[Federal Register Volume 69, Number 51 (Tuesday, March 16, 2004)]
[Rules and Regulations]
[Pages 12271-12273]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-5864]


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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

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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://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