[Federal Register Volume 70, Number 172 (Wednesday, September 7, 2005)]
[Notices]
[Pages 53231-53233]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-17732]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2001D-0044]


Draft Guidance for Industry and Food and Drug Administration 
Staff: Recommendations for Clinical Laboratory Improvement Amendments 
of 1988 Waiver Applications; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of the draft guidance entitled ``Recommendations for 
Clinical Laboratory Improvement Amendments of 1988 (CLIA) Waiver 
Applications.'' FDA is issuing this draft guidance to recommend an 
approach for determining whether a laboratory test may be performed by 
laboratories with a certificate of waiver under CLIA. This draft 
guidance replaces the previous draft guidance entitled ``Guidance for 
Clinical Laboratory Improvement Amendments of 1988 (CLIA) Criteria for 
Waiver,'' March 1, 2001.

DATES: Submit written or electronic comments on this draft guidance by 
December 6, 2005. Submit written comments on the information collection 
provisions by November 7, 2005.

ADDRESSES: Submit written requests for single copies on a 3.5'' 
diskette of the draft guidance document entitled ``Recommendations for 
Clinical Laboratory Improvement Amendments of 1988 (CLIA) for Waiver 
Applications'' to the Division of Small Manufacturers, International, 
and Consumer Assistance (HFZ-220), Center for Devices and Radiological 
Health, Food and Drug Administration, 1350 Piccard Dr., Rockville, MD 
20850. Send one self-addressed adhesive label to assist that office in 
processing your request, or fax your request to 301-443-8818. See the 
SUPPLEMENTARY INFORMATION section for information on electronic access 
to the guidance.
    Submit written comments concerning this draft guidance and the 
information collection provisions to the Division of Dockets Management 
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852. Submit electronic comments to http://www.fda.gov/dockets/ecomments. Identify comments with the docket number found in 
brackets in the heading of this document.

FOR FURTHER INFORMATION CONTACT: Carol Benson, Center for Devices and 
Radiological Health (HFZ-440), Food and Drug Administration, 9200 
Corporate Blvd., Rockville, MD 20850, 240-276-0443, ext. 144.

SUPPLEMENTARY INFORMATION:

I. Background

    CLIA requires that clinical laboratories obtain a certificate from 
the Secretary of Health and Human Services (the Secretary) before 
accepting materials derived from the human body for laboratory tests 
(42 U.S.C. 263(b)).
    Laboratories that perform only tests that are ``simple'' and that 
have an ``insignificant risk of an erroneous result'' may obtain a 
certificate of waiver (42 U.S.C. 263a(c)(2)). The Secretary has 
delegated to FDA the authority to determine under CLIA whether 
particular tests (waived tests) are ``simple'' and have ``an 
insignificant risk of an erroneous result'' (April 27, 2004, 69 FR 
22849). This draft guidance document describes recommendations for 
device manufacturers submitting to FDA an application for determination 
that a cleared or approved device meets this CLIA standard (CLIA waiver 
application).
    FDA previously issued a draft guidance entitled ``Clinical 
Laboratory Improvement Amendments of 1988 (CLIA) Criteria for Waiver'' 
on March 1, 2001. This new draft guidance replaces the previous draft 
guidance.
    The changes compared to the previous draft guidance include the 
following: (1) Greater emphasis on scientifically-based flex studies 
and validation studies, linked to the hazard analysis for each device; 
(2) recognition that reference methods may not be

[[Page 53232]]

available for every device type (although devices should be traceable 
to methods of known accuracy when true reference methods are 
available); (3) additional emphasis on use of quality control 
procedures; (4) greater emphasis on intended users during studies 
testing the device; and (5) updated study recommendations with emphasis 
on use of patient specimens, in an intended use environment, over time.
    FDA bases the recommendations in this draft guidance on its 
interpretation of CLIA, FDA's experience with CLIA complexity 
determinations, and the agency's interactions with stakeholders. One of 
the interactions with stakeholders was at an open public workshop on 
August 14 and 15, 2000. In addition, a proposal presented by (Advanced 
Medical Technology Association) AdvaMed at the September 2003 Clinical 
Laboratory Improvement Advisory Committee (CLIAC) meeting, and 
recommendations proposed by CLIAC during the February 2004 meeting were 
considered in the development of this guidance.

II. Significance of Guidance

    This draft guidance is being issued consistent with FDA's good 
guidance practices regulation (21 CFR 10.115). The draft guidance when 
finalized will represent the agency's current thinking on 
recommendations for CLIA Waiver Applications. It does not create or 
confer any rights for or on any person and does not operate to bind FDA 
or the public. An alternative approach may be used if such approach 
satisfies the requirements of the applicable statute and regulations.

III. Electronic Access

    To receive ``Clinical Laboratory Improvement Amendments of 1988 
(CLIA) Waiver Applications,'' you may either send a fax request to 301-
443-8818 to receive a hard copy of the document, or send an e-mail 
request to [email protected] to receive a hard copy or an electronic 
copy. Please use the document number (1171) to identify the guidance 
you are requesting.
    Persons interested in obtaining a copy of the draft guidance may 
also do so by using the Internet. CDRH maintains an entry on the 
Internet for easy access to information including text, graphics, and 
files that may be downloaded to a personal computer with Internet 
access. Updated on a regular basis, the CDRH home page includes device 
safety alerts, Federal Register reprints, information on premarket 
submissions (including lists of approved applications and 
manufacturers' addresses), small manufacturer's assistance, information 
on video conferencing and electronic submissions, Mammography Matters, 
and other device-oriented information. The CDRH Web site may be 
accessed at http://www.fda.gov/cdrh. A search capability for all CDRH 
guidance documents is available at http://www.fda.gov/cdrh/guidance.html. Guidance documents are also available on the Division of 
Dockets Management Internet site at http://www.fda.gov/ohrms/dockets.

IV. Paperwork Reduction Act of 1995

    Under the Paperwork Reduction Act of 1995 (the PRA) (44 U.S.C. 
3501-3520), Federal agencies must obtain approval from the Office of 
Management and Budget (OMB) for each collection of information they 
conduct or sponsor. ``Collection of information'' is defined in 44 
U.S.C. 3502(3) and 5 CFR 1320.3(c) and includes agency requests or 
requirements that members of the public submit reports, keep records, 
or provide information to a third party. Section 3506(c)(2)(A) of the 
PRA (44 U.S.C. 3506(c)(2)(A)) requires Federal agencies to provide a 
60-day notice in the Federal Register concerning each proposed 
collection of information before submitting the collection to OMB for 
approval. To comply with this requirement, FDA is publishing notice of 
the proposed collection of information set forth in this document.
    With respect to the following collection of information, FDA 
invites comments on the following topics: (1) Whether the proposed 
collection of information is necessary for the proper performance of 
FDA's functions, including whether the information will have practical 
utility; (2) the accuracy of FDA's estimate of the burden of the 
proposed collection of information, including the validity of the 
methodology and assumptions used; (3) ways to enhance the quality, 
utility, and clarity of the information to be collected; and (4) ways 
to minimize the burden of the collection of information on respondents, 
including through the use of automated collection techniques, when 
appropriate, and other forms of information technology.
    Title: Recommendations for CLIA Waiver Applications
    Description: Congress passed the CLIA (Public Law 100-578) in 1988 
to establish quality standards for all laboratory testing. The purpose 
was to ensure the accuracy, reliability, and timeliness of patient test 
results regardless of where the test took place. CLIA requires that 
clinical laboratories obtain a certificate from the Secretary of Health 
and Human Services before accepting materials derived from the human 
body for laboratory tests (42 U.S.C. 263a(b)). Laboratories that 
perform only tests that are ``simple'' and that have an ``insignificant 
risk of an erroneous result'' may obtain a certificate of waiver (42 
U.S.C. 263a(c)(2)). The Secretary has delegated to FDA the authority to 
determine whether particular tests (waived tests) are ``simple'' and 
have ``an insignificant risk of an erroneous result'' under CLIA (69 FR 
22849). This guidance document describes recommendations for device 
manufacturers submitting to FDA an application for determination that a 
cleared or approved device meets this CLIA standard (CLIA waiver 
application).
    The guidance recommends that CLIA waiver applications include a 
description of the features of the device that make it ``simple''; a 
report describing a hazard analysis that identifies potential sources 
of error, including a summary of the design and results of flex studies 
and conclusions drawn from the flex studies; a description of fail-safe 
and failure alert mechanisms and a description of the studies 
validating these mechanisms; a description of clinical tests that 
demonstrate the accuracy of the test in the hands of intended 
operators; and statistical analyses of clinical study results. The 
guidance also makes recommendations concerning labeling of waived 
tests. The burden associated with most of these labeling 
recommendations is approved under OMB control number 0910-0485. Only 
new information collections not already approved are included in the 
estimate below. The recommendation for quick reference instructions is 
a new information collection which FDA is submitting to OMB for review. 
Quick reference instructions are a short version of the instructions 
that are written in simple language and that can be posted. The 
guidance also notes that waived tests remain subject to applicable 
reporting and recordkeeping requirements under 21 CFR part 803. The 
burden associated with this provision is approved under OMB control 
number 0910-0437.
    Respondents to this collection of information are manufacturers of 
in vitro diagnostic devices.
    FDA estimates the burden of this collection as follows.

[[Page 53233]]



                                                     Table 1.--Estimated Annual Reporting Burden\1\
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                              Annual Frequency per                                                                             Operating and Maintenance
     No. of Respondents             Response          Total Annual Responses      Hours per response        Total Hours                  Costs
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40                                              1                          40                    780                 31,200                      $5,500
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\1\There are no capital costs or operating and maintenance costs associated with this collection of information.


                                                   Table 2.--Estimated Annual Recordkeeping Burden\1\
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                              Annual Frequency per                                                                             Operating and Maintenance
    No. of Recordkeepers         Recordkeeping         Total Annual Records        Hours per Record         Total Hours                  Costs
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40                                              1                          40                  2,800                112,000                     $60,700
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\1\There are no capital costs or operating and maintenance costs associated with this collection of information.

    Based on previous years' experience with CLIA waiver applications, 
FDA expects 40 manufacturers to apply for one CLIA waiver per year. The 
annual reporting burden to respondents is estimated to be 31,200 hours, 
and recordkeeping burdens for respondents is estimated to be 112,000 
hours. FDA based the reporting and recordkeeping burden on an agency 
analysis of premarket submissions with clinical trials similar to the 
waived laboratory tests.
    The total operating and maintenance cost associated with the 
implementation of this draft guidance is estimated to be $66,200. The 
cost consists of specimen collection for the clinical study (estimated 
at $23,500); laboratory supplies, reference testing and study oversight 
(estimated $26,700); shipping and office supplies (estimated $6,000); 
and educational materials, including quick reference instructions 
($10,000).

V. Comments

    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES) written or electronic comments regarding this document. 
Submit a single copy of electronic comments or two paper copies of any 
mailed comments, except that individuals may submit one paper copy. 
Comments are to be identified with the docket number found in brackets 
in the heading of this document. Received comments may be seen in the 
Division of Dockets Management between 9 a.m. and 4 p.m., Monday 
through Friday.

    Dated: August 31, 2005.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 05-17732 Filed 9-1-05; 4:00 pm]
BILLING CODE 4160-01-S