[Federal Register Volume 65, Number 141 (Friday, July 21, 2000)]
[Notices]
[Pages 45384-45385]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-18456]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 00N-1394]


Medical Devices; CLIA Waiver Criteria; Public Workshop

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of public workshop.

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    The Food and Drug Administration (FDA) is announcing a public 
workshop to review the criteria used to determine whether specific 
laboratory tests are waived from certain requirements of the Clinical 
Laboratory Improvement Amendments of 1988 (CLIA). The purpose of the 
public workshop is to obtain additional comments on the criteria and 
process the agency should use to determine when a particular test is 
waived.
    Date and Time: The public workshop will be held on August 14 and 
15, 2000, from 9 a.m. to 5 p.m. each day.
    Location: The public workshop will be held at the Washingtonian 
Center Marriott Hotel, 9751 Washingtonian Blvd., Gaithersburg, MD 
20878, 301-590-0044.
    Contact: Clara A. Sliva, Center for Devices and Radiological Health 
(HFZ-440), Food and Drug Administration, 2098 Gaither Rd., Rockville, 
MD 20850, 301-827-0496, FAX 301-827-1401, e-mail: [email protected].
    Registration and Requests for Oral Presentations: Send registration 
information (including name, title, firm name, address, telephone, and 
fax number), written material, and requests to make oral presentations 
to the contact person by August 4, 2000. Submit written comments to the 
Dockets Management Branch (HFA-305), Food and Drug Administration, 5630 
Fishers Lane, rm. 1061, Rockville, MD 20850, by September 14, 2000.
    If you need special accommodations due to a disability, please 
contact Clara A. Sliva at least 7 days in advance of the meeting.

SUPPLEMENTARY INFORMATION:

A. Background

    CLIA specifies that laboratory requirements be based on the 
complexity of the tests performed and establishes criteria for 
categorizing a test as waived. Responsibility for determining whether a 
particular test is waived was transferred from the Centers for Disease 
Control and Prevention (CDC) to FDA on January 31, 2000. In the Federal 
Register of September 13, 1995 (60 FR 47534), CDC published proposed 
clarifications to the statutory criteria for waiver. CDC based the 
proposal on guidelines CDC developed to assist the manufacturers in 
submitting waiver requests. The proposed regulations recommend a 
methodology for demonstrating that a test system proposed for waived 
status be so ``simple'' and ``accurate'' as to render the likelihood of 
erroneous results negligible. The Food and Drug Administration 
Modernization Act of 1997 (FDAMA) (Public Law No. 105-115) modified 42 
U.S.C. 263a (d)(3) of the Public Health Service Act by adding the 
phrase ``by the user'' to clarify that waived tests include those which 
employ methodologies that are so simple and accurate as to render the 
likelihood of erroneous results by the user negligible. FDAMA also 
clarified that waived tests include those that are cleared by FDA for 
home use.
    Following transfer of responsibility for waiver determinations from 
CDC to FDA, manufacturers now submit premarket applications for 
products and requests for complexity categorization of these products 
to one agency. FDA is currently following the same policies applied by 
CDC to the waiver criteria prior to the transfer; FDA is performing the 
``same work'' the ``same way.'' Under the current process, FDA 
generally will waive: (1) Any test system that meets the specifications 
described in the guidelines published in the proposed rule of September 
13, 1995, and (2) any test system that provides scientifically valid 
data verifying that the statutory criteria for waiver have been met.

[[Page 45385]]

    FDA believes it needs additional information from stakeholders to 
effectively implement its new responsibilities with respect to waiver 
decisions. In particular, the agency needs to decide whether to 
continue to apply the current criteria, finalize the proposed rule 
published by CDC in 1995, or repropose other procedures and criteria 
for this process. FDA is inviting laboratory groups, medical 
professional societies, patient groups, manufacturers, manufacturing 
associations, and other interested parties to attend this open public 
workshop regarding the criteria for waiver. To the extent possible, 
oral and written testimony should address the following general and 
specific questions:

B. General Questions for Public Input

    Criteria for waived tests under the Public Health Service Act were 
amended by FDAMA to read: Waived tests ``are laboratory examinations 
and procedures that have been approved by Food and Drug Administration 
for home use or that, as determined by the Secretary, are simple 
laboratory examinations and procedures that have an insignificant risk 
of an erroneous result, including those that (A) employ methodologies 
that are so simple and accurate to render the likelihood of erroneous 
results by the user negligible, or (B) the Secretary has determined 
pose no unreasonable risk of harm to the patient if performed 
incorrectly * * *.''
    1. What criteria should be used to demonstrate that a waived test 
is a simple laboratory examination and procedure with ``an 
insignificant risk of an erroneous result?'' For example:
    a. Should a waived test, when performed by untrained users, provide 
an accurate result with no significant clinical or statistical error 
when compared to a measure of truth? This requires availability of 
well-characterized reference methods and/or materials as part of the 
waived test assessment. The current threshold for waiver as established 
by CDC is no significant inaccuracy and no significant imprecision.
    b. Should a waived test, when performed by untrained users, provide 
a test result that shows no user error when compared to the same test 
performed in a CLIA certified lab by a trained user? This requires 
comparison of the test in a lay-user setting with performance of the 
test in a CLIA certified lab by a trained user. The threshold for 
waiver would be no difference in performance in the two settings.
    c. Should FDA apply a different model to determine the waived 
status of a test?
    2. What criteria should FDA use to determine if a methodology is 
``so simple and accurate to render the likelihood of erroneous results 
by the user negligible?''
    a. Should a waived test be so accurate when performed by untrained 
users that inaccurate results will not occur?
    b. Should a waived test have variable accuracy if used 
adjunctively? Is it acceptable to waive tests that have inaccurate 
results but do not have any major negative clinical impact? How should 
FDA make this assessment?
    3. What criteria should FDA use in determining that a test will 
``pose no unreasonable risk of harm to the patient if performed 
incorrectly?''
    4. Should the waiver process be different for screening tests that 
require a second test for confirmation? Because there are no CLIA 
standards for performance of waived testing, except instructions to 
follow the manufacturer's package insert, what is the assurance that 
confirmatory testing will be performed? Should the need for 
confirmatory testing raise, lower, or have no impact on the threshold 
for a waiver decision?

C. Specific Questions for Public Input

    5. Should accuracy be determined using comparison of the waiver 
test to a well-characterized reference method and/or materials, to a 
designated comparative method and/or materials, to a working laboratory 
method and/or materials, to a clinical algorithm for diagnosis, and/or 
to other endpoints?
    6. How many samples, what types of samples (real or artificial), by 
how many users and how many sites are appropriate to evaluate accuracy? 
(Current guidelines being followed by FDA are for performance to be 
demonstrated by laboratory users at a minimum of one site.)
    7. What should be the background of these users?
    8. What performance criteria (statistical or clinical) should FDA 
apply to the accuracy threshold for a waived test (e.g., t- test or 
McNemar test at key decision points, description of performance with 
confidence intervals at key decision points, use of set performance 
standards using a receiver operator curve-80 percent, 90 percent, 95 
percent, or other-at key decision points, and/or others)?
    9. How should FDA define precision for purposes of waiver 
determination? What types of samples, how many and what types of 
operators/sites are appropriate? Current CDC recommendation is for 20 
samples at three levels representing appropriate decision points to be 
tested at three sites by lay users using materials in either artificial 
and/or real matrices depending on availability and biohazard issues.
    10. What performance thresholds should FDA use to determine whether 
the precision studies are appropriate for waiver status (e.g., ANOVA 
(analysis of variance) analysis, use of a predefined performance goal, 
such as Tonks' formula, or percent agreement out of total repeat runs)?
    11. What interference studies are appropriate to establish 
performance of waived tests (e.g., effects of hemolysis, lipemia, 
etc.)?
    12. What environmental studies or flex (stress) studies are 
appropriate to establish performance of waived tests (e.g., temperature 
or humidity stresses, short fills)?
    13. What additional studies (if any) should be submitted for 
evaluation of qualitative tests for waiver?
    14. What additional studies (if any) should be submitted for 
evaluation of quantitative tests for waiver?
    This will be an informal meeting conducted in accordance with 21 
CFR 10.65.

    Dated: July 14, 2000.
Lillian J. Gill,
Acting Deputy Director for Science, Center for Devices and Radiological 
Health.
[FR Doc. 00-18456 Filed 7-20-00; 8:45 am]
BILLING CODE 4160-01-F