[Federal Register Volume 79, Number 226 (Monday, November 24, 2014)]
[Notices]
[Pages 69860-69863]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2014-27713]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket Nos. FDA-2011-D-0360 and FDA-2011-D-0357]
Framework for Regulatory Oversight of Laboratory Developed Tests;
Public Workshop; Request for Comments
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice of public workshop; request for comments.
-----------------------------------------------------------------------
The Food and Drug Administration (FDA) is announcing the following
public workshop entitled ``Framework for Regulatory Oversight of
Laboratory Developed Tests (LDTs).'' The purpose of this workshop is to
discuss FDA's proposal for a risk-based framework for addressing the
regulatory oversight of a subset of in vitro diagnostic devices (IVDs)
referred to as laboratory developed tests (LDTs), which are intended
for clinical use and designed, manufactured and used within a single
laboratory, and provide an additional opportunity for public comment
Dates and Times: The 2-day public workshop will be held on January
8, 2015, from 8:30 a.m. to 5:30 p.m. and on January 9, 2015 from 8:30
a.m. to 5:30 p.m.
Location: The public workshop will be held at the Natcher Center at
the National Institutes of Health Campus, 9000 Rockville Pike, Bldg.
45, Auditorium, Bethesda, MD 20814. For parking and security
information, please refer to http://www.nih.gov/about/visitor/.
Contact Person: Allen Webb, Center for Devices and Radiological
Health, Food and Drug Administration, Bldg. 66, Rm 5675, 10903 New
Hampshire Ave., Silver Spring, MD 20993, 240-402-4217,
[email protected].
Registration: Registration is free and available on a first-come,
first-served basis. Persons interested in attending this public
workshop must register online by December 12, 2014, at 4 p.m. Early
registration is recommended because facilities are limited and,
therefore, FDA may limit the number of participants from each
organization. If time and space permits, onsite registration on the day
of the public workshop will be provided beginning at 8 a.m.
If you need special accommodations due to a disability, please
contact Susan Monahan, (email: [email protected] or phone: 301-
796-5661) no later than December 19, 2014.
To register for the public workshop, please visit FDA's Medical
Devices News & Events--Workshops & Conferences calendar at http://www.fda.gov/MedicalDevices/NewsEvents/WorkshopsConferences/default.htm.
(Select this meeting/public workshop from the posted events list.)
Please provide complete contact information for each attendee,
including name, title, affiliation, email, and telephone number. If you
are unable to register online, please contact Susan Monahan (see
Registration.) Registrants will receive confirmation after they have
been accepted and will be notified if they are on a waiting list.
[[Page 69861]]
Streaming Webcast of the Public Workshop: This public workshop will
also be Webcast. Persons interested in viewing the Webcast must
register online. Early registration is recommended because Webcast
connections are limited. Organizations are requested to register all
participants, but to view using one connection per location. Webcast
participants will be sent technical system requirements and connection
access information after registration and prior to the meeting. If you
have never attended a Connect Pro event before, test your connection at
https://collaboration.fda.gov/common/help/en/support/meeting_test.htm.
To get a quick overview of the Connect Pro program, visit http://www.adobe.com/go/connectpro_overview. (FDA has verified the Web site
addresses in this document, but FDA is not responsible for any
subsequent changes to the Web sites after this document publishes in
the Federal Register.) The Webcast will be recorded and posted on FDA's
Web site after the meeting.
Requests for Oral Presentations: This public workshop includes
topic-focused public comment sessions. During online registration you
may indicate if you wish to present during a public comment session,
and which topics you wish to address. FDA has included general topics
in this document. FDA will do its best to accommodate requests to make
public comment. Individuals and organizations with common interests are
urged to consolidate or coordinate their presentations, and request
time for a joint presentation, or submit requests for designated
representatives to participate in the focused sessions. Following the
close of registration, FDA will determine the amount of time allotted
to each presenter and the approximate time each oral presentation is to
begin, and will select and notify participants by December 17, 2014.
All requests to make oral presentations must be received by the close
of registration on December 12, 2014. If selected for presentation, any
presentation materials must be emailed to Allen Webb (see Contact
Person) no later than January 6, 2015. No commercial or promotional
material will be permitted to be presented or distributed at the public
workshop.
Comments: In order to permit the widest possible opportunity to
obtain public comment, FDA is soliciting either electronic or written
comments on all aspects of the public workshop topics. The deadline for
submitting comments related to this public workshop is February 2,
2015.
Regardless of attendance at the public workshop, interested persons
may submit either electronic comments regarding this document to http://www.regulations.gov or written comments to the Division of Dockets
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852. 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. In addition, when responding to specific
questions as outlined in section II of this document, please identify
the question you are addressing. 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.
Transcripts: Please be advised that as soon as a transcript is
available, it will be accessible at http://www.regulations.gov. It may
be viewed at the Division of Dockets Management (see Comments). A
transcript will also be available in either hardcopy or on CD-ROM,
after submission of a Freedom of Information request. Written requests
are to be sent to the Division of Freedom of Information (ELEM-1029),
Food and Drug Administration, 12420 Parklawn Dr., Element Bldg.,
Rockville, MD 20857. A link to the transcripts will also be available
approximately 45 days after the public workshop on the Internet at
http://www.fda.gov/MedicalDevices/NewsEvents/WorkshopsConferences/default.htm. (Select this public workshop from the posted events list).
SUPPLEMENTARY INFORMATION:
I. Background
In 1976, Congress enacted the Medical Device Amendments (MDA),
which amended the 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 encompassed 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.
Since the implementation of the MDA of 1976, FDA has 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.
In 1976, LDTs were mostly manufactured in small volumes by local
laboratories. Many laboratories manufactured LDTs that were similar to
well-characterized, standard diagnostic devices, as well as other LDTs
that were intended for use in diagnosing rare diseases or for other
uses to meet the needs of a local patient population. LDTs at the time
tended to rely on the manual techniques used by laboratory personnel.
LDTs were typically used and interpreted directly by physicians and
pathologists working within a single institution that was responsible
for the patient. In addition, historically, LDTs were manufactured
using components that were legally marketed for clinical use (i.e.,
general purpose reagents, immunohistochemical stains, and other
components marketed in compliance with FDA regulatory requirements).
Although some laboratories today still manufacture LDTs in this
``traditional'' manner, the landscape for laboratory testing in
general, and LDTs along with it, has changed dramatically since 1976.
Today, LDTs are often used in laboratories that are independent of the
healthcare delivery entity. Additionally, LDTs are frequently
manufactured with components and instruments that are not legally
marketed for clinical use and also rely more heavily on complex, high-
tech instrumentation and software to generate results and clinical
interpretations. Moreover, technological advances have increased the
use of diagnostic devices in guiding critical clinical management
decisions for high-risk diseases and conditions, particularly in the
context of personalized medicine.
Business models for laboratories have also changed since 1976. With
the advent of overnight shipping and electronic delivery of information
(e.g., device results), a single laboratory can now easily provide
device results nationally and internationally. Today, many new LDT
manufacturers are large corporations that nationally market a limited
number of complex, high-risk devices, in contrast to 1976 when hospital
or public health laboratories used a wide range of devices that were
generally either well characterized and similar to standard devices;
used to diagnose rare diseases; or designed specifically to meet the
needs of their local patients. Together, these changes
[[Page 69862]]
have resulted in a significant shift in the types of LDTs developed,
the business model for developing them, and the potential risks they
pose to patients.
Because of changes in the complexity and use of LDTs and the
associated increased risks, as described earlier, FDA believes the
policy of general enforcement discretion towards LDTs is no longer
appropriate. To initiate this step toward greater oversight, FDA held a
2-day public meeting on July 19 and 20, 2010, to provide a forum for
stakeholders to discuss issues and concerns surrounding greater
oversight of LDTs. Comments submitted to the public docket for the July
19 and 20, 2010, public meeting were reviewed and, as appropriate,
incorporated into FDA's current proposed framework for regulatory
oversight of LDTs. FDA's July 31, 2014, Notification to Congress
concerning the Agency's intent to issue the draft guidance, ``Framework
for Regulatory Oversight of Laboratory Developed Tests (LDTs)''
(Framework draft guidance document), and the accompanying draft
guidance, ``FDA Notification and Medical Device Reporting for
Laboratory Developed Tests (LDTs),'' was made publicly available, and
these draft guidance documents were subsequently issued on October 3,
2014. See 79 FR 59776 and 79 FR 59779 (October 3, 2014). These
documents describe a risk-based framework for addressing the regulatory
oversight of LDTs, including FDA's priorities for enforcing premarket
and postmarket requirements for LDTs as well as the process by which
FDA intends to phase in enforcement of FDA regulatory requirements for
LDTs over time. As outlined in the Framework draft guidance document,
FDA proposes to continue to exercise enforcement discretion for all
applicable regulatory requirements for LDTs used solely for forensic
(law enforcement) purposes as well as certain LDTs for transplantation
when used in certified, high-complexity histocompatibility
laboratories. Additionally, FDA proposes to exercise enforcement
discretion for applicable premarket review requirements and quality
systems (QS) requirements, but enforce other applicable regulatory
requirements, including registration and listing (with the option to
provide notification instead) and adverse event reporting, for low-risk
LDTs (class I devices), LDTs for rare diseases, Traditional LDTs and
LDTs for Unmet Needs, as described in the Framework draft guidance
document. For other high- and moderate-risk LDTs, FDA proposes to
enforce applicable regulatory requirements, including registration and
listing (with the option to provide notification instead) and adverse
event reporting, and phase in enforcement of premarket and QS
requirements in a risk-based manner.
With the publication of the draft guidances, FDA announced a public
comment period soliciting feedback on all aspects of the guidance
documents as well as on the following specific issues: (1) Factors for
``Traditional LDT'' and appropriate level of enforcement discretion for
such tests; (2) factors for considering LDTs for rare diseases; (3)
manufacture and use of LDTs solely within a healthcare system as a risk
mitigation supporting some continued enforcement discretion; (4)
timeframe for phase-in enforcement of QS regulation requirements for
those LDTs called in for enforcement of premarket review requirements
early in the implementation period; and (5) the appropriateness of a
single notification for the same LDT manufactured by multiple labs
owned by a single entity.
FDA intends to use this public workshop as a forum for open
discussion with all stakeholders regarding these specific issues as
well as other considerations for how to best balance patient safety and
patient access in developing the finalized framework in a manner that
best serves public health.
II. Topics for Discussion at the Public Workshop
Issues to be considered during the sessions include:
Session 1: Components of a Test and LDT Labeling Considerations
What components do FDA cleared/approved tests and LDTs
typically include?
What labeling considerations should be taken into account
for LDTs?
How does LDT labeling affect and not affect physician
consultation with the laboratory?
Session 2: Clinical Validity/Intended Use
What is clinical validity and how is it demonstrated for
IVDs, including LDTs?
How are clinical claims or intended use related to
clinical validity?
What types of modifications may affect the intended use or
significantly affect the performance of a test?
Session 3: Categories for Continued Enforcement Discretion
As a factor for consideration of continued enforcement
discretion for premarket review and QS regulation requirements for LDTs
for rare diseases, the proposed framework for LDTs relies on the
definition of a humanitarian use device (HUD) in 21 CFR 814.102(a)(5).
Under this definition, an IVD may qualify for HUD designation when the
number of persons in the United States who may be tested with the
device is fewer than 4,000 per year. Is this an appropriate factor for
LDTs for rare diseases? If not, what factor should FDA consider for
LDTs for rare diseases?
Should enforcement discretion be limited to tests for rare
diseases that meet the definition of an LDT (a test designed,
manufactured and used within a single laboratory)?
Are the following three factors the appropriate controls
to mitigate risks due to Traditional LDTs so that continued enforcement
discretion is appropriate with respect to premarket review and quality
system requirements whether the test is: (1) An LDT (designed,
manufactured and used within a single laboratory); (2) comprised of
only components and instruments that are legally marketed for clinical
use, which have a number of regulatory controls in place, including
reporting of adverse events; and (3) interpreted by laboratory
professionals who are appropriately qualified and trained as required
by the CLIA (Clinical Laboratory Improvement Amendments) regulations
(see, e.g., 42 CFR 493.1449), without the use of automated
instrumentation or software for interpretation? Are these three factors
also sufficient to support continued enforcement discretion in full
(i.e., for all regulatory requirements rather than just for premarket
review and quality system requirements) for this category of LDTs?
Should FDA instead consider different factors?
FDA has proposed the following three factors for
consideration of continued enforcement discretion for premarket review
and QS requirements for LDTs for Unmet Needs whether: (1) The device
meets the definition of an LDT (a test designed, manufactured and used
by a single laboratory); (2) there is no FDA cleared or approved IVD
available for that specific intended use; and (3) the LDT is both
manufactured and used by a healthcare facility laboratory (such as one
located in a hospital or clinic) for a patient that is being diagnosed
and/or treated at that same healthcare facility or within
[[Page 69863]]
that facility's healthcare system. Are these factors appropriate and/or
sufficient to both mitigate risks and to provide patient access if
warranted? Should FDA use different factors to best balance patient
safety and patient access?
For the categories of Traditional LDTs and LDTs for Unmet
Needs, one of the factors for enforcement discretion is whether the LDT
is both manufactured and used by a healthcare facility laboratory (such
as one located in a hospital or clinic) for a patient that is being
diagnosed and/or treated at that same healthcare facility, or within
the facility's healthcare system. To further clarify this factor, the
Framework draft guidance document explains that ``healthcare system''
refers to a collection of hospitals that are owned and operated by the
same entity and that share access to patient care information for their
patients, such as, but not limited to, drug order information,
treatment and diagnosis information, and patient outcomes. If this is
an appropriate factor to use, are the considerations about which types
of facilities would or would not be included within a healthcare system
as defined by the draft guidance appropriate? Is there an alternative
definition of healthcare system that would be more appropriate?
Do the FDA-proposed categories for continued enforcement
discretion appropriately encompass the LDTs that should remain under
enforcement discretion? Should the scope of proposed categories be
broadened or narrowed? If so, how? Should additional categories for
continued enforcement discretion be added or proposed categories
removed? If so, which categories? For any new proposed categories, what
are the appropriate factors in considering enforcement discretion?
Is the information provided detailed enough for
laboratories to make a determination that their LDT falls within one of
these categories of continued enforcement discretion?
Session 4: Notification and Adverse Event Reporting (MDRs)
Will notification be adequate to provide FDA,
laboratories, providers, patients, and other members of the public a
comprehensive list of what tests are currently available for a specific
intended use?
Would it be sufficient to allow laboratory networks (i.e.,
more than one laboratory under the control of the same parent entity)
that offer the same test in multiple laboratories throughout their
network to submit a single notification for that test?
Are there certain types of LDTs for which the Agency
should neither enforce requirements for registration and listing nor
request notification in lieu of registration and listing?
How can FDA leverage other information in the community to
reduce the information collection associated with notification for
laboratories while still obtaining sufficient information to inform the
LDT classification and prioritization process?
Session 5: Public Process for Classification and Prioritization
How should FDA structure the advisory panels that will be
convened to provide input to help FDA classify LDTs and prioritize them
for enforcement of FDA premarket review requirements?
Which stakeholders should be able to present relevant
information or views at the panel meetings to discuss the
classification and prioritization of LDTs?
What factors should be considered in determining LDT
classification and risk?
How should the advisory panel process weigh these factors
when providing input for classifying LDTs and prioritizing LDTs for
enforcement of FDA premarket review requirements?
Session 6: Quality System Regulation
How can laboratories best leverage their current processes
and procedures, implemented to meet CLIA accreditation requirements, to
meet the FDA QS regulation requirements in the least burdensome manner?
Are there FDA QS requirements that differ from CLIA
requirements that FDA should continue not to enforce for laboratories
that make LDTs?
What additional resources will laboratories need in order
to assist them with implementation of the QS regulation?
What is the appropriate timeframe for phase-in enforcement
of QS regulation requirements in general and for design controls
specifically?
Dated: November 17, 2014.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2014-27713 Filed 11-21-14; 8:45 am]
BILLING CODE 4164-01-P