Document ID: FDA-2011-D-0357-0001
Agency: fda
Document Type: Notice
Title: Food and Drug Administration Notification and Medical Device Reporting for Laboratory Developed Tests; Draft Guidance for Industry,
Food and Drug Administration Staff, and Clinical Laboratories; Availability
Posted Date: 2014-10-03T04:00Z

[Federal Register Volume 79, Number 192 (Friday, October 3, 2014)]
[Notices]
[Pages 59779-59782]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2014-23586]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2011-D-0357]

Food and Drug Administration Notification and Medical Device 
Reporting for Laboratory Developed Tests; Draft Guidance for Industry, 
Food and Drug Administration Staff, and Clinical Laboratories; 
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availability of the draft guidance entitled ``FDA Notification and 
Medical Device Reporting for Laboratory Developed Tests (LDTs).'' This 
draft guidance document is intended to describe the process for 
clinical laboratories to notify FDA of the laboratory developed tests 
(LDTs) they manufacture as well as to describe the Medical Device 
Reporting (MDR) requirements for clinical laboratories manufacturing 
LDTs. LDTs are those in vitro diagnostic devices that are intended for 
clinical use and designed, manufactured, and used within a single 
laboratory. This draft guidance is not final nor is it in effect at 
this time.

DATES: Although you can comment on any guidance at any time (see 21 CFR 
10.115(g)(5)), to ensure that the Agency considers your comment on this 
draft guidance before it begins work on the final version of the 
guidance, submit either electronic or written comments on the draft 
guidance by February 2, 2015.

ADDRESSES: An electronic copy of the guidance document is available for 
download from the Internet. See the SUPPLEMENTARY INFORMATION section 
for information on electronic access to the guidance. Submit written 
requests for single hard copies of the draft guidance document entitled 
``FDA Notification and Medical Device Reporting for Laboratory 
Developed Tests (LDTs)'' to the Office of the Center Director, Guidance 
and Policy Development, Center for Devices and Radiological Health 
(CDRH), Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 
66, Rm. 5431, Silver Spring, MD 20993-0002; or to the Office of 
Communication, Outreach and Development (HFM-40), Center for Biologics 
Evaluation and Research (CBER), Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, MD 20993-0002. Send 
one self-addressed adhesive label to assist that office in processing 
your request. The guidance may also be obtained by mail by calling CBER 
at 1-800-835-4709 or 240-402-7800.
    Submit electronic comments on the draft guidance to http://www.regulations.gov. Submit written comments to the Division of Dockets 
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852. Identify comments with the docket number 
found in brackets in the heading of this document.

FOR FURTHER INFORMATION CONTACT: LDTframework@fda.hhs.gov; or Katherine 
Serrano, Center for Devices and Radiological Health, Food and Drug 
Administration, 10903 New Hampshire Ave., Bldg. 66, Rm. 5646, Silver 
Spring, MD 20993-0002, 240-402-4217; or Stephen Ripley, Center for 
Biologics Evaluation and Research, Food and Drug Administration, 10903 
New Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993-0002, 
240-402-7911.

SUPPLEMENTARY INFORMATION:

I. Background

    In 1976, Congress enacted the Medical Device Amendments (MDA) 
(Public Law 94-295), which amended the

[[Page 59780]]

Federal Food, Drug, and Cosmetic Act (the FD&C Act) to create a 
comprehensive system for the regulation of medical devices intended for 
use in humans. At that time, the definition of a device was amended to 
make explicit that it encompasses in vitro diagnostic devices (IVDs): 
``The term `device' . . . means an instrument, apparatus, implement, 
machine, contrivance, implant, in vitro reagent, or other similar or 
related article. . . .'' (section 201(h) of the FD&C Act (21 U.S.C. 
321(h)). The definition of device applies equally to IVDs manufactured 
by conventional device manufacturers and those manufactured by 
laboratories. An IVD, therefore, meets the device definition 
irrespective of where and by whom it is manufactured.
    However, since the implementation of the MDA of 1976, FDA has 
generally exercised enforcement discretion so that the Agency has 
generally not enforced applicable provisions under the FD&C Act and FDA 
regulations with respect to LDTs, a subset of IVDs that are intended 
for clinical use and designed, manufactured, and used within a single 
laboratory. Given a changing landscape in terms of the volume, 
technology, and business model of IVDs offered as LDTs since 1976, in 
combination with the increasingly important role of diagnostic devices, 
including LDTs, in critical clinical treatment decisions, the FDA does 
not believe that generally exercising enforcement discretion with 
respect to the regulatory requirements for these devices remains 
appropriate.
    Consistent with the draft guidance entitled ``Framework for 
Regulatory Oversight of Laboratory Developed Tests (LDTs)'' that is 
being distributed for comment contemporaneously with this document, FDA 
intends to enforce certain medical device regulatory requirements for 
LDTs and device-manufacturer requirements for laboratories that 
manufacture, prepare, propagate, compound, assemble, or process LDTs. 
FDA intends to collect information regarding LDTs currently being used 
by laboratories through a notification process. In addition, FDA 
intends to enforce the requirements under part 803 (21 CFR part 803) 
for reporting safety issues related to LDTs, to provide a mechanism for 
collecting information on any known or suspected adverse events related 
to the use of an LDT. FDA believes that this is the appropriate 
regulatory oversight approach to adopt initially in achieving the 
desired public health goal of assuring that these IVDs used in the 
provision of health care, regardless of the manufacturer, provide 
reasonable assurance of safety and effectiveness.
    FDA welcomes comments on all aspects of this guidance, as well as 
on the following specific issue: FDA notes that some laboratory 
networks (i.e., more than one laboratory under the control of the same 
parent entity) offer the same test in multiple laboratories throughout 
their network. Although devices in this scenario do not meet FDA's 
definition of an LDT (i.e., they are not designed, manufactured and 
used within a single laboratory), FDA would like feedback on whether a 
single notification from the laboratory network for that test is 
sufficient, provided that the laboratory network indicates in the 
notification to FDA that the test is offered at multiple sites. 
Elsewhere in this issue of the Federal Register, FDA is issuing a 
notice announcing the availability of the draft guidance entitled 
``Framework for Regulatory Oversight of Laboratory Developed Tests 
(LDTs)'' that also identifies specific issues for comment.
    Additionally, FDA intends to hold a public webinar in late October 
2014 to summarize the proposed oversight framework and answer 
clarification questions from stakeholders. The webinar will not require 
registration and will be announced at least 1 week in advance on FDA's 
Web site. It will be recorded and made available on FDA's Web site 
shortly thereafter.

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 FDA 
notification and medical device reporting requirements for LDTs. 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

    Persons interested in obtaining a copy of the draft guidance may do 
so by downloading an electronic copy from the Internet. A search 
capability for all CDRH guidance documents is available at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/default.htm. Guidance documents are also available at 
http://www.regulations.gov or on the CBER Internet at http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/default.htm.
    Persons unable to download an electronic copy of ``FDA Notification 
and Medical Device Reporting for Laboratory Developed Tests (LDTs)'' 
may send an email request to CDRH-Guidance@fda.hhs.gov to receive an 
electronic copy of the document. Please use the document number 1738 to 
identify the guidance you are requesting.

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: Notification for Laboratory Developed Tests (LDTs).
    FDA intends to collect information from laboratories regarding 
their current LDTs and new LDTs through a notification process. This 
information collection is needed to classify LDTs and to prioritize 
enforcement of premarket review requirements for categories of LDTs 
based on risk using a public process. Specifically, FDA plans to use 
advisory panels to provide recommendations to the Agency on LDT risks, 
classification and prioritization of enforcement of applicable 
regulatory requirements on certain categories of LDTs, as appropriate. 
Additionally, the notification information will be made

[[Page 59781]]

available in part to the laboratory community and interested 
stakeholders to act as a resource for accessing information on the LDTs 
currently being used by laboratories. If these data are not collected, 
FDA and interested stakeholders will not have reliable data on the 
types of LDTs currently used. Further, because notification data will 
be used to classify LDTs and prioritize enforcement of premarket review 
requirements based on risk, it will benefit laboratories to provide the 
most accurate information possible to ensure that appropriate 
classification is made.
    To facilitate future FDA regulatory activity for LDTs, clinical 
laboratories should notify FDA of all of the LDTs manufactured, 
prepared, propagated, compounded, assembled, or processed by their 
laboratories. To appropriately notify FDA of all LDTs manufactured at 
an establishment, the owner/operator should provide information on the 
data elements identified in the following paragraph for each LDT 
manufactured at their establishment. Laboratory owner/operators with 
LDTs currently being used in their laboratories should begin to report 
this information no later than 6 months after publication, in final 
form, of the ``Framework for Regulatory Oversight of Laboratory 
Developed Tests (LDTs)'' guidance document referred to in section I. 
Background. Starting 6 months after publication of the final version of 
the ``Framework for Regulatory Oversight of Laboratory Developed Tests 
(LDTs)'' guidance, laboratories that intend to offer new LDTs should 
provide notification prior to offering the LDT for clinical use. It 
should be noted that when laboratories make a significant change to the 
marketed intended use of an LDT for which they have previously provided 
notification, the LDT will be considered by the FDA to be a new LDT 
and, therefore, a new notification should be provided prior to offering 
that LDT for clinical use.

Data Elements to be Reported \1\

     Laboratory Name
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    \1\ Please refer to Appendix A of the draft guidance document 
for a more detailed discussion of data elements.
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     Laboratory Contact Email Address
     Test Name
     Monthly Test Volume
     Intended Use
     Clinical Use of Test
     What is measured or detected (i.e. analyte, measurand, 
etc.)
     Disease/Condition for which the diagnostic device is 
indicated
     Patient Population
     Does the patient population include pediatric patients? 
(<21 years old)
     Sample Type
     Test Method
     Is the test a modification of an FDA cleared/approved 
test?
     If the test is a modification of an FDA cleared/approved 
test, what modifications were made?
    Respondents to this collection of information are manufacturers of 
LDTs. FDA estimates the burden of this collection as follows.

                            Table 1--Estimated Annual Reporting Burden First Year\1\
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                                                    Number of                     Average burden
            Activity                Number of     responses per   Total annual     per response     Total hours
                                   respondents     respondent       responses       (in hours)
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LDT Notification--Initial                   650               1             650              1               650
 notification..................
LDT Notification--Subsequent                650              16          10,400              0.5           5,200
 first year notifications......
                                --------------------------------------------------------------------------------
    Total......................  ..............  ..............  ..............  ...............           5,850
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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 Reporting Burden Subsequent Years \1\
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                                                    Number of                     Average burden
            Activity                Number of     responses per   Total annual     per response     Total hours
                                   respondents     respondent       responses       (in hours)
----------------------------------------------------------------------------------------------------------------
LDT Notification--Subsequent                650               1             650              0.5             325
 years.........................
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

    Upon publication of a final guidance based on this draft guidance, 
FDA expects approximately 650 manufacturers to provide notification 
information regarding approximately 17 LDTs each. The number of 
respondents and total number of responses are based on information 
provided by New York State. Specifically, in July 2014, New York State 
indicated that it has reviewed 9,800 submissions from 565 labs. While 
these numbers represent the best estimates available for the number of 
LDTs currently on the market, FDA acknowledges that additional LDTs may 
be offered to patients in the United States that are not currently 
offered in New York State, and therefore, have not undergone review. To 
take into account the possibility that the number of LDTs and number of 
labs in New York State understate the totals for the United States, FDA 
assumes that the nationwide totals are 10 percent higher and, 
therefore, estimates that there are approximately 11,000 LDTs 
manufactured in 650 labs. To corroborate our estimate of the total 
number of responses, i.e., the total number of LDTs currently being 
offered, we looked at National Institutes of Health Genetic Test 
Registry data. In June 2014, the registry included approximately 7,600 
genetic tests that are not FDA-approved or cleared, but are currently 
offered. If we assume that genetic tests represent roughly 70 to 80 
percent of all LDTs, this supports our estimate of 11,050 LDTs (total 
annual responses in the first year).
    FDA estimates an average of 17 LDTs offered per laboratory based 
upon the ratio of labs offering LDTs to the number of LDT submissions 
received by New York State. We therefore estimate that there will be 
650 respondents (manufacturers of LDTs) and 17 responses per respondent 
(LDT notifications) in the first year. This results in 11,050 total 
annual responses in the first year.

[[Page 59782]]

    FDA acknowledges that according to the CLIA (Clinical Laboratory 
Improvement Amendments) program at CMS (August 2014), there are 
approximately 11,000 CLIA-certified high complexity labs that have the 
appropriate certifications to manufacture LDTs. However, FDA is not 
aware of information describing the exact number of certified high 
complexity laboratories currently offering LDTs. Therefore, FDA has 
relied upon the information provided by New York State when creating 
these estimates. FDA acknowledges that, without firm data on the number 
of labs offering LDTs or the number of tests offered per lab, the 
estimate of the number of respondents is necessarily uncertain.
    After the initial notification, respondents will only notify FDA of 
new tests or modifications that affect performance or intended use. We 
estimate the number of tests in subsequent years to be approximately 5 
percent of the estimated number of initial notifications.
    FDA bases its estimate of the average burden per response on Agency 
creation of a mock notification. We would expect labs to take up to an 
hour for their first notification and only 30 minutes for subsequent 
notifications, due to familiarity with the system.
    Therefore, we estimate the total reporting burden to respondents to 
be 5,850 hours for the first year and 325 hours for subsequent years.
    This draft guidance also refers to previously approved collections 
of information found in FDA regulations. These collections of 
information 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 collections of information in 21 CFR part 803 (medical 
device reporting) have been approved under OMB control numbers 0910-
0291 and 0910-0437; the collections of information in 21 CFR part 806 
(reports of corrections and removals) have been approved under OMB 
control number 0910-0359; and the collections of information in 21 CFR 
part 807, subparts B and C (registration and listing) have been 
approved under OMB control number 0910-0625.

V. Comments

    Interested persons may submit either electronic comments regarding 
this document to http://www.regulations.gov or written comments to the 
Division of Dockets Management (see ADDRESSES). It is only necessary to 
send one set of comments. Identify comments 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, and will be posted to the docket at http://www.regulations.gov.
    Comments will also be accepted at a public meeting, which will be 
held prior to finalizing this draft guidance. A 2-day meeting is 
tentatively scheduled for early January 2015 and will be announced 
separately in the Federal Register.

    Dated: September 29, 2014.
Peter Lurie,
Associate Commissioner for Policy and Planning.
[FR Doc. 2014-23586 Filed 9-30-14; 11:15 am]
BILLING CODE 4164-01-P