Administrative Procedures for CLIA Categorization Guidance

Administrative Procedures
for CLIA Categorization
_______________
Guidance for Industry and Food
and Drug Administration
Staff
Document issued on March 12, 2014
This document supersedes the guidance by the same title issued
May 7, 2008.
OMB control number: 0910-0607
Expiration Date: 10/31/2016
See additional PRA statement in Section 4 of this guidance.

For questions about this document, contact Ann Chappie at 301-796-6139 or by e-mail
at ann.chappie@fda.hhs.gov, or contact the Office of In Vitro Diagnostics and
Radiological Health, 301-796-5711.

U.S. Department of Health and Human Services
Food and Drug Administration
Center for Devices and Radiological
Health
Office of In Vitro Diagnostics and Radiological
Health

Contains Nonbinding Recommendations

Preface
Public Comment
You may submit electronic comments and suggestions at any time for Agency consideration
to http://www.regulations.gov. Submit written comments to the Division of Dockets
Management, Food and Drug Administration, 5630 Fishers Lane, Room 1061, (HFA-305),
Rockville, MD, 20852.
Identify all comments with Docket No FDA-2008-D-0228. Comments may not be acted
upon by the Agency until the document is next revised or updated.

Additional Copies
Additional copies are available from the Internet. You may also send an e-mail request
to CDRH-Guidance@fda.hhs.gov to receive a copy of the guidance. Please use the
document number 1143 to identify the guidance you are requesting.

Contains Nonbinding Recommendations

Table of Contents

1. Introduction ......................................................................................................................... 4
2. Procedures for Determination of CLIA Categorization ...................................................... 5
3. CLIA Waiver Protocols and Applications ........................................................................... 7
4. Paperwork Reduction Act of 1995 ...................................................................................... 8

3

Contains Nonbinding Recommendations

Administrative Procedures for CLIA
Categorization
____________________________________

Guidance for Industry and
Food and Drug Administration Staff
This guidance represents the Food and Drug Administration's (FDA's) current thinking on
this topic. It does not create or confer any rights for or on any person and does not operate
to bind FDA or the public. You can use an alternative approach if the approach satisfies the
requirements of the applicable statutes and regulations. If you want to discuss an alternative
approach, contact the FDA staff responsible for implementing this guidance. If you cannot
identify the appropriate FDA staff, call the appropriate number listed on the title page of this
guidance.

1. Introduction
On February 28, 1992, the Department of Health and Human Services (DHHS) published
laboratory standards regulations (57 FR 7002) implementing the Clinical Laboratory
Improvement Amendments of 1988 (CLIA) (42 U.S.C. 263a). The implementing regulations are
codified at 42 CFR Part 493. CLIA regulates laboratory testing and requires that clinical
laboratories obtain a certificate before accepting materials derived from the human body for the
purpose of providing information for the diagnosis, prevention, or treatment of any disease or the
impairment of, or assessment of the health of human beings. The type of CLIA certificate a
laboratory obtains depends upon the complexity of the tests it performs. CLIA regulations
describe the following three levels of test complexity: waived tests, moderate complexity tests,
and high complexity tests. 42 CFR 493.5(a).
On January 31, 2000, the responsibility for categorization of commercially available in vitro
diagnostic (IVD) tests was transferred from the Centers for Disease Control and Prevention
(CDC) to the Food and Drug Administration (FDA) Center for Devices and Radiological Health
(CDRH). 1 This allows IVD manufacturers to submit premarket notifications or applications for
tests and requests for complexity categorization of these tests under CLIA to one agency. Per the
December 30, 1999, Notice of the Federal Register, FDA/CDRH’s responsibility for CLIA
complexity categorization explicitly applies to clinical laboratory devices:
1

64 FR 73561, December 30, 1999. See also the delegation to FDA to categorize commercially
available in vitro diagnostic tests and perform associated functions (69 FR 22849, April 27,
2004).
4

Contains Nonbinding Recommendations

•
•
•
•

under premarket review by CDRH,
under premarket review by other FDA Centers,
exempt from premarket notification, and
that are legally marketed and for which the sponsor is seeking a waiver
categorization.

FDA/CDRH’s general administrative procedures vary for each of the categories above and are
described within this document. This guidance does not specifically address the recommended
content of CLIA waiver applications. For more information on what should be included in CLIA
waiver applications, you may refer to the guidance entitled, “Guidance for Industry and FDA
Staff: Recommendations for Clinical Laboratory Improvement Amendments of 1988 (CLIA)
Waiver Applications for Manufacturers of In Vitro Diagnostic Devices”
(http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm0
79632.htm).
This guidance is updated to include information regarding FDA’s internal administrative
processes, including CDRH’s e-copy program which is voluntary for CLIA categorizations.
FDA's guidance documents, including this guidance, do not establish legally enforceable
responsibilities. Instead, guidances describe the Agency's current thinking on a topic and should
be viewed only as recommendations, unless specific regulatory or statutory requirements are
cited. The use of the word should in Agency guidances means that something is suggested or
recommended, but not required.

2. Procedures for Determination of CLIA Categorization
a. Categorization of Clinical Laboratory Devices Under Premarket Review
CLIA categorization of IVD tests is determined by FDA at the time of review of a premarket
notification submission (510(k)) or a premarket approval application (PMA) under the Federal
Food, Drug, and Cosmetic Act. Upon receipt of a marketing application in CDRH, FDA will
automatically create a second discrete submission tracking number for the CLIA process and
notify the sponsor of their CLIA Record (“CR”) number in addition to their premarket
submission 510(k) (“K”) or PMA (“P”) number. In cases where the premarket submission is
reviewed by another FDA Center (e.g., CBER), the other Center will notify CDRH at the time of
clearance/approval of the IVD test. At that time, FDA will automatically create a discrete CLIA
Record (“CR”) number to track CDRH’s categorization of the test and notify the sponsor of their
CLIA Record number.
FDA determines test complexity by reviewing the package insert test instructions in the
premarket submission, using the criteria listed in 42 CFR 493.17. The tests that are not waived
by regulation under 42 CFR 493.15 and are not cleared or approved for home use or for over-thecounter use, may be categorized either as moderate or high complexity.
FDA will attempt to notify sponsors of the complexity categorization within two weeks of a
5

Contains Nonbinding Recommendations
positive marketing decision (e.g., a substantial equivalence determination for a 510(k) or an
approval decision for a PMA). Categorization is effective as of the date of the written
notification to the manufacturer (see 42 CFR 493.17(c)(1)(ii)).
A searchable database of CLIA categorizations for IVD devices is available at
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCLIA/clia.cfm. FDA periodically posts all
categorizations in the public CLIA database with reference to the premarket submission number.
b. Request for Categorization of Legally Marketed Devices
In cases where a 510(k) or PMA is not needed but CLIA categorization is still appropriate (e.g.,
devices exempt from premarket notification), manufacturers should submit a request for CLIA
categorization, including a copy of the test package insert with test instructions, to the CDRH
Document Control Center at the following address:
Food and Drug Administration
Center for Devices and Radiological Health
Document Mail Center - WO66-G609
10903 New Hampshire Avenue
Silver Spring, Maryland 20993-0002
To expedite review, FDA strongly encourages submission of an eCopy. See “eCopy Program for
Medical Device Submissions.”
(http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocu
ments/UCM313794.pdf
FDA will assign a discrete CLIA Record (“CR”) number to this submission, notify the sponsor
of the tracking number, and attempt to notify sponsors of the categorization within 30 days of the
request. FDA will post the categorization in the public CLIA database with reference to the
CLIA Record (“CR”) number.
Additionally, FDA recommends that where the name of an approved or cleared device changes,
or the name of the manufacturer or distributor changes, the manufacturer should submit the
updated label and request for CLIA categorization to the CDRH Document Control Center at the
address listed above so that its record of categorized tests in the public database is accurate.
When requesting CLIA categorizations for a name change for multiple IVD tests (e.g.,
manufacturer or distributor device name change), FDA recommends that this information be
presented using a spreadsheet (e.g., Excel). Sponsors may download the information for their
current categorized tests from the CLIA database using the “export to Excel” function, add a new
column to the spreadsheet after the current test system name, and enter the new test system name
in this column. The spreadsheet could be provided to CDRH as part of the eCopy. The
application should reference one cleared marketing application in the cover letter to expedite
processing of the new categorization letters. Upon receipt of a request for categorization due to a
manufacturer or distributor name change, FDA will assign a discrete CLIA Record (“CR”)
number to this submission, notify the sponsor of the tracking number, and attempt to notify
sponsors of the categorization within 30 days of the request. FDA will post the categorization in
the public CLIA database with reference to the CLIA Record (“CR”) number.
6

Contains Nonbinding Recommendations

3. CLIA Waiver Protocols and Applications
A test initially categorized as moderately complex might meet the statutory criteria for CLIA
waiver if the device is simple to use and the sponsor demonstrates in studies conducted at the
intended use sites that the test is accurate and poses an insignificant risk of erroneous results. If a
Sponsor of a test categorized as moderate complexity believes their test meets the statutory
criteria for CLIA waiver, they may submit a CLIA Waiver by Application to request
categorization of the test system as waived. Such a submission should be mailed to the CDRH
Document Control Center (DCC) at the address listed above and identified as a CLIA Waiver by
Application submission. To expedite review, FDA strongly encourages submission of a
validated eCopy per the Guidance Document “eCopy Program for Medical Device Submissions.”
(http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocu
ments/UCM313794.pdf )
All CLIA Waivers by Application should reference either a cleared/approved marketing
application (e.g., 510(k), PMA, BLA) or a Pre-Submission during which agreement was reached
on a Dual 510(k) and CLIA Waiver by Application strategy. CLIA Waivers by Application are
not accepted for devices that are under premarket review at the time of submission. A Dual
510(k) and CLIA Waiver by Application should contain the complete 510(k) and waiver
application in a single submission and is subject to 510(k) Refuse to Accept (RTA) policies
outlined in the Guidance Document “Refuse to Accept Policy for 510(k)s.”
(http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocu
ments/UCM315014.pdf). FDA/CDRH will assign a discrete CLIA Waiver by Application
(“CW”) tracking number and notify the sponsor of the tracking number associated with their
submission.
Performance goals for CLIA Waiver by Applications filed from FY 2013 through FY 2017
(MDUFA III) are defined as follows in the MDUFA III Commitment Letter.
Action

Review Time
(FDA days)

Performance Level
FY2013 – FY2017

90

95%

No Panel

180

95%

With Panel

330

95%

Dual (510(k) and CLIA
Waiver by Application) [1]

210

90%

Substantive Interaction
MDUFA Decision

[1]

Note that this performance goal applies to both the CLIA Waiver by Application and
the 510(k) marketing submission.
7

Contains Nonbinding Recommendations
A Substantive Interaction may be a request for Additional Information (via letter or email), a
notification that review will Proceed Interactively (via email), or a notification of Waiver
Granted (via formal letter). A MDUFA Decision may be a notification of Waiver Granted (via
formal letter), notification of Wavier Denial (via formal letter), or withdrawal by the sponsor.
The goals for Substantive Interaction and MDUFA Decisions are in terms of FDA Days, which
are defined in the MDUFA III Commitment Letter as those calendar days when a submission is
considered to be under review at the Agency for submissions that have been accepted. FDA
Days begin on the date of receipt of the submission.
Upon notification of a Waiver Granted, FDA will post the waiver categorization in the public
CLIA database with reference to the premarket submission number per current practice.
For additional information regarding data to support a CLIA Waiver by Application, refer to the
guidance entitled, “Guidance for Industry and FDA Staff: Recommendations for Clinical
Laboratory Improvement Amendments of 1988 (CLIA) Waiver Applications for Manufacturers
of In Vitro Diagnostic Devices”
(http://www.fda.gov/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm079
632.htm).
Manufacturers have the option to submit their planned protocols or study designs to support
CLIA waiver in order to obtain feedback from FDA prior to conducting the study. These
planned protocols or study designs should be submitted to the CDRH Document Control Center
(DCC) at the address listed above and identified as a Pre-Submission. For additional
information on the Pre-Submission process, please refer to the Guidance “Requests for
Feedback on Medical Device Submissions: The Pre-Submission Program and Meetings with
Food and Drug Administration Staff”
(http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocu
ments/UCM311176.pdf). Pre-Submissions for CLIA Waiver by Applications should include a
reference to the original 510(k) or PMA number, the protocol/study design, and a valid eCopy.

4. Paperwork Reduction Act of 1995
This guidance contains information collection provisions that are subject to review by the
Office of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (44
U.S.C. 3501-3520).
The time required to complete this information collection is estimated to average one hour per
response, including the time to review instructions, search existing data sources, gather the
data needed, and complete and review the information collection. Send comments regarding
this burden estimate or suggestions for reducing this burden to:
Department of Health and Human Services
Food and Drug Administration
Office of Chief Information Officer
Paperwork Reduction Act (PRA) Staff
PRAStaff@fda.hhs.gov
8

Contains Nonbinding Recommendations
This guidance also refers to previously approved collections of information found in FDA
regulations. The collections of information in 21 CFR Part 801 have been approved under
OMB control number 0910-0485; the collections of information in 21 CFR Part 807, subpart
E have been approved under OMB control number 0910-0120; and the collections of
information for CLIA waiver by application have been approved under OMB control number
0910-0598.
An agency may not conduct or sponsor, and a person is not required to respond to, a collection
of information unless it displays a currently valid OMB control number. The OMB control
number for this information collection is 0910-0607 (expires 10/31/2016).

9