[Federal Register: March 16, 2004 (Volume 69, Number 51)]
[Rules and Regulations]
[Page 12271-12273]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr16mr04-5]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 864
[Docket No. 2004P-0044]
Medical Devices; Hematology and Pathology Devices; Classification
of the Factor V Leiden DNA Mutation Detection Systems Devices
AGENCY: Food and Drug Administration, HHS.
ACTION: Final rule.
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SUMMARY: The Food and Drug Administration (FDA) is classifying the
Factor V Leiden deoxyribonucleic acid (DNA) mutation detections systems
device into class II (special controls). The special control that will
apply to the device is the guidance document entitled ``Class II
Special Controls Guidance Document: Factor V Leiden DNA Mutation
Detection Systems.'' The agency is taking this action in response to a
petition submitted under the Federal Food, Drug, and Cosmetic Act (the
act) as amended by the Medical Device Amendments of 1976 (the 1976
amendments), the Safe Medical Devices Act of 1990 (SMDA), the Food and
Drug Administration Modernization Act of 1997 (FDAMA), and the Medical
Device User Fee and Modernization Act of 2002. The agency is
classifying this device into class II (special controls) in
[[Page 12272]]
order to provide a reasonable assurance of safety and effectiveness of
the device. Elsewhere in this issue of the Federal Register, FDA is
publishing a notice of availability of a guidance document that is the
special control for this device.
DATES: This rule is effective April 15, 2004. The classification was
effective December 17, 2003.
FOR FURTHER INFORMATION CONTACT: Elizabeth Mansfield, Center for
Devices and Radiological Health (HFZ-440), Food and Drug
Administration, 2098 Gaither Rd., Rockville, MD 20850, 301-594-1293.
SUPPLEMENTARY INFORMATION:
I. Background
In accordance with section 513(f)(1) of the act (21 U.S.C.
360c(f)(1)), devices that were not in commercial distribution before
May 28, 1976, the date of enactment of the 1976 amendments, generally
referred to as postamendments devices, are classified automatically by
statute into class III without any FDA rulemaking process. These
devices remain in class III and require premarket approval, unless and
until the device is classified or reclassified into class I or II or
FDA issues an order finding the device to be substantially equivalent,
in accordance with section 513(i) of the act, to a predicate device
that does not require premarket approval. The agency determines whether
new devices are substantially equivalent to previously marketed devices
by means of premarket notification procedures in section 510(k) of the
act (21 U.S.C. 360(k)) and 21 CFR part 807 of FDA's regulations.
Section 513(f)(2) of the act provides that any person who submits a
premarket notification under section 510(k) of the act for a device
that has not previously been classified may, within 30 days after
receiving written notice classifying the device in class III under
section 513(f)(1) of the act, request FDA to classify the device under
the criteria set forth in section 513(a)(1) of the act. FDA shall,
within 60 days of receiving such a request, classify the device by
written order. This classification shall be the initial classification
of the device. Within 30 days after the issuance of an order
classifying the device, FDA must publish a notice in the Federal
Register announcing such classification (513(f)(2) of the act).
In accordance with section 513(f)(1) of the act, FDA issued a
notice on December 5, 2003, classifying the Factor V Leiden Kit into
class III because it was not substantially equivalent to a device that
was introduced or delivered for introduction into interstate commerce
for commercial distribution before May 28, 1976, or a device which was
subsequently reclassified into class I or class II. On December 8,
2003, Roche Diagnostics Corp. submitted a petition requesting
classification of the Factor V Leiden Kit under section 513(f)(2) of
the act. The manufacturer recommended that the device be classified
into class II.
In accordance with 513(f)(2) of the act, FDA reviewed the petition
in order to classify the device under the criteria for classification
set forth in 513(a)(1) of the act. Devices are to be classified into
class II if general controls, by themselves, are insufficient to
provide reasonable assurance of safety and effectiveness, but there is
sufficient information to establish special controls to provide
reasonable assurance of the safety and effectiveness of the device for
its intended use. After review of the information submitted in the
petition, FDA determined that the Factor V Leiden system intended for
use for the detection of the G1691A mutation in patients with suspected
thrombophilia can be classified in class II with the establishment of
special controls. FDA believes these special controls, in addition to
the general controls, will provide reasonable assurance of safety and
effectiveness of the device.
The device is assigned the generic name Factor V Leiden DNA
mutation detection system and is identified as a device that consists
of different reagents and instruments, which include polymerase chain
reaction (PCR) primers, hybridization matrices, thermal cyclers,
imagers, and software packages. The detection system is intended as an
aid in the diagnosis of patients with suspected thrombophilia.
FDA has identified no direct risks to patient health when tests are
used as an aid to diagnosis. However, failure of the test to perform as
indicated or error in interpretation of results may lead to improper
medical management of patients with clotting disorders. A false
negative interpretation could lead to undermanagement of the patient,
with increased risk of future thrombotic events. A false positive
result could lead to inappropriate treatment and alteration of present
and future drug selection and treatment. Consequently, FDA has
identified the following risks to health associated specifically with
this type of device: (1) Improper medical management; and (2)
misdiagnosis and improper treatment, and drug selection and dosing.
Therefore, in addition to the general controls of the act, the device
is subject to special controls, identified as the guidance document
entitled ``Class II Special Controls Guidance Document: Factor V Leiden
DNA Mutation Detection Systems.''
The class II special controls guidance document provides
information on how to meet premarket (510(k)) submission requirements
for the device, including recommendations on instrumentation
validation, reproducibility, use of control materials, and clinical
studies or literature summaries. The premarket notification should
describe the risk analysis method. FDA believes that following the
class II special controls guidance document addresses the risks to
health identified in the previous paragraph. Therefore, on December 17,
2003, FDA issued an order to the petitioner classifying the device into
class II. FDA is codifying this classification by adding Sec.
864.7280.
Following the effective date of this final classification rule, any
firm submitting a 510(k) premarket notification for a Factor V Leiden
DNA mutation detection systems device will need to address the issues
covered in the special control guidance. However, the firm need only
show that its device meets the recommendations of the guidance or in
some other way provides equivalent assurance of safety and
effectiveness.
Section 510(m) of the act provides that FDA may exempt a class II
device from the premarket notification requirements under section
510(k) of the act, if FDA determines that premarket notification is not
necessary to provide reasonable assurance of the safety and
effectiveness of the device. For this type of device, FDA has
determined that premarket notification is necessary to provide
reasonable assurance of safety and effectiveness; therefore, the device
is not exempt from premarket notification requirements. The device is
used to test for the Factor V Leiden DNA mutation in the Factor V gene
as an aid in the diagnosis of patients with suspected thrombophilia.
FDA review of key performance characteristics, test methodology, and
other relevant performance data, with regard to the test's sensitivity,
specificity, and reproducibility, will ensure that acceptable levels of
performance for both safety and effectiveness will be addressed before
market clearance. Thus, persons who intend to market this type of
device must submit to FDA a premarket notification containing
information on the Factor V Leiden DNA mutation detection systems
device before marketing the device.
FDA is also adding paragraph (d) to 21 CFR 864.1 to advise
interested persons where to find guidance documents referenced in 21
CFR part 864, including the special controls
[[Page 12273]]
guidance document identified in this rule.
II. Environmental Impact
The agency has determined under 21 CFR 25.22 and 25.34(b) that this
action is of a type that does not individually or cumulatively have a
significant effect on the human environment. Therefore, neither an
environmental assessment nor an environmental impact statement is
required.
III. Analysis of Impacts
FDA has examined the impacts of the final rule under Executive
Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612), and
the Unfunded Mandates Reform Act of 1995 (Public Law 104-4). Executive
Order 12866 directs agencies to assess all costs and benefits of
available regulatory alternatives and, when regulation is necessary, to
select regulatory approaches that maximize net benefits (including
potential economic, environmental, public health and safety, and other
advantages; distributive impacts; and equity). The agency believes that
this final rule is consistent with the regulatory philosophy and
principles identified in the Executive order. In addition, the final
rule is not a significant regulatory action as defined by the Executive
order and so it is not subject to review under the Executive order.
The Regulatory Flexibility Act requires agencies to analyze
regulatory options that would minimize any significant impact of a rule
on small entities. Classification of these devices into class II will
relieve manufacturers of the device of the cost of complying with the
premarket approval requirements of section 515 of the act (21 U.S.C.
360e), and may permit small potential competitors to enter the
marketplace by lowering their costs. The agency, therefore, certifies
that the final rule will not have a significant impact on a substantial
number of small entities. In addition, this final rule will not impose
costs of $100 million or more on either the private sector or State,
local, and tribal governments in the aggregate and, therefore, a
summary statement of analysis under section 202(a) of the Unfunded
Mandates Reform Act is not required.
IV. Federalism
FDA has analyzed this final rule in accordance with the principles
set forth in Executive Order 13132. FDA has determined that the rule
does not contain policies that have substantial direct effects on the
States, on the relationship between the National Government and the
States, or on the distribution of power and responsibilities among the
various levels of government. Accordingly, the agency has concluded
that the rule does not contain policies that have federalism
implications as defined in the Executive order and, consequently, a
federalism summary impact statement is not required.
V. Paperwork Reduction Act of 1995
This final rule contains no collections of information. Therefore,
clearance by the Office of Management and Budget under the Paperwork
Reduction Act of 1995 is not required.
VI. Reference
The following reference has been placed on display in the Division
of Dockets Management (HFA-305), Food and Drug Administration, 5630
Fishers Lane, rm. 1061, Rockville, MD 20852, and may be seen by
interested persons between 9 a.m. and 4 p.m., Monday through Friday.
1. Petition from Roche Diagnostics Corp., dated December 8,
2003.
List of Subjects in 21 CFR Part 864
Medical devices.
0
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, 21 CFR part
864 is amended as follows:
PART 864--HEMATOLOGY AND PATHOLOGY DEVICES
0
1. The authority citation for 21 CFR part 864 continues to read as
follows:
Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 371.
0
2. Section 864.1 is amended by adding paragraph (d) to read as follows:
Sec. 864.1 Scope.
* * * * *
(d) Guidance documents referenced in this part are available on the
Internet at http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cdrh/guidance.html.
0
3. Section 864.7280 is added to subpart H to read as follows:
Sec. 864.7280 Factor V Leiden DNA mutation detection systems.
(a) Identification. Factor V Leiden deoxyribonucleic acid (DNA)
mutation detection systems are devices that consist of different
reagents and instruments which include polymerase chain reaction (PCR)
primers, hybridization matrices, thermal cyclers, imagers, and software
packages. The detection of the Factor V Leiden mutation aids in the
diagnosis of patients with suspected thrombophilia.
(b) Classification. Class II (special controls). The special
control is FDA's guidance entitled ``Class II Special Controls Guidance
Document: Factor V Leiden DNA Mutation Detection Systems.'' (See Sec.
864.1(d) for the availability of this guidance document.)
Dated: March 5, 2004.
Beverly Chernaik Rothstein,
Acting Deputy Director for Policy and Regulations, Center for Devices
and Radiological Health.
[FR Doc. 04-5864 Filed 3-15-04; 8:45 am]
BILLING CODE 4160-01-S