions, appropriately revised to reflect the new procedures, at
Sec. 493.9.
Following the recommendation from the CLIAC that we clarify the
criteria for waiver, a number of resources, such as FDA protocols for
defining tests suitable for home use and the National Committee for
Clinical Laboratory Standards protocols for method evaluations, were
used as reference materials. Since one of the main concerns of
commenters on our previous CLIA rulemaking centered around the
subjectiveness and ambiguity of applying the statutory criteria to
categorize the tests as waived, we used information from these sources
to clarify what we mean by ``simple'' and ``not prone to error'' as a
mechanism to define the statutory phrase ``have an insignificant risk
of an erroneous result''. We believe that test systems must possess
certain characteristics that would make them easier to use and they
also must be able to demonstrate a level of accuracy and precision that
would ensure the correct test result is generated regardless of the
user's level of expertise.
Below we have listed test system properties that we believe
illustrate simplicity and ease of use. The test system:
Uses direct unprocessed specimens, requires no specimen
manipulation before analysis or analyst intervention during analysis,
and provides direct readout of results. Quantitative tests must be
fully automated while qualitative tests are limited to simple reagent
impregnated devices that produce only a positive or negative result;
Contains fail-safe mechanisms rendering no results when
the results are outside of the reportable range or when the test system
malfunctions;
Requires no invasive test system troubleshooting, or
electronic or mechanical maintenance; and
Contains instructions written at a comprehension level no
higher than seventh grade. Instructions would have to include step-by-
step system operation and maintenance procedures; reagent preparation
and storage; and calibrator and control preparation, storage, frequency
of assay, and action to be taken if control or calibrator results are
out of range.
We would consider a test for waiver if the test system has these
characteristics. However, we are interested in receiving comments on
alternative test system characteristics or approaches to define the
statutory criterion related to test system simplicity.
The test system characteristics that we are proposing are designed
to limit the amount of operator intervention or interpretive skill
required to perform the test. Limiting operator intervention should
prevent analysts without previous laboratory training or experience
from inadvertently disrupting the analytic process and thus introducing
human error into the testing procedure. The requirement for a fail-safe
mechanism would prevent untrained operators from unknowingly accepting
or utilizing incorrect results. In view of the fact that no previous
training or experience is required before performing waived tests, test
systems in the waived category should not require invasive
troubleshooting or electronic or mechanical maintenance since these
processes rely on the use of interpretive skills to make judgement
decisions. We also believe that an ``easy to use'' test system must
have instructions that are written at a comprehension level that would
provide reasonable assurance that all likely users, regardless of
background, training, or experience, would be able to read and
understand the step-by-step procedures required to correctly perform
testing. We are suggesting that a seventh grade comprehension level is
appropriate to define the waived criteria because waived tests will not
be subject to any personnel requirements and because waived tests must
be simple and capable of providing accurate test results when performed
by non-professional testing personnel. Inasmuch as the considerations
for waiver are similar to those for FDA clearance of home-use products,
and FDA requires that package inserts for
[[Page 47537]]
home-use tests be written at the seventh grade comprehension level, we
are proposing that waived test system instructions be written at the
same comprehension level.
Submission Requirements
To define test systems that are simple, easy to use, and not error
prone, we are proposing that field studies be conducted to
scientifically assess the accuracy and precision of the test. In this
regulation, we are proposing basic criteria for manufacturers and
producers to use in configuring these field studies.
The studies are designed to ensure that the test system generates
consistent results regardless of the environment in which the testing
is performed.
Specifically, we are proposing that these studies:
Evaluate among-operator imprecision;
Evaluate within-site imprecision at a minimum of three
sites; and
Evaluate among-site imprecision.
We are proposing to place no restrictions on the number of study
participants or sites except for specifying that the within-site
studies should be performed at a minimum of three sites. We believe it
is appropriate to provide this flexibility in study design, which
allows applicants to determine the number of participants and sites
that are adequate to produce measures of performance that are both
statistically valid and defensible. Also, the appropriateness of the
number of study participants and sites might vary depending upon the
analyte or test method.
Additionally, in this rule, we are proposing that the studies prove
the test system's clinical reliability by demonstrating accuracy at all
relevant medical decision points. To verify the credibility of the
data, we are proposing in this rule that the number of participants and
sites and the sampling process be adequate to produce measures of
performance that are both statistically valid and defensible (estimates
must support valid confidence limits for all statistical parameters).
We are proposing that the studies be performed at non-laboratory sites
to ensure that all users, professionals as well as lay persons, can
perform waived testing with the same competence. We are proposing that
the study participants have no previous laboratory experience or
training to ensure that individuals used for study purposes have
education, training and experience that is at a level no higher than
that of the lowest trained persons anticipated to perform the test. We
welcome comments and suggestions on the types of studies proposed in
this rule and comments on our proposals for data submission.
Because waived tests would not be subject to any quality control
requirements and we would not routinely conduct inspections of
laboratories performing only waived tests, we propose to require the
laboratory to notify the producer or manufacturer of the test system of
any performance that does not meet the specifications as outlined in
the test system instructions and would require the producer or
manufacturer to include in the test system instructions the address and
phone number of the person to contact. If the manufacturer or producer
of the test system does not resolve the problem, we would require the
laboratory to notify PHS of the problem.
We also would require that test system instructions include a
statement to inform the laboratory that if the laboratory modifies or
alters the test system instructions in any way (for example, changes in
specimen type or sample amount), the test no longer meets the
requirements for waiver and is considered to be high complexity and,
thus, must meet all the applicable CLIA requirements in 42 CFR part
493.
Review Process
To ensure that tests categorized as waived are simple, accurate and
essentially error-free, we would require that waived tests meet the
clarified criteria. Once the final rule responding to the comments
received to this proposed rule is published, we plan to evaluate
requests for waiver, in accordance with the data submittal requirements
and process for requesting waived categorization that would be included
under Sec. 493.7, and to apply the new requirements to currently waived
tests. However, it should be noted that when the CLIA regulations are
revised to incorporate changes to the waiver process, we expect that
the review process for waived categorization of devices having similar
test methodologies could be simplified. For example, if a test system
employs the same methodology as a device that has been granted waiver
in accordance with the final regulations, submission of studies showing
accuracy and precision equivalency between the applicant test system
and the waived test should be sufficient. These studies must reflect
data that are adequate to produce measures of performance that are
statistically valid and defensible and estimates must support valid
confidence limits for all parameters.
In this rule, we are proposing that, after waiver has been granted,
any change or modification by the maunfacturer or producer to the test
system that could affect the test accuracy or reliability (that is,
procedural changes that would now require operator intervention during
the analytic process or method changes that require performance studies
to reevaluate test validity) be resubmitted for evaluation and review.
Changes to a test system that would not affect test performance, such
as those made to improve component appearance or durability, would not
have to be resubmitted.
The Department's purpose in issuing this proposed rule is to
clarify the criteria for determining which tests should be waived. In
this regard, there may be alternative formulations that would result in
more, or fewer, waived tests. In this proposed rule, we specifically
request comments concerning:
Which proposed criteria might be modified (and how), as
well as comments in support of the provisions contained in this
proposed rule;
The impact on patient access to care if these criteria are
finalized;
The health implications of any recommended changes,
including not only the possibility of erroneous test results but also
likely effects on patient health if additional testing is discouraged
or encouraged (for example, by providing such testing in a doctor's
office); and
The potential that these criteria may or may not have for
driving new technology toward more safe and accurate testing.
In addition, we are interested in receiving comments and
suggestions about how we might include in the waived categorization
process considerations related to the benefits to the public of
categorizing tests as waived. Although the statute does not specify
this as a criterion for waiver, we recognize this as a significant
factor affecting access to care.
After the comments to this rule are evaluated and a final rule is
published, we plan to follow the CLIAC recommendation that PHS
reevaluate tests that were previously categorized as waived against any
new regulatory criteria. If changes to the previously waived tests are
necessary, we plan to publish a notice in the Federal Register
soliciting comments on the proposed changes.
Waived Test List
In this rule, we propose to delete the generic list of waived tests
from
[[Page 47538]]
Sec. 493.15. However, at Sec. 493.7(c)(3), we would retain the
provision, currently at Sec. 493.15(d), to publish the names of the
tests that are waived in a Federal Register notice with an opportunity
for public comment. In addition, for consistency with the test
categorization provisions in Sec. 493.17(c)(1)(ii), we would make
waived categorization effective on the date of notification to the
applicant. Any entity that is notified of approval of its waiver
application must be aware, however, that we may rescind this waiver
approval and recategorize the test should comments we receive convince
us that our initial waiver decision was inappropriate.
Summary of Proposed Changes to the Regulation
We propose to remove Sec. 493.15 in its entirety. The criteria
currently in Sec. 493.15(b) for determining whether a given test can be
categorized as waived would now be in a new Sec. 493.7 and in greater
detail. The requirements applicable to certificate of waiver
laboratories (formerly at Sec. 493.15(e)) would be expanded and placed
in a new Sec. 493.9.
In Sec. 493.9, we would continue to require laboratories to follow
the manufacturer's or producer's instructions when performing waived
tests and to meet the requirements in subpart B of part 493. In line
with the clarifications provided to the statutory criteria for
categorizing tests as waived, we also would state that if a laboratory
does not follow the manufacturer's or producer's instructions or makes
a modification in the test system, the laboratory would no longer meet
the requirements for certificate of waiver and the modified test, as
performed by the laboratory, would be considered high complexity until
otherwise categorized. If a laboratory or manufacturer desires official
categorization of the modified test, it must submit a written request
to PHS. Categorization of the modified product should occur within 30
days after PHS receives the request. In addition, laboratories would be
required to report to PHS any performance problems not resolved by the
producer or manufacturer of the test.
We would also make technical conforming changes to the following
sections and headings because of our revisions concerning waived tests:
Secs. 493.2; 493.20(c); 493.25(d); 493.35 (a) and (d); 493.37(b)(1) and
(g); 493.39 introductory paragraph and paragraph (a); 493.45 (a)(2) and
(a)(3); 493.47(a)(2); 493.49 introductory paragraph and (b)(2)(iv);
493.53(a); 493.1775(b)(4)(iii) through (v), and (c).
IV. Response to Comments
Because of the large number of items of correspondence we normally
receive on Federal Register documents published for comment, we are not
able to acknowledge or respond to them individually. We will consider
all comments we receive by the date and time specified in the DATES
section of this preamble, and, if we proceed with a subsequent
document, we will respond to the comments in the preamble to that
document.
V. Collection of Information Requirements
The proposed rule contains information collections that are subject
to review by the Office of Management and Budget (OMB) under the
Paperwork Reduction Act of 1980. The title, description, and respondent
description of the information collection requirements are shown below
with an estimate of the annual reporting and recordkeeping burden.
Included in the estimate is the time for reviewing instructions,
searching existing data sources, gathering and maintaining the data
needed, and completing and reviewing the collection of information.
Section 493.7: This section outlines the criteria a manufacturer
must follow in order to have a test considered to be a ``waived'' test.
These include but are not limited to test system characteristics,
instructions, field studies and the evaluation of data.
Section 493.9: This section outlines the requirements for
laboratories performing waived tests. These include following the
manufacturers' instructions and reporting to PHS performance problems
not resolved by the manufacturer.
Sections 493.35, 493.39, 493.49, 493.53: Sections 493.35 through
493.63 are currently approved under OMB approval number 0938-0612 with
an expiration date of February 28, 1998. The information is gathered on
form number HCFA-R-26. These sections outline the requirements for a
laboratory to follow to submit application forms for CLIA
certification. The requirements include laboratory notification to HHS
of changes to the types of tests performed or changes in ownership,
name, location or director.
Section 493.1775: Section 493.1775 is currently approved under OMB
approval number 0938-0612 with an expiration date of February 28, 1998.
This section sets forth conditions and standards for inspection of
laboratories. The burden associated with inspections consists of
retrieving the records and documentation requested by the inspector,
participating in the entrance and exit interviews, responding to the
statement of deficiencies that may result from the inspection and
documenting any corrective actions taken that are appropriate to the
plan of correction for the deficiencies cited.
When OMB approves those provisions not currently approved we will
publish a notice in the Federal Register to that affect.
Description of Respondents
Section 493.7: Small businesses or organizations, businesses or
other for profit, non-profit institutions, who manufacture laboratory
tests.
Sections 493.9, 493.35, 493.39, 493.49, 493.53; 493.1775: Small
businesses or organizations, businesses or other for profit, non-profit
institutions, state and local governments, federal agencies.
Estimated Annual Reporting and Recordkeeping Burden
----------------------------------------------------------------------------------------------------------------
Annual No. Annual
CFR sections of Annual Average burden per burden per
responses frequency response hours
----------------------------------------------------------------------------------------------------------------
493.35, 493.39, 493.49, 493.53..................... 28,700 1 .25 hr.............. 7,175
493.1775........................................... 1,280(a) 1 4 hrs............... 2,560
493.7.............................................. 20 1 168 hrs............. 3,360
493.9.............................................. <20>b) (b)................. (b)
----------------------------------------------------------------------------------------------------------------
a Based on receiving complaints on 2 percent of waived laboratories (64,000) resulting in the survey of 1,280
waived laboratories with complaints in a two year period.
b Laboratories are responsible for following manufacturers' instructions when performing waived tests. Whenever
a problem is encountered by the laboratory that is not resolved by the manufacturer, the laboratory must
notify PHS. This should be an infrequent occurrence (manufacturers generally resolve problems identified by
laboratories).
[[Page 47539]]
The agency has submitted a copy of the proposed rule to OMB for its
review of these information collections. Interested persons are invited
to send comments regarding this burden estimate or any other aspect of
this collection of information, including any of the following
subjects: (1) The necessity and utility of the proposed information
collection for the proper performance of the agency's functions; (2)
the accuracy of the estimated burden; (3) ways to enhance the quality,
utility, and clarity of the information to be collected; and (4) the
use of automated collection techniques or other forms of information
technology to minimize the information collection burden. Comments
should be sent to HCFA, HSQB, MPAS, C2-26-17, 7500 Security Boulevard,
Baltimore, Maryland 21244-1850 and to the OMB official whose name
appears in the ADDRESSES section of this preamble.
VI. Regulatory Impact Statement
We generally prepare a regulatory flexibility analysis that is
consistent with the Regulatory Flexibility Act (RFA) (5 U.S.C. 601
through 612) unless the Secretary certifies that a rule would not have
a significant economic impact on a substantial number of small
entities. For purposes of the RFA, all laboratories and manufacturers
and producers of laboratory test systems are considered to be small
entities. Individuals and States are not included in the definition of
a small entity.
Also, section 1102(b) of the Act requires the Secretary to prepare
a regulatory impact analysis if a rule may have a significant impact on
the operations of a substantial number of small rural hospitals. This
analysis must conform to the provisions of section 603 of the RFA. For
purposes of section 1102(b) of the Act, we define a small rural
hospital as a hospital that is located outside of a Metropolitan
Statistical Area and has fewer than 50 beds.
As a result of our evaluation of comments received on the test
categorization portion of the February 28, 1992 regulations
implementing CLIA and as a result of additional consultation with the
CLIAC, we are proposing to clarify the criteria and process used to
categorize laboratory tests as waived. Manufacturers and producers of
laboratory test systems specifically suggested that the types of
information and data to be submitted when requesting waived
categorization be more clearly defined in order to ensure that the
criteria are applied accurately and uniformly to all laboratory tests.
The proposed expansion of the waived criteria and development of a
process protocol would provide for consistent application of detailed
standards in order to ensure that tests categorized as waived are
either cleared by the FDA for home use or are simple to use, produce
accurate results when testing is performed, and preclude any reasonable
risk of harm to patients as a result of testing errors. Of course,
manufacturers and producers would be required to submit specific
information and data demonstrating that their test system meets the
criteria for waived categorization. In some cases, manufacturers or
producers of test systems might have to conduct additional studies to
obtain the information required; however, much of the data is similar
to that currently required by the FDA for clearance of products. In
accordance with the law, this rule would provide that any test system
cleared by the FDA for home use will, upon application by the
manufacturer, be waived from CLIA. We anticipate that manufacturers and
producers ultimately will benefit in the form of increased sales and
distribution of tests categorized as waived.
Currently, almost one-half of all laboratories hold certificates of
waiver. These laboratories would obviously benefit from an improved
test categorization process that yields more waived tests. Any increase
in the number of waived tests would benefit laboratories by reducing
the regulatory burden, since laboratories limiting their services to
waived test performance are not subject to the CLIA health and safety
standards (including proficiency testing, quality control, personnel,
recordkeeping and quality assurance requirements). Certificate of
waiver laboratories are required only to register and follow
manufacturers' and producers' instructions for test performance. In
addition, increasing the number of waived tests would enable
laboratories to provide an expanded test menu without incurring the
higher fees associated with a regular CLIA certificate. The
availability of an expanded test menu at less cost also may encourage
new entities to begin providing services, thereby increasing access to
health care, particularly in underserved and rural areas. Consumers of
laboratory services would benefit from an enhanced range of laboratory
services that have been determined to be safe and produce accurate
results.
We have developed these clarifications to the waived criteria in an
effort to improve the process of approving tests for waiver. We believe
that using the better defined criteria would result in more tests being
waived if for no other reason than because the improved waiver process
should drive the technology toward simpler tests that would then be
widely available (because of waived status). However, we realize that
the number of tests waived could vary depending upon the revisions to
the waiver process. Depending on how many more or fewer tests receive a
waiver, there could be significant effects on patient health (due to
more or less patient access to testing, as well as more or fewer test
errors) and impact on manufacturers, producers and laboratories. We
request comments on alternatives that might produce higher benefits or
lower costs, taking into account all effects. We particularly solicit
comments that can provide quantitative estimates of likely effects on
patient health resulting from different waived criteria and, hence,
waived tests.
As indicated above, we believe that over time the effect of this
rule will be to expand the universe of waived tests, to the benefit of
patients, laboratories, manufacturers, and producers. However, we are
unable to quantify these likely long run effects because they depend on
market decisions, research results, and technological change that
cannot be predicted.
In the short run, we would not expect substantial effects.
Currently there are nine waived tests and about 250 individual test
systems or products representing nine analytes or specific types of
procedures that have been approved as waived tests. Assuming that the
final rule does not depart substantially from the proposed criteria,
the great majority of individual tests would continue to be eligible
for the waiver category. We expect that laboratories would continue to
have a wide range of products/test systems available and would
therefore not lose waiver status. At most, only a few products might
not meet the clarified waived criteria and any such test system's
manufacturer or producer would have the option of improving test
accuracy.
This proposed rule would clarify the process and criteria for
categorizing waived tests and possibly result in changes in the list of
waived tests. Proper realignment of the fee schedule, if necessary,
would follow implementation of this rule.
For these reasons, we are not preparing analyses for either the RFA
or section 1102(b) of the Act because we have determined, and the
Secretary certifies that this proposed rule will not have a significant
economic impact on a substantial number of small entities or
[[Page 47540]]
the operations of a substantial number of small rural hospitals. We do
request comments, however, on possible adverse effects on affected
entities and will consider these carefully in formulating the final
rule.
In accordance with the provisions of Executive Order 12866, this
regulation was reviewed by the Office of Management and Budget.
List of Subjects in 42 CFR Part 493
Grant programs-health, Health facilities, Laboratories, Medicaid,
Medicare, Reporting and recordkeeping requirements.
42 CFR part 493 would be amended as set forth below:
PART 493--LABORATORY REQUIREMENTS
1. The authority citation for part 493 continues to read as
follows:
Authority: Sec. 353 of the Public Health Service Act, secs.
1102, 1861(e), the sentence following 1861(s)(11), 1861(s)(12),
1861(s)(13), 1861(s)(14), 1861(s)(15), and 1861(s)(16) of the Social
Security Act (42 U.S.C. 263a, 1302, 1395x(e), the sentence following
1395x(s)(11), 1395x(s)(12), 1395x(s)(13), 1395x(s)(14),
1395x(s)(15), and 1395x(s)(16)).
2. In Sec. 493.2, in the definition of ``CLIA certificate'' the
introductory text is republished and paragraph (2) and (5) are revised
to read as follows:
Sec. 493.2 Definitions.
* * * * *
CLIA certificate means any of the following types of certificates
issued by HCFA or its agent:
* * * * *
(2) Certificate for provider-performed microscopy (PPM) procedures
means a certificate issued or reissued before the expiration date,
pending an appeal, in accordance with Sec. 493.47, to a laboratory in
which a physician, midlevel practitioner or dentist performs no tests
other than PPM procedures and, if desired, tests approved by PHS as
waived under Sec. 493.7.
* * * * *
(5) Certificate of waiver means a certificate issued or reissued
before the expiration date, pending an appeal, in accordance with
Sec. 493.37, to a laboratory to perform only the tests approved by PHS
as waived under Sec. 493.7.
* * * * *
3. A new Sec. 493.7 is added to read as follows:
Sec. 493.7 Waived tests.
(a) Requirement. For a test to be included in the waived category,
the test system must meet the descriptive criteria specified in
paragraph (b) of this section.
(b) Criteria. Test systems must be simple laboratory examinations
and procedures that have an insignificant risk of an erroneous result.
Test systems cleared by the FDA for home use meet the criteria
specified in this section and will be approved for waiver following
submission of the manufacturer's or producer's request for waiver
approval.
(1) For quantitative tests, methods must be simple (easy to use)
and accurate as evidenced by the following items:
(i) Test systems that have the following characteristics:
(A) Are fully automated or self-contained.
(B) Use only direct unprocessed specimens.
(C) Require no specimen manipulation before the analytic phase of
operation.
(D) Require no operator intervention during the analytic phase.
(E) Provide a direct readout of results; that is, require no
calculations or conversions.
(F) Contain fail-safe mechanisms that render no result when the
test system malfunctions and initiate fail-safe mechanisms rendering no
test result when the result is outside the reportable range.
(G) Require no invasive test system troubleshooting to be performed
by testing personnel and include no electronic or mechanical
maintenance to be performed by testing personnel.
(ii) Test system instructions that are written at a comprehension
level no higher than the seventh grade (as demonstrated by accepted
academic standards) and that address the following items:
(A) Analytical skills required of personnel performing the test.
(B) Attributes or limitations of the physical environment or
conditions for test performance.
(C) Requirements for specimen collection, handling, storage and
preservation.
(D) Reportable range for patient results.
(E) Reference range (normal values).
(F) Step-by-step protocols that include, as appropriate, the
following items:
(1) Instrument or test system operation and test performance
instructions.
(2) Test system maintenance procedures.
(3) Preparation and storage of reagents, calibrators, controls or
other materials used in testing.
(4) Control procedures, including the type of materials, suggested
concentrations, and frequency of assay.
(5) Calibration procedures, including the number and type of
materials and frequency of assay.
(6) Acceptable ranges for any control or calibration material
included with the test system.
(7) Action to be taken when calibration or control results do not
meet the acceptable range of values.
(8) Description of course of action to be taken when the test
system becomes inoperable.
(iii) Field studies that meet the following criteria:
(A) Are performed at nonlaboratory sites.
(B) Include study participants who have no previous laboratory
experience or training. The number of participants and sites selected
must be adequate to produce measures of performance that are both
statistically valid and defensible.
(C) Demonstrate that the manufacturer's or producer's written
instructions are the only protocols required to perform the test
accurately and reliably.
(D) Demonstrate that the test system produces accurate results
under the testing conditions and within the physical environment
specifications defined in the test system instructions.
(E) For those tests that employ calibration, demonstrate that
calibration is stable over the calibration frequency interval or that a
fail-safe mechanism rendering no result is initiated when the test
system is out of calibration.
(iv) Data from field studies that meet the following criteria:
(A) Are generated from protocols that address the points described
in paragraph (b)(1)(iii) of this section.
(B) Are adequate to produce measures of performance that are both
statistically valid and defensible (estimates must support valid
confidence limits for all statistical parameters).
(C) Evaluate performance at all medical decision points and
relevant upper and lower limits of the reportable range using at least
three concentrations of the analyte being tested.
(D) Evaluate among-operator imprecision using test results of all
study participants.
(E) Evaluate within-site imprecision using test results generated
at each site by an adequate number of participants to produce measures
of performance that are statistically valid and defensible. Testing
must be performed at a minimum of three independent study sites.
(F) Evaluate among-site imprecision at an adequate number of sites
to produce
[[Page 47541]]
measures of performance that are statistically valid and defensible.
(G) Demonstrate that the total amount of imprecision, which
includes all components contributing to imprecision as demonstrated by
studies described in paragraphs (b)(1)(iv) (D), (E) and (F) of this
section, is less than one-fourth of the reference range for the analyte
divided by the mean of the reference interval.
(v) Method accuracy studies demonstrating that the test system is
not affected by systematic error when--
(A) Using reference materials assayed by study participants that
produce data that prove there is no statistically significant
difference between the test results and the value of the reference
materials;
(B) Using patient samples instead of reference materials, proving
that there is no statistically significant difference between test
results obtained on patient and reference materials due to the effects
of the sample matrix; and
(C) Using patient samples containing substances that commonly cause
interference, confirming there is no introduction of error due to the
presence of these substances.
(2) For qualitative tests, methods must be simple (easy to use)
and accurate as evidenced by the following items:
(i) Test systems that have the following characteristics:
(A) Use only direct unprocessed specimens.
(B) Require no specimen manipulation before performing the testing
procedure.
(C) Contain no procedural steps beyond adding a sample to a reagent
impregnated device.
(D) Require no specimen manipulation during the procedure.
(E) Require a well-defined distinct endpoint that is limited to
positive or negative interpretation.
(F) Contain fail-safe mechanisms that render no result when the
test system malfunctions.
(ii) Test system instructions that are written at a comprehension
level no higher than the seventh grade (as demonstrated by accepted
academic standards) and that address the following items, as
appropriate:
(A) Analytical skills required of personnel performing the test.
(B) Attributes or limitations of the physical environment or
conditions for test performance:
(C) Requirements for specimen collection, handling, storage and
preservation.
(D) Patient result reporting.
(E) Reference range (normal values).
(F) Step-by-step protocols that include, as appropriate, the
following items:
(1) Test performance instructions.
(2) Preparation and storage of reagents, calibrators, controls or
other materials used in testing.
(3) Control procedures, including the type of materials and
frequency of assay.
(4) Calibration procedures, including the number and type of
materials and frequency of assay.
(5) Acceptable ranges for any control or calibration material
included with the test system.
(6) Action to be taken when calibration or control results do not
meet the acceptable range of values.
(7) The correct interpretation of test endpoints.
(8) Description of course of action to be taken when test endpoints
cannot be determined.
(iii) Field studies that meet the following requirements:
(A) Are performed at nonlaboratory sites.
(B) Include study participants who have no previous laboratory
experience or training. The number of participants and sites selected
must be adequate to produce measures of performance that are both
statistically valid and defensible.
(C) Demonstrate that the manufacturer's or producer's written
instructions are the only protocols required to perform the test
accurately and reliably.
(D) Demonstrate that the test system produces accurate results
under the testing conditions and within the physical environment
specifications defined in the test system instructions.
(E) For those tests that employ calibration, demonstrate that
calibration is stable over the calibration frequency interval or that a
fail-safe mechanism rendering no result is initiated when the test
system is out of calibration.
(iv) Data from field studies that meet the following requirements:
(A) Are generated from protocols that address the points described
in paragraph (b)(2)(iii) of this section.
(B) Are adequate to produce measures of performance that are both
statistically valid and defensible.
(C) Confirm that study participants are able to read the test
endpoint with the same precision as laboratory professionals.
(D) Confirm that the performance of study participants is
essentially the same as laboratory professionals when testing samples
at or near the cutoff and at sufficient distance above and below the
cutoff to confirm precision at all analytical decision points.
(E) Demonstrate minimal among-operator imprecision using results of
all study participants.
(F) Demonstrate minimal within-site imprecision using test results
generated at each site by an adequate number of participants to produce
measures of performance that are statistically valid and defensible.
Testing must be performed at a minimum of three independent study
sites.
(G) Using results generated by study participants, on aliquots of a
single testing material, demonstrate minimal among-site imprecision at
an adequate number of sites to produce measures of performance that are
statistically valid and defensible.
(v) Method accuracy studies demonstrating that there is no
statistically significant difference between observed values and
expected values at the cutoff point when--
(A) The test values are compared to a quantitative result such as
the value of a reference material or the presence or absence of a
particular biologic component;
(B) Confirming that there are no significant equivocal test results
on either side of the cutoff;
(C) Comparing results between study participants and laboratory
professionals on samples with values at the cutoff;
(D) The test is performed on patient samples instead of reference
materials, confirming there is no introduction of error due to sample
matrix; and
(E) Samples contain substances that commonly cause interference,
confirming there is no introduction of error due to these substances.
(c) Waiver process--(1) Process for requesting waived status. (i)
Requests for waiver of tests must be submitted to PHS.
(ii) PHS reviews requests for waiver that meet the criteria
specified in paragraph (b) of this section and the submission
requirements under paragraph (c)(2) of this section.
(iii) The Clinical Laboratory Improvement Advisory Committee
(CLIAC), as specified in subpart T of this part, conducts reviews upon
request of HHS and makes recommendations to HHS concerning the waiver
of tests.
(iv) Any change or modification to a test system by the
manufacturer or producer that could affect the accuracy or reliability
of the waived test must be resubmitted to PHS for evaluation and
review. Until this review is completed and status is determined, the
modified test is considered uncategorized and, in accordance with
Sec. 493.17(c)(4), is considered high complexity.
[[Page 47542]]
(v) A request for reconsideration of a test denied waived status is
accepted for review if the request is based on information not
previously submitted.
(2) Submission requirements--(i) Requests for waiver must meet the
criteria described in paragraph (b) of this section. In the event that
a request does not include complete information, the request is not
reviewed and the manufacturer or producer of the test system is
notified.
(ii) Data collection protocols and data submitted must be complete
and data submitted must be statistically valid and meet the criteria
described under paragraph (b) of this section.
(iii) Test system instructions must be complete and must include,
as applicable, the items defined in paragraph (b)(1)(ii) of this
section for quantitative tests and under paragraph (b)(2)(ii) of this
section for qualitative tests. In addition, test system instructions
must include the following statements:
(A) ``Any modification by the laboratory to the test system or the
PHS-approved test system instructions will result in the test no longer
meeting the requirements for waived categorization. A modified test is
considered to be high complexity and is subject to all applicable CLIA
requirements contained in 42 CFR part 493.''
(B) ``The laboratory must notify the manufacturer or producer of
this test system of any performance, perceived or validated, that does
not meet the performance specifications as outlined in the
instructions.'' The name, address and phone number(s) of the
manufacturer's or producer's contact person(s) must follow this
statement.
(iv) Using the criteria specified in paragraph (b) of this
section, each test categorized as waived before [date of publication of
final rule] will be reevaluated by PHS.
(3) Notification of decision--(i) PHS determines whether a
laboratory test meets the criteria listed under paragraph (b) of this
section for a waived test.
(ii) PHS notifies the applicant of the waived categorization
determination, whether denied or granted.
(iii) Waived categorization is effective as of the date of
notification to the applicant.
(iv) PHS publishes additions and revisions periodically to the
tests categorized as waived in the Federal Register in a notice with an
opportunity for public comment. PHS reserves the right to reevaluate
and recategorize a test based upon the comments it receives in response
to the Federal Register notice.
4. A new Sec. 493.9 is added to read as follows:
Sec. 493.9 Laboratories performing waived tests.
(a) A laboratory may qualify for a certificate of waiver under
section 353 of the PHS Act if it restricts its test performance to one
or more tests approved by PHS as waived under Sec. 493.7.
(b) Laboratories issued a certificate of waiver must meet the
following requirements:
(1) Follow the manufacturer's or producer's instructions for
performing the test. If a laboratory does not follow the manufacturer's
or producer's test system instructions, the laboratory no longer meets
the requirements for a certificate of waiver and the modified test, as
performed by the laboratory, is considered high complexity until
otherwise categorized.
(2) Report to PHS any performance problems not resolved by the
manufacturer or producer of the test.
(3) Meet the requirements in subpart B of this part.
Sec. 493.15 [Removed]
5. Section 493.15 is removed.
6. In Sec. 493.20, paragraph (c) is revised to read as follows:
Sec. 492.20 Laboratories performing tests of moderate complexity.
* * * * *
(c) If the laboratory also performs waived tests, compliance with
subparts H, J, K, M, and P of this part is not applicable to the waived
tests. However, the laboratory must comply with the requirements in
Secs. 493.9(b) and 493.1775.
7. In Sec. 493.25 paragraph (d) is revised to read as follows:
Sec. 493.25 Laboratories performing tests of high complexity.
* * * * *
(d) If the laboratory also performs waived tests, the requirements
of subparts H, J, K, M, and P are not applicable to the waived tests.
However, the laboratory must comply with the requirements in
Secs. 493.9(b) and 493.1775.
8. In Sec. 493.35, paragraphs (a) and (d) are revised to read as
follows:
Sec. 493.35 Application for a certificate of waiver.
(a) Filing of application. Except as specified in paragraph (b) of
this section, a laboratory performing only one or more tests approved
by PHS as waived under Sec. 493.7 must file a separate application for
each laboratory location.
* * * * *
(d) Access requirements. Laboratories that perform one or more
tests approved by PHS as waived under Sec. 493.7 and no other tests
must meet the following conditions:
(1) Make records available and submit reports to HHS as HHS may
reasonably require to determine compliance with this section and
Sec. 493.9(b).
(2) Agree to permit announced and unannounced inspections by HHS in
accordance with subpart Q of this part under the following
circumstances:
(i) When HHS has substantive reason to believe that the laboratory
is being operated in a manner that constitutes an imminent and serious
risk to human health.
(ii) To evaluate complaints from the public.
(iii) On a random basis to determine whether the laboratory is
performing tests not approved by PHS as waived under Sec. 493.7.
(iv) To collect information regarding the appropriateness of tests
approved by PHS as waived under Sec. 493.7.
* * * * *
9. In Sec. 493.37, the introductory text of paragraph (b) is
republished and paragraphs (b)(1) and (g) are revised to read as
follows:
Sec. 493.37 Requirements for a certificate of waiver.
* * * * *
(b) Laboratories issued a certificate of waiver--(1) Are subject to
the requirements of this subpart and Sec. 493.9(b); and
* * * * *
(g) A laboratory with a certificate of waiver that wishes to
perform examinations or tests not approved by PHS as waived under
Sec. 493.7 must meet the requirements set forth in subpart C or subpart
D of this part, as applicable.
10. In Sec. 493.39, the introductory text and paragraph (a) are
revised to read as follows:
Sec. 493.39 Notification requirements for laboratories issued a
certificate of waiver.
Laboratories performing one or more tests approved by PHS as waived
under Sec. 493.7 and no others must notify HHS or its designee--
(a) Before performing and reporting results for any test not
approved by PHS as a waived under Sec. 493.7 for which the laboratory
does not have the appropriate certificate as required in subpart C or
subpart D of this part, as applicable; and
* * * * *
11. In Sec. 493.45, the introductory text of paragraph (a) is
republished,
[[Page 47543]]
paragraph (a)(3) is removed, and paragraph (a)(2) is revised to read as
follows:
Sec. 493.45 Requirements for a registration certificate.
* * * * *
(a) A registration certificate is required--
* * * * *
(2) For all laboratories that have been issued a certificate of
waiver or certificate for PPM procedures that intend to perform tests
of moderate or high complexity, or both, in addition to those tests
approved by PHS as waived under Sec. 493.7 or specified as PPM
procedures.
* * * * *
12. In Sec. 493.47, paragraph (a) is revised to read as follows:
Sec. 493.47 Requirements for a certificate for provider-performed
microscopy (PPM) procedures.
(a) A certificate for PPM procedures is required--
(1) Initially for all laboratories performing test procedures
specified as PPM procedures; and
(2) For all certificate of waiver laboratories that intend to
perform only test procedures specified as PPM procedures in addition to
those tests approved by PHS as waived under Sec. 493.7.
* * * * *
13. In Sec. 493.49, the introductory text of paragraphs (b) and
(b)(2) are republished and the introductory text of the section and
paragraph (b)(2)(iv) are revised to read as follows:
Sec. 493.49 Requirements for a certificate of compliance.
A certificate of compliance may include any combination of tests
categorized as high complexity or moderate complexity or approved by
PHS as waived under Sec. 493.7. Moderate complexity tests may include
those specified as PPM procedures.
* * * * *
(b) Laboratories issued a certificate of compliance--
* * * * *
(2) Must permit announced or unannounced inspections by HHS in
accordance with subpart Q of this part--
* * * * *
(iv) To collect information regarding the appropriateness of tests
approved by PHS as waived under Sec. 493.7 or tests categorized as
moderate complexity (including the subcategory) or high complexity.
* * * * *
14. In Sec. 493.53, the introductory text is republished and
paragraph (a) is revised to read as follows:
Sec. 493.53 Notification requirements for laboratories issued a
certificate for provider-performed microscopy (PPM) procedures.
Laboratories issued a certificate for PPM procedures must notify
HHS or its designee--
(a) Before performing and reporting results for any test of
moderate or high complexity, or both, in addition to tests specified as
PPM procedures or any test or examination that is not approved by PHS
as waived under Sec. 493.7 for which it does not have a registration
certificate as required in subpart C or subpart D, as applicable, of
this part; and
* * * * *
15. In Sec. 493.1775, the introductory text of paragraphs (b) and
(b)(4) is republished and paragraph (b)(4)(iv) is redesignated as
(b)(4)(v), a new (b)(4)(iv) is added, and paragraphs (b)(4)(iii) and
(c) are revised to read as follows:
Sec. 493.1775 Condition: Inspection of laboratories issued a
certificate of waiver.
* * * * *
(b) The laboratory may be required, as part of this inspection,
to--
* * * * *
(4) Permit HHS or its designee upon request to review all
information and data necessary to--
* * * * *
(iii) Determine whether the laboratory is performing tests not
approved by PHS as waived under Sec. 493.7;
(iv) Determine whether the laboratory is performing the test in
accordance with the manufacturer's or producer's instructions; and
* * * * *
(c) The laboratory must provide upon reasonable request all
information and data needed by HHS or its designee to make a
determination of compliance with the requirements of part 493.
Requirements for the purposes of this section are located in subparts A
and B or subpart D, if applicable, of this part.
* * * * *
Authority: Sec. 353 of the Public Health Service Act (42 U.S.C.
263a).
Dated: May 18, 1995.
Philip R. Lee,
Assistant Secretary for Health.
Bruce C. Vladeck,
Administrator, Health Care Financing Administration.
Dated: June 2, 1995.
Donna E. Shalala,
Secretary.
[FR Doc. 95-22378 Filed 9-12-95; 8:45 am]
BILLING CODE 4120-01-P
