[Federal Register: January 2, 2009 (Volume 74, Number 1)]
[Rules and Regulations]
[Page 6-8]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr02ja09-4]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 866
[Docket No. FDA-2008-N-0517]
Medical Devices; Immunology and Microbiology Devices;
Classification of Enterovirus Nucleic Acid Assay
AGENCY: Food and Drug Administration, HHS.
ACTION: Final rule.
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SUMMARY: The Food and Drug Administration (FDA) is classifying
enterovirus nucleic acid assay 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: Nucleic Acid
Amplification Assay for the Detection of Enterovirus RNA'' (ribonucleic
acid). The agency is classifying the device into class II (special
controls) in order to provide a
[[Page 7]]
reasonable assurance of safety and effectiveness of the device.
Elsewhere in this issue of the Federal Register, FDA is announcing the
availability of the guidance document that will serve as the special
control for this device.
DATES: This final rule is effective February 2, 2009. The
classification was effective March 16, 2007.
FOR FURTHER INFORMATION CONTACT: Uwe Scherf, Center for Devices and
Radiological Health (HFZ-440), Food and Drug Administration, 2098
Gaither Rd., Rockville, MD 20850, 240-276-0725.
SUPPLEMENTARY INFORMATION:
I. What is the Background of This Rulemaking?
In accordance with section 513(f)(1) of the Federal Food, Drug, and
Cosmetic Act (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 Medical Device Amendments of 1976 (the 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 predicate devices by means
of premarket notification procedures in section 510(k) of the act (21
U.S.C. 360(k)) and part 807 (21 CFR part 807).
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 an order classifying the device in class III under section
513(f)(1), request FDA to classify the device under the criteria set
forth in section 513(a)(1). 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 (section
513(f)(2) of the act).
In accordance with section 513(f)(1) of the act, FDA issued an
order on March 9, 2007, classifying the Xpert EVTM Assay as
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 that was
subsequently reclassified into class I or class II. Cepheid submitted a
petition dated March 9, 2007, requesting classification of the Xpert
EVTM Assay under section 513(f)(2) of the act. FDA filed the
petition on March 12, 2007. The manufacturer recommended that the
device be classified into class II.
In accordance with section 513(f)(2) of the act, FDA reviewed the
petition in order to classify the device under the criteria for
classification set forth in section 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 Xpert
EVTM Assay can be classified in class II with the
establishment of special controls. FDA believes these special controls,
in addition to general controls, will provide reasonable assurance of
safety and effectiveness of the device.
The device is assigned the generic name ``enterovirus nucleic acid
assay.'' It is identified as a device that consists of primers, probes,
enzymes, and controls for the amplification and detection of
enterovirus RNA in cerebrospinal fluid (CSF) from individuals who have
signs and symptoms consistent with meningitis or meningoencephalitis.
The detection of enterovirus RNA, in conjunction with other laboratory
tests, aids in the clinical laboratory diagnosis of viral meningitis
caused by enterovirus.
Failure of nucleic acid assays for detection of enterovirus RNA to
perform as expected, or failure to interpret results correctly, may
lead to incorrect patient management decisions. A false negative report
could lead to delays in providing (or even failure to provide) a
definitive diagnosis, and the unnecessary treatment of the patient with
antibiotics. A false positive report could lead to a delayed treatment
of bacterial meningitis or other forms of meningitis. This delayed
treatment due to a false positive result could cause progression of
potentially life-threatening bacterial meningitis with subsequent
severe morbidity to the patient and potentially even patient death.
Device failure leading to no result (for example, due to failure of
reagents, instrumentation, data management, or software) or an invalid
or equivocal result could delay diagnosis, and could require an
additional collection of CSF fluid, a procedure that is associated with
the risk of infection. Furthermore, the appearance of new serotypes of
enterovirus may affect the performance of an enterovirus nucleic acid
amplification assay for the detection of enterovirus RNA in CSF
specimens. Primers and probes for detection of enteroviruses are
selected for their homology with highly conserved regions within viral
RNA segments that are present in most enterovirus serotypes. Primers
and probes might not detect new serotypes that appear over time. In
addition, test performance can be affected, as the epidemiology and
pathology of disease caused by the new enterovirus serotypes could
change.
FDA believes the class II special controls guidance document will
aid in mitigating potential risks by providing recommendations on
labeling and validation of performance characteristics. The guidance
document also provides information on how to meet premarket (510(k))
submission requirements for the device. FDA believes that following the
class II special controls guidance document generally addresses the
risks to health identified in the previous paragraph. Therefore, on
March 16, 2007, FDA issued an order to the petitioner classifying the
device into class II. FDA is codifying this classification by adding
Sec. 866.3225.
Following the effective date of this final classification rule, any
firm submitting a 510(k) premarket notification for an enterovirus
nucleic acid assay will need to address the issues covered in the
special controls 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, however, FDA has
determined that premarket review of the system's key performance
characteristics, test methodology, labeling, and other requirements as
outlined in Sec. 807.87, will provide reasonable assurance that
acceptable levels of performance for both safety and effectiveness will
be addressed before marketing clearance. Thus, persons who intend to
market this type
[[Page 8]]
of device must submit to FDA a premarket notification, prior to
marketing the device, which contains information about the gene
expression profiling test system for breast cancer prognosis they
intend to market.
II. What is the Environmental Impact of This Rule?
The agency has determined under 21 CFR 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. What is the Economic Impact of This Rule?
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 not a significant regulatory action as defined by
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. Because classification of this device type 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 certifies
that the final rule will not have a significant economic impact on a
substantial number of small entities.
Section 202(a) of the Unfunded Mandates Reform Act of 1995 requires
that agencies prepare a written statement, which includes an assessment
of anticipated costs and benefits, before proposing ``any rule that
includes any Federal mandate that may result in the expenditure by
State, local, and tribal governments, in the aggregate, or by the
private sector, of $100,000,000 or more (adjusted annually for
inflation) in any one year.'' The current threshold after adjustment
for inflation is $130 million, using the most current (2007) Implicit
Price Deflator for the Gross Domestic Product. FDA does not expect this
final rule to result in any 1-year expenditure that would meet or
exceed this amount.
IV. Does This Final Rule Have Federalism Implications?
FDA has analyzed this final rule in accordance with the principles
set forth in Executive Order 13132. Section 4(a) of the Executive order
requires agencies to ``construe *** a Federal statute to preempt State
law only where the statute contains an express preemption provision or
there is some other clear evidence that the Congress intended
preemption of State law, or where the exercise of State authority
conflicts with the exercise of Federal authority under the Federal
statute. Federal law includes an express preemption provision that
preempts certain state requirements ``different from, or in addition
to'' certain federal requirements applicable to devices. See 21 U.S.C.
360k; Medtronic v. Lohr, 518 U.S. 470 (1996); Riegel v. Medtronic, 128
S.Ct. 999 (2008).
In this rulemaking, FDA has determined that general controls by
themselves are insufficient to provide reasonable assurance of the
safety and effectiveness of the device, and that there is sufficient
information to establish special controls to provide such assurance.
FDA has therefore imposed a special control to address the
amplification and detection of enterovirus RNA in CSF from individuals
who have signs and symptoms consistent with meningitis or
meningoencephalitis. The detection of enterovirus RNA, in conjunction
with other laboratory tests, aids in the clinical laboratory diagnosis
of viral meningitis caused by enterovirus.
As with any Federal requirement, if a State law requirement makes
compliance with both Federal law and State law impossible, or would
frustrate Federal objectives, the State requirement would be preempted.
See Geier v. American Honda Co., 529 U.S. 861, (2000); English v.
General Electric Co., 496 U.S. 72, 79 (1990), Florida Lime & Avocado
Growers, Inc., 373 U.S. 132, 142-143 (1963); Hines v. Davidowitz, 312
U.S. 52, 67 (1941).
V. How Does This Rule Comply With the Paperwork Reduction Act of 1995?
This final rule contains no collections of information. Therefore,
clearance by the Office of Management and Budget (OMB) under the
Paperwork Reduction Act of 1995 is not required. Elsewhere in this
issue of the Federal Register, FDA is issuing a notice announcing the
guidance for the final rule. This guidance entitled ``Class II Special
Controls Guidance Document: Nucleic Acid Amplification Assay for the
Detection of Enterovirus RNA'' references previously approved
collections of information found in FDA regulations.
VI. What References Are on Display?
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 Cepheid, dated March 9, 2007.
List of Subjects in 21 CFR Part 866
Biologics, Laboratories, 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
866 is amended as follows:
PART 866--IMMUNOLOGY AND MICROBIOLOGY DEVICES
0
1. The authority citation for 21 CFR part 866 continues to read as
follows:
Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 371.
0
2. Section 866.3225 is added to subpart D to read as follows:
Sec. 866.3225 Enterovirus nucleic acid assay.
(a) Identification. An enterovirus nucleic acid assay is a device
that consists of primers, probes, enzymes, and controls for the
amplification and detection of enterovirus ribonucleic acid (RNA) in
cerebrospinal fluid (CSF) from individuals who have signs and symptoms
consistent with meningitis or meningoencephalitis. The detection of
enterovirus RNA, in conjunction with other laboratory tests, aids in
the clinical laboratory diagnosis of viral meningitis caused by
enterovirus.
(b) Classification. Class II (special controls). The special
control is FDA's guidance document entitled ``Class II Special Controls
Guidance Document: Nucleic Acid Amplification Assay for the Detection
of Enterovirus RNA.'' See Sec. 866.1(e) for the availability of this
guidance document.
Dated: December 16, 2008.
Daniel G. Schultz,
Director, Center for Devices and Radiological Health.
[FR Doc. E8-31213 Filed 12-31-08; 8:45 am]
BILLING CODE 4160-01-S