[Federal Register: July 26, 2007 (Volume 72, Number 143)]
[Notices]
[Page 41081-41083]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr26jy07-57]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 2006D-0347]
Draft Guidance for Industry and Food and Drug Administration
Staff; In Vitro Diagnostic Multivariate Index Assays; 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availability of a revised draft guidance entitled ``In Vitro Diagnostic
Multivariate Index Assays.'' FDA is issuing this revised draft guidance
to address the definition and regulatory status of a class of In Vitro
Diagnostic Devices referred to as In Vitro Diagnostic Multivariate
Index Assays (IVDMIAs). The revised draft guidance also addresses
premarket and postmarket requirements with respect to IVDMIAs. The
initial draft of this guidance was issued September 7, 2006.
DATES: Submit written or electronic comments on this draft guidance by
August 27, 2007.
ADDRESSES: Submit written requests for single copies of the draft
guidance document entitled ``In Vitro Diagnostic Multivariate Index
Assays'' 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 or to the Office of Communication, Training, and Manufacturers
Assistance (HFM-40), Center for Biologics Evaluation and Research
(CBER), Food and Drug Administration, 1401 Rockville Pike, suite 200N,
Rockville, MD 20852-1448. Send one self-addressed adhesive label to
assist that office in processing your request, or fax your request to
240-276-3151. See the SUPPLEMENTARY INFORMATION section for information
on electronic access to the draft guidance.
Submit written comments concerning this draft guidance to the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: Courtney Harper, Center for Devices
and Radiological Health (HFZ-440), Food and Drug Administration, 2098
Gaither Rd., Rockville, MD 20850, 240-276-0694.
For further information concerning the guidance as it related to
devices regulated by CBER: Martin Ruta, Center for Biologics Evaluation
and Research, Food and Drug Administration, 1401 Rockville Pike,
Rockville, MD 20852, 301-827-3518.
SUPPLEMENTARY INFORMATION:
I. Background
In the Federal Register of September 7, 2006 (71 FR 52800). FDA
published a notice of availability of the initial draft guidance to
address the definition and regulatory status of a class of in vitro
diagnostic devices referred to as ``In Vitro Diagnostic Multivariate
Index Assays (IVDMIAs).'' The initial draft guidance also addressed
premarket and postmarket requirements with respect to IVDMIAs.
An IVDMIA, as defined in the draft guidance document, is a device
within the meaning of the Federal Food, Drug, and Cosmetic Act (the
act). Some IVDMIAs are laboratory-developed tests (LDTs); laboratory-
developed IVDMIAs are a specific subset of LDTs. While FDA has stated
that ``clinical laboratories that develop (in-house) tests
[[Page 41082]]
are acting as manufacturers of medical devices and are subject to FDA
jurisdiction under the Act,'' 62 FR 62243 to 62249 (November 21, 1997),
the agency has generally exercised enforcement discretion over most
standard LDTs. However, in the draft guidance, FDA recognizes that
IVDMIAs include elements that are not among the primary ingredients of
standard LDTs (e.g., complex, unique, interpretation functions).
IVDMIAs thus do not fall within the scope of LDTs over which FDA has
generally exercised enforcement discretion.
IVDMIAs raise significant issues of safety and effectiveness. These
types of tests are developed based on observed correlations between
multivariate data and clinical outcome, such that the clinical validity
of the claims is not transparent to patients, laboratorians, and
clinicians who order these tests. Additionally, IVDMIAs frequently have
a high risk intended use. FDA is concerned that patients and healthcare
practitioners are relying upon IVDMIAs with high risk intended uses to
make critical healthcare decisions without any independent assurance
that the IVDMIA has been properly clinically validated, and without any
ability to assess whether the test yields clinically valid results.
With this revised draft guidance document, FDA seeks to identify
IVDMIAs as a discrete category of device, and to clarify that, even
when offered as LDTs, IVDMIAs must meet pre- and post-market device
requirements under the act and FDA regulations, including premarket
review requirements in the case of most class II and III devices.
FDA received and considered approximately 60 sets of comments on
the initial draft guidance document, including comments provided at a
public meeting that was held on February 8, 2007. After taking the
comments into consideration, the FDA has updated the draft guidance
document to provide clarifications as needed.
Certain comments on the initial draft guidance document requested
that FDA undertake notice and comment rulemaking rather than issue a
guidance document in order to allow sufficient opportunity for public
input. In response to this concern, FDA extended the comment period on
the draft guidance document from 90 days to 180 days, March 5, 2007 (71
FR 68822), and held a public meeting to provide a forum for
presentations and comments on the draft guidance document. The meeting
was attended by 266 people representing a cross-section of interested
stakeholders including industry, consumer groups, and the medical
community. FDA has carefully considered the comments it has received.
Many comments reflect that stakeholders construed the definition of
IVDMIAs in the initial draft guidance document to encompass a wider
range of tests than FDA had intended. The initial draft guidance
document has been revised to clarify the definition of an IVDMIA and to
provide examples of tests that the agency does and does not consider to
be IVDMIAs. This section of the draft guidance was modified so that
stakeholders can more easily understand the nature of tests designated
as IVDMIAs, and manufacturers can more easily determine whether their
tests are IVDMIAs. However, the clarifications do not alter the scope
or intent of the definition of an IVDMIA found in the initial draft
guidance document.
In response to additional comments received, the revised draft
guidance document now clarifies FDA regulatory mechanisms in general,
such as how devices are classified and reviewed based on the risk of
the intended use, how laboratory-developed IVDMIAs should be labeled,
and how manufacturers can update and improve cleared or approved
devices using existing mechanisms within the regulatory framework.
These existing mechanisms enable manufacturers to bring innovative new
tests to the market and ensure that they can be updated and improved as
new scientific information becomes available. While this information is
generally available in existing regulations, guidance documents, and on
the FDA Web site, the revised draft guidance provides a summary of this
information with a focus on IVDMIAs in order to assist those
stakeholders who are not familiar with existing FDA requirements.
In other comments, some stakeholders expressed concern that
requiring FDA regulatory compliance for IVDMIAs has the potential to
discourage the development of new tests for rare diseases. A
manufacturer of an IVDMIA for a disease or condition that affects small
patient populations may find that research and development costs exceed
market returns. The draft guidance has been revised to indicate FDA's
intent to exercise enforcement discretion for laboratory-developed
IVDMIAs that are intended to diagnose rare diseases (i.e., IVDMIAs that
meet the definition of Humanitarian Use Devices under 21 CFR part 814
Subpart H).
Finally, the draft guidance document clarifies that laboratories
that manufacture IVDMIAs should follow the Medical Device Reporting
requirements for manufacturers, 21 CFR part 803 for their IVDMIA
device(s). As in the initial draft guidance, the revised draft guidance
indicates that FDA intends to issue guidance to assist laboratories
that manufacture IVDMIAs in complying with the Quality System
regulation (QS), 21 CFR part 820. In response to comments that
expressed concern about coming into compliance with the QS regulation,
the revised draft guidance indicates that until such a final guidance
is published, FDA intends to exercise enforcement discretion with
regard to post-market QS requirement enforcement for laboratories that
manufacture IVDMIAs, recognizing that some Clinical Laboratory
Improvement Amendments of 1988 (CLIA' 88) requirements may partially
fulfill corresponding QS regulation requirements.
FDA is issuing this revised draft in order to gather significant
new comments before issuing a final version of the guidance. Because
the agency believes it has addressed the most important concerns raised
by the comments it received on the initial draft, and because it is
important to issue a final guidance to provide clarity for
stakeholders, FDA is providing a comment period of 30 days following
publication of this document.
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
represents the agency's current thinking on IVDMIAs. 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 using the Internet. To receive ``In Vitro Diagnostic Multivariate
Index Assays,'' you may either send an e-mail request to
dsmica@fda.hhs.gov to receive an electronic copy of the document or
send a fax request to 240-276-3151 to receive a hard copy. Please use
the document number 1610 to identify the guidance you are requesting.
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
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Register reprints, information on premarket submissions (including
lists of approved applications and manufacturers' addresses), small
manufacturers' 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 CBER Internet site at http://www.fda.gov/cber/.
guidelines.htm or on the Division of Dockets Management Internet site
at http://www.fda.gov/ohrms/dockets.
IV. Paperwork Reduction Act of 1995
This draft 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
collections of information in the draft guidance document have been
approved by OMB in accordance with the PRA under the regulations
governing premarket notifications (21 CFR part 807, subpart E, OMB
control number 0910-0120) premarket approval applications (21 CFR part
814, OMB control number 0910-0231), investigational device exemptions
(21 CFR part 812, OMB control number 0910-0078), quality system
regulation (21 CFR part 820, OMB control number 0910-0073), and medical
device reporting (21 CFR part 803, OMB control number 0910-0437). The
labeling provisions addressed in this guidance have been approved by
OMB under OMB control number 0910-0485.
V. Comments
Interested persons may submit to the Division of Dockets Management
(see ADDRESSES), written or electronic comments regarding this document
on or before August 27, 2007. Submit electronic comments to http://www.fda.gov/dockets/ecomments.
Submit two paper copies of any mailed
comments, except that individuals may submit one copy. Comments are to
be identified with the docket number found in brackets in the heading
of this document. Comments received may be seen in the Division of
Dockets Management between 9 a.m. and 4 p.m., Monday through Friday.
Dated: July 20, 2007.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 07-3660 Filed 7-23-07; 12:02 pm]
BILLING CODE 4160-01-S