[Federal Register Volume 79, Number 99 (Thursday, May 22, 2014)]
[Proposed Rules]
[Pages 29387-29392]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2014-11635]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 866
[Docket No. FDA-2014-N-0440]
Microbiology Devices; Reclassification of Influenza Virus Antigen
Detection Test Systems Intended for Use Directly With Clinical
Specimens
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed order.
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SUMMARY: The Food and Drug Administration (FDA) is proposing to
reclassify antigen based rapid influenza virus antigen detection test
systems intended to detect influenza virus directly from clinical
specimens that are currently regulated as influenza virus serological
reagents from class I into class II with special controls and into a
new device classification regulation.
DATES: Submit either electronic or written comments on the proposed
order by August 20, 2014. See section XI for the proposed effective
date of any final order that may publish based on this proposed order.
ADDRESSES: You may submit comments, identified by Docket No. FDA-2014-
N-0440, by any of the following methods:
Electronic Submissions
Submit electronic comments in the following way:
Federal eRulemaking Portal: http://www.regulations.gov.
Follow the instructions for submitting comments.
Written Submissions
Submit written submissions in the following ways:
Mail/Hand delivery/Courier (for paper submissions):
Division of Dockets Management (HFA-305), Food and Drug Administration,
5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
Instructions: All submissions received must include the Agency name
and Docket No. FDA-2014-N-0440 for this rulemaking. All comments
received may be posted without change to http://www.regulations.gov,
including any personal information provided. For additional information
on submitting comments, see the ``Comments'' heading of the
SUPPLEMENTARY INFORMATION section.
Docket: For access to the docket to read background documents or
comments received, go to http://www.regulations.gov and insert the
docket number, found in brackets in the heading of this document, into
the ``Search'' box and follow the prompts and/or go to the Division of
Dockets Management, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT: Stefanie Akselrod, Center for Devices
and Radiological Health, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 66, Rm. 5517, Silver Spring, MD 20993-0002, 301-
796-6188.
SUPPLEMENTARY INFORMATION:
I. Regulatory Authorities
The Federal Food, Drug, and Cosmetic Act (the FD&C Act), as amended
by the Medical Device Amendments of 1976 (the 1976 amendments) (Pub. L.
94-295), the Safe Medical Devices Act of 1990 (Pub. L. 101-629), and
the Food and Drug Administration Modernization Act of 1997 (FDAMA)
(Pub. L. 105-115), the Medical Device User Fee and Modernization Act of
2002 (Pub. L. 107-250), the Medical Devices Technical Corrections Act
(Pub. L. 108-214), the Food and Drug Administration Amendments Act of
2007 (Pub. L. 110-85), and the Food and Drug Administration Safety and
Innovation Act (FDASIA) (Pub. L. 112-144), among other amendments,
established a comprehensive system for the regulation of medical
devices intended for human use. Section 513 of the FD&C Act (21 U.S.C.
360c) established three categories (classes) of devices, reflecting the
regulatory controls needed to provide reasonable assurance of their
safety and effectiveness. The three categories of devices are class I
(general controls), class II (special controls), and class III
(premarket approval).
Under the FD&C Act, FDA clears or approves the three classes of
medical devices for commercial distribution in the United States
through three regulatory processes: Premarket approval (PMA), product
development protocol, and premarket notification (a premarket
notification is generally referred to as a ``510(k)'' after the section
of the FD&C Act where the requirement is found). The purpose of a
premarket notification is to demonstrate that the new device is
substantially equivalent to a legally marketed predicate device. Under
section 513(i) of the FD&C Act, a device is substantially equivalent if
it has the same intended use and technological characteristics as a
predicate device, or has different technological characteristics but
data demonstrate that the new device is as safe and effective as the
predicate device and does not raise different issues of safety or
effectiveness.
FDA determines whether new devices are substantially equivalent to
previously offered devices by means of premarket notification
procedures in section 510(k) of the FD&C Act (21 U.S.C. 360(k)) and
part 807 of the regulations (21 CFR part 807). Section 510(k) of the
FD&C Act and the implementing regulations in part 807, subpart E,
require a person who intends to market a medical device to submit a
premarket notification submission to FDA before proposing to begin the
introduction, or delivery for introduction into interstate commerce,
for commercial distribution of a device intended for human use.
In accordance with section 513(f)(1) of the FD&C Act, devices that
were not in commercial distribution before May 28, 1976, the date of
enactment of the 1976 amendments, generally referred to as
postamendment 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 FDA classifies the
device into class I or class II by issuing an order finding the device
to be substantially equivalent, in accordance with section 513(i) of
the FD&C Act, to a predicate device that does not require premarket
approval or the device is reclassified into class I or class II. The
Agency determines whether new devices are substantially equivalent to
predicate devices by means of premarket notification procedures in
section 510(k) of the FD&C Act and part 807 of FDA's regulations.
Section 513(f)(2) of the FD&C Act establishes procedures for ``de
novo'' risk-based review and classification of postamendment devices
automatically classified into class III by section
[[Page 29388]]
513(f)(1). Under these procedures, any person whose device is
automatically classified into class III by section 513(f)(1) of the
FD&C Act may seek reclassification into class I or II, either after
receipt of an order finding the device to be not substantially
equivalent, in accordance with section 513(i), to a predicate device
that does not require premarket approval, or at any time after
determining there is no legally marketed device upon which to base a
determination of substantial equivalence. In addition, under section
513(f)(3) of the FD&C Act, FDA may initiate, or the manufacturer or
importer of a device may petition for, the reclassification of a device
classified into class III under section 513(f)(1).
On July 9, 2012, FDASIA was enacted. Section 608(a) of FDASIA (126
Stat. 1056) amended section 513(e) of the FD&C Act, changing the
process for reclassifying a device from rulemaking to an administrative
order. Section 608(b) of FDASIA (126 Stat. 1056) amended section 515(b)
of the FD&C Act (21 U.S.C. 360e(b)), changing the process for requiring
premarket approval for a preamendments class III device from rulemaking
to an administrative order.
Reclassification
FDA is publishing this document to propose the reclassification of
antigen based rapid influenza detection test (RIDT) systems intended to
detect influenza virus antigen directly from clinical specimens that
are currently regulated as influenza virus serological reagents under
Sec. 866.3330 (21 CFR 866.3330) from class I into class II with
special controls and into a new device classification regulation.
Section 513(e) of the FD&C Act governs reclassification of
classified preamendments device types and postamendments devices that
have been classified into class I or II under section 513(f)(2) or
(f)(3) of the FD&C Act. This section provides that FDA may, by
administrative order, reclassify a device based upon ``new
information.'' FDA can initiate a reclassification under section 513(e)
of the FD&C Act or an interested person may petition FDA to reclassify
an eligible device type. The term ``new information,'' as used in
section 513(e) of the FD&C Act, includes information developed as a
result of a reevaluation of the data before the Agency when the device
was originally classified, as well as information not presented, not
available, or not developed at that time. (See, e.g., Holland-Rantos
Co. v. United States Department of Health, Education, and Welfare, 587
F.2d 1173, 1174 n.1 (D.C. Cir. 1978); Upjohn v. Finch, 422 F.2d 944
(6th Cir. 1970); Bell v. Goddard, 366 F.2d 177 (7th Cir. 1966).)
Reevaluation of the data previously before the Agency is an
appropriate basis for subsequent action where the reevaluation is made
in light of newly available authority (see Bell, 366 F.2d at 181;
Ethicon, Inc. v. FDA, 762 F.Supp. 382, 388-391 (D.D.C. 1991)), or in
light of changes in ``medical science'' (Upjohn, 422 F.2d at 951).
Whether data before the Agency are old or new data, the ``new
information'' to support reclassification under section 513(e) of the
FD&C Act must be ``valid scientific evidence,'' as defined in section
513(a)(3) and 21 CFR 860.7(c)(2). (See, e.g., General Medical Co. v.
FDA, 770 F.2d 214 (D.C. Cir. 1985); Contact Lens Association v. FDA,
766 F.2d 592 (D.C. Cir.), cert. denied, 474 U.S. 1062 (1986).)
FDA relies upon ``valid scientific evidence'' in the classification
process to determine the level of regulation for devices. To be
considered in the reclassification process, the ``valid scientific
evidence'' upon which the Agency relies must be publicly available.
Publicly available information excludes trade secret and/or
confidential commercial information, e.g., the contents of a pending
PMA. (See section 520(c) of the FD&C Act (21 U.S.C. 360j(c)).) Section
520(h)(4) of the FD&C Act, added by FDAMA, provides that FDA may use,
for reclassification of a device, certain information in a PMA 6 years
after the application has been approved. This can include information
from clinical and preclinical tests or studies that demonstrate the
safety or effectiveness of the device but does not include descriptions
of methods of manufacture or product composition and other trade
secrets.
Section 513(e)(1) of the FD&C Act sets forth the process for
issuing a final order for reclassifying a device. Specifically, prior
to the issuance of a final order reclassifying a device, the following
must occur: (1) Publication of a proposed order in the Federal
Register; (2) a meeting of a device classification panel described in
section 513(b) of the FD&C Act; and (3) consideration of comments to a
public docket. FDA has held a meeting of a device classification panel
described in section 513(b) of the FD&C Act with respect to rapid
influenza diagnostic tests, and therefore, has met this requirement
under section 513(e).
FDAMA added section 510(m) to the FD&C Act. Section 510(m) of the
FD&C Act provides that a class II device may be exempted from the
premarket notification requirements under section 510(k) of the FD&C
Act, if the Agency determines that premarket notification is not
necessary to assure the safety and effectiveness of the device.
II. Regulatory Background of the Device
In the Federal Register of April 22, 1980 (45 FR 27204), FDA
published proposed regulations containing general provisions applicable
to the classification of immunology and microbiology devices and
individual proposed regulations to classify 161 immunology and
microbiology devices into one or more of three regulatory classes:
Class I (general controls), class II (performance standards), and class
III (premarket approval). These regulations included the April 22,
1980, proposed rule (45 FR 27204 at 27261) to classify influenza virus
serological reagents into class I under Sec. 866.3330 (21 CFR
866.3330) Influenza virus serological reagents. In a final rule, on
November 9, 1982 (47 FR 50814 at 50823), under the authority of the
Medical Device Amendments of 1976, FDA classified influenza virus
serological reagents into class I under Sec. 866.3330. At that time,
influenza tests conceived to fall under this regulation were laboratory
methods to detect antibodies that develop in response to influenza
infection while the detection of the influenza virus itself was done
primarily by viral culture. As enzyme immunoassay technology developed,
tests capable of detecting viral proteins (antigens) directly in human
respiratory samples began to come to FDA for clearance. Since then,
numerous influenza detection tests based on antigen-antibody binding
properties have been developed and cleared for the market. The first
RIDT for use directly from clinical specimens was cleared in 1990 and
followed by others in the late 1990s. To date, methods utilizing
antigens and antibodies as components of an influenza detection device
have been regulated under Sec. 866.3330 as class I devices exempt from
the premarket notification (510(k)) requirement subject to the
limitations in Sec. 866.9 (21 CFR 866.9). RIDTs found under Sec.
866.3330 exceed the limitations to the exemption from premarket
notification for influenza virus serological reagents under Sec.
866.9(c)(6) and thus require a 510(k) submission.
There are approximately 12 RIDTs classified under Sec. 866.3330
actively marketed today. Because these devices are easy to use and
provide results within 15 to 30 minutes, they are widely used in point-
of-care settings where rapid diagnosis of influenza is important for
early case identification.
[[Page 29389]]
III. Identification
We are proposing that RIDTs classified under Sec. 866.3330 be
identified under the new name of influenza virus antigen detection test
system. An influenza virus antigen detection test system is a device
intended for the qualitative detection of influenza viral antigens
directly from clinical specimens in patients with signs and symptoms of
respiratory infection. The test aids in the diagnosis of influenza
infection and provides epidemiological information on influenza. Due to
the propensity of the virus to mutate, new strains emerge over time
that may potentially affect the performance of these devices. Because
influenza is highly contagious and may lead to an acute respiratory
tract infection causing severe illness and even death, the accuracy of
these devices has serious public health implications.
IV. Background for Proposed Reclassification Decision
On June 13, 2013, FDA convened a meeting of the Microbiology
Advisory Panel to discuss the regulation of RIDTs that are currently
regulated as class I devices. The primary reasons for convening the
panel to discuss this topic were continued reports of poor real world
RIDT performance by the RIDTs in the field compounded by the emergence
of new influenza strains with a potential to create a public health
emergency. The occurrence of the 2009 flu pandemic emphasized that
these RIDTs, while widely used by clinicians in point of care settings,
performed poorly resulting in misdiagnosed cases and, according to
anecdotal reports, sometimes with serious or even fatal consequences.
The panel discussion included a discussion of the labeled
performance of the currently available RIDTs and presentations by
representatives from the Centers for Disease Control and Prevention
(CDC) and the Association of Public Health Laboratories (APHL) citing
the evidence of performance of these tests in real life settings. One
of the important issues raised was that the performance of an influenza
antigen detecting test is subject to the changes in the virus as it
mutates over time. The panel members were asked to discuss whether
there is sufficient evidence to suggest that general controls under
class I regulation are or are not sufficient to provide a reasonable
assurance that current and future RIDTs are safe and effective and
whether the addition of special controls would provide reasonable
assurance of the device's safety and effectiveness if the general
controls alone do not. Panel members provided the opinion that
sufficient data and information exist to indicate that special controls
are needed to mitigate the risks of false positive and false negative
results from RIDTs and provide a reasonable assurance of safety and
effectiveness of the device and to identify the special controls
needed. The panel members indicated that placing RIDTs into class II
with special controls was appropriate.
V. Classification Recommendation
FDA is proposing that all RIDTs currently regulated under Sec.
866.3330 be reclassified into class II with special controls under the
new device name ``influenza virus antigen detection test system.'' FDA
believes that special controls that: (1) Identify the minimum
acceptable performance criteria; (2) identify the appropriate
comparator for establishing performance of new assays; and (3) call for
mandatory annual analytical reactivity testing of contemporary
influenza strains, including testing of newly emerging strains that
pose a danger of public health emergency, would provide reasonable
assurance of safety and effectiveness of these devices.
Section 510(m) of the FD&C Act provides that a class II device may
be exempt from the premarket notification requirements under section
510(k), if the Agency determines that premarket notification is not
necessary to provide reasonable assurance of the safety and
effectiveness of the device. For this device, FDA believes that
premarket notification is necessary to provide reasonable assurance of
safety and effectiveness and, therefore, does not intend to exempt the
device from the premarket notification requirements.
VI. Risks to Health
Although an RIDT is intended for use as an aid in the diagnosis of
influenza infection in conjunction with clinical symptoms and other
laboratory findings, failure of the device to perform as indicated
(producing erroneous or inaccurate results) could mislead the physician
and cause inappropriate or delayed medical treatment of a patient.
Failure of the test to produce accurate test results can also lead to
inaccurate epidemiological information that may contribute to
inappropriate public health responses and to facilitate spread of the
infection in a community. After considering the information discussed
by the Microbiology Devices Panel during the June 13, 2013, meeting in
conjunction with the published literature on the subject and the FDA
Medical Device Reporting system reports, FDA believes the following
risks are associated with RIDTs:
A false negative result may lead to failure to provide a
correct diagnosis and the appropriate treatment of infection caused by
influenza virus and may contribute to unnecessary treatment for another
suspected condition.
A false negative result will also provide incorrect
epidemiological information leading to failure to initiate appropriate
corrective measures to control and prevent additional infections.
A false positive result on the other hand may lead to
delayed treatment of a respiratory infection caused by another
etiologic agent, which could potentially result in a more serious
patient outcome.
A false positive result will also provide incorrect
epidemiological information on the presence of influenza in a
community, which may result in unnecessary patient isolation or contact
limitations and in unnecessary close contact investigations.
A lack of result due to a device malfunction also may lead
to a delayed diagnosis and an inadequate treatment regime and, again,
lead to delayed epidemiological information on the presence of
influenza in a community, contributing to the spread of the infection.
VII. Summary of the Reasons for Reclassification
Due to the mounting evidence and reports from the scientific
community about the poor sensitivity of the RIDTs currently on the
market and the corresponding risks to health associated with low
sensitivity in combination with a rapidly evolving influenza genome
with the potential for a public health emergency, FDA convened a
meeting of the Microbiology Devices Panel of the Medical Devices
Advisory Committee in order to discuss a proposal to reclassify RIDTs
in Sec. 866.3330 from class I to class II with special controls.
Consistent with the opinions expressed by the experts on the panel, FDA
believes that the establishment of special controls, in addition to
general controls, is necessary to mitigate the risks to health not
mitigated by the general controls and provide a reasonable assurance of
safety and effectiveness for these devices. While we believe that
general controls continue to adequately address the risk to health
caused by a lack of result due to a device malfunction we believe
special controls, in addition to general controls, are needed to
control
[[Page 29390]]
the other risks of this device, which are: (1) A false negative result
may lead to failure to provide a correct diagnosis and the appropriate
treatment of infection caused by influenza virus and may contribute to
unnecessary treatment for another suspected condition; (2) a false
negative result will also provide incorrect epidemiological information
leading to failure to initiate appropriate corrective measures to
control and prevent additional infections; (3) a false positive result
on the other hand may lead to delayed treatment of a respiratory
infection caused by another etiologic agent, which could potentially
result in a more serious patient outcome; and (4) a false positive
result will also provide incorrect epidemiological information on the
presence of influenza in a community, which may result in unnecessary
patient isolation or contact limitations and in unnecessary close
contact investigations.
VIII. Special Controls
FDA believes that the following special controls are necessary, in
addition to general controls, to mitigate the risks to health described
in section VI.
1. The device's sensitivity and specificity performance
characteristics must meet one of the following two minimum clinical
performance criteria in order to be cleared for marketing and to remain
on the market:
If the manufacturer chooses to compare the device to viral
culture:
[cir] The sensitivity estimate for the device when testing for
Influenza A must be at least at the 90 percent point estimate with a
lower bound of the 95 percent confidence interval that is greater than
or equal to 80 percent. The sensitivity estimate for the device when
testing for Influenza B must be at least at the 80 percent point
estimate with a lower bound of the 95 percent confidence interval that
is greater than or equal to 70 percent.
[cir] The specificity estimate for the device when testing for
Influenza A and Influenza B must be at least at the 95 percent point
estimate with a lower bound of the 95 percent confidence interval that
is greater than or equal to 90 percent.
If the manufacturer chooses to compare the device to an
appropriate molecular comparator method:
[cir] The positive percent agreement for the device when testing
for Influenza A and Influenza B must be at least at the 80 percent
point estimate with a lower bound of the 95 percent confidence interval
that is greater than or equal to 70 percent.
[cir] The negative percent agreement for the device when testing
for Influenza A and Influenza B must be at least at the 95 percent
point estimate with a lower bound of the 95 percent confidence interval
that is greater than or equal to 90 percent.
2. When performing testing to demonstrate the device meets the
requirements in paragraph 1 of this section, a currently appropriate
and FDA accepted comparator method must be used to establish assay
performance in clinical studies.
3. Annual analytical reactivity testing of the device must be
performed with contemporary influenza strains. This annual analytical
reactivity testing must meet the following criteria:
The appropriate strains to be tested will be identified by
FDA in consultation with CDC and sourced from CDC or a CDC-designated
source. If the annual strains are not available from CDC, FDA will
identify an alternative source for obtaining the requisite strains.
[cir] The testing must be conducted according to a standardized
protocol considered and determined by FDA to be acceptable and
appropriate.
[cir] By July 31 of each calendar year, the results of the last 3
years of annual analytical reactivity testing must be included as part
of the device's labeling. If a device has not been on the market long
enough for 3 years of annual reactivity testing since the device was
given marketing authorization, then the results of every designated
annual reactivity testing since the device was given marketing
authorization by FDA, including the results of annual analytical
reactivity testing performed on the viral strains provided that
calendar year, must be included. The results must be presented as part
of the device's labeling in a tabular format, which includes the
detailed information for each virus tested as described in the
certificate of authentication, either by:
[cir] Placing the results directly in the device's Sec. 809.10(b)
(21 CFR 809.10(b)) compliant labeling in a section of the labeling
devoted to annual analytical reactivity testing; or
[cir] Providing a hyperlink in a section of the device's labeling
to the manufacturer's public Web site where the annual analytical
reactivity testing data can be found. If this option is chosen, the
manufacturer's home page must publicly provide a hyperlink, which can
easily be found and executed, to the annual analytical reactivity
testing results and the Web page containing those annual analytical
reactivity testing results must allow unrestricted viewing access. This
includes being easy to locate the results from the primary part of the
manufacturer's Web site that discusses the device.
4. If an emergency, or a potential emergency, is declared by the
Secretary of Health and Human Services (HHS) for an influenza viral
strain:
Within 30 days from the date that FDA notifies
manufacturers that characterized viral samples are available for test
evaluation, the manufacturer must have testing performed on the device
with that viral strain in accordance with a standardized protocol
considered and determined by FDA to be acceptable and appropriate. The
procedure and location of testing may depend on the nature of the
emerging virus.
Within 60 days from the date that CDC first makes
characterized viral samples available to manufacturers and continuing
until the emergency, or potential emergency, is declared by the
Secretary of HHS to be over, the results of the influenza emergency
analytical reactivity testing, including the detailed information for
the virus tested as described in the certificate of authentication,
must be included as part of the device's labeling in a tabular format,
either by:
[cir] Placing the table directly in the device's Sec. 809.10(b)
compliant labeling in the section of the labeling devoted to annual
analytical reactivity testing and influenza emergency analytical
reactivity testing but separate from the annual analytical reactivity
testing tables; or
[cir] Providing a hyperlink in a section of the device's labeling
devoted to annual analytical reactivity testing and influenza emergency
analytical reactivity testing to a part of the manufacturer's public
Web site where the annual and the emergency analytical reactivity
testing data can be found. If this option is chosen, the manufacturer's
home page must publicly provide a hyperlink, which can easily be found
and executed, to the analytical reactivity and emergency testing
results and the Web page containing those annual analytical reactivity
testing results must allow unrestricted viewing access.
Table 1 shows the special controls set forth in this order that are
needed to address the identified risks for this device not sufficiently
addressed by the general controls to provide a reasonable assurance of
safety and effectiveness of the device.
[[Page 29391]]
Table 1--Identified Risks to Health and Required Mitigation Measures
------------------------------------------------------------------------
Identified risks to health Required mitigation measures
------------------------------------------------------------------------
1. A false negative result may lead Special Controls 1-4.
to failure to provide a correct
diagnosis and the appropriate
treatment of infection caused by
influenza virus and may contribute
to unnecessary treatment for
another suspected condition..
2. A false negative result will Special Controls 1-4.
also provide incorrect
epidemiological information
leading to failure to initiate
appropriate corrective measures to
control and prevent additional
infections..
3. A false positive result on the Special Controls 1-4.
other hand may lead to delayed
treatment of a respiratory
infection caused by another
etiologic agent, which could
potentially result in a more
serious patient outcome..
4. A false positive result will Special Controls 1-4.
also provide incorrect
epidemiological information on the
presence of influenza in a
community, which may result in
unnecessary patient isolation or
contact limitations and in
unnecessary close contact
investigations..
------------------------------------------------------------------------
If this proposed order is finalized, RIDTs in Sec. 866.3330 will
be reclassified into class II with special controls in a new
classification regulation at 21 CFR 866.3328. Adherence to the special
controls, when finalized, in addition to the general controls, is
necessary to provide a reasonable assurance of the safety and
effectiveness of the device.
IX. Environmental Impact
The Agency has determined under 21 CFR 25.34(b) that this action is
of 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.
X. Paperwork Reduction Act of 1995
This proposed administrative order establishes special controls
that refer to previously approved collections of information found in
other FDA regulations. These collections of information 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 part 807, subpart E, regarding premarket notification
submissions have been approved under OMB control number 0910-0120; and
the collections of information in 21 CFR part 801 and 21 CFR 809.10
have been approved under OMB control number 0910-0485.
XI. Proposed Effective Date
FDA proposes that any final order based on this proposed order
become effective 1 year after its date of publication in the Federal
Register.
XII. Comments
Interested persons may submit either electronic comments regarding
this document or the associated Special Controls guideline to http://www.regulations.gov or written comments to the Division of Dockets
Management (see ADDRESSES). 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. 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.
XIII. Reference
The following reference has been placed on display in the Division
of Dockets Management (see ADDRESSES) and may be seen by interested
persons between 9 a.m. and 4 p.m., Monday through Friday, and is
available electronically at http://www.regulations.gov. (FDA has
verified the Web site address in this reference section, but we are not
responsible for any subsequent changes to the Web site after this
document publishes in the Federal Register.)
1. Transcript of FDA's Microbiology Devices Panel Meeting, June 13,
2013. (Available at: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/MicrobiologyDevicesPanel/UCM359554.pdf.)
List of Subjects in 21 CFR Part 866
Biologics, Laboratories, Medical devices.
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, it is
proposed that 21 CFR part 866 be amended as follows:
PART 866--IMMUNOLOGY AND MICROBIOLOGY DEVICES
0
1. The authority citation for part 866 continues to read as follows:
Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 371.
0
2. Add Sec. 866.3328 to subpart D to read as follows:
Sec. 866.3328 Influenza virus antigen detection test system.
(a) Identification. An influenza virus antigen detection test
system is a device intended for the qualitative detection of influenza
viral antigens directly from clinical specimens in patients with signs
and symptoms of respiratory infection. The test aids in the diagnosis
of influenza infection and provides epidemiological information on
influenza. Due to the propensity of the virus to mutate, new strains
emerge over time which may potentially affect the performance of these
devices. Because influenza is highly contagious and may lead to an
acute respiratory tract infection causing severe illness and even
death, the accuracy of these devices has serious public health
implications.
(b) Classification. Class II. The special controls for this device
are:
(1) The device's sensitivity and specificity performance
characteristics must meet one of the following two minimum clinical
performance criteria in order to be cleared for marketing and to remain
on the market:
(i) If the manufacturer chooses to compare the device to viral
culture:
(A) The sensitivity estimate for the device when testing for
Influenza A must be at least at the 90 percent point estimate with a
lower bound of the 95 percent confidence interval that is greater than
or equal to 80 percent. The sensitivity estimate for the device when
testing for Influenza B must be at least at the 80 percent point
estimate with a lower bound of the 95 percent confidence interval that
is greater than or equal to 70 percent.
(B) The specificity estimate for the device when testing for
Influenza A and Influenza B must be at least at the 95 percent point
estimate with a lower bound of the 95 percent confidence interval that
is greater than or equal to 90 percent.
(ii) If the manufacturer chooses to compare the device to an
appropriate molecular comparator method:
[[Page 29392]]
(A) The positive percent agreement for the device when testing for
Influenza A and Influenza B must be at least at the 80 percent point
estimate with a lower bound of the 95 percent confidence interval that
is greater than or equal to 70 percent.
(B) The negative percent agreement estimate for the device when
testing for Influenza A and Influenza B must be at least at the 95
percent point estimate with a lower bound of the 95 percent confidence
interval that is greater than or equal to 90 percent.
(2) When performing testing to demonstrate the device meets the
requirements in paragraph (b)(1) of this section, a currently
appropriate and FDA accepted comparator method must be used to
establish assay performance in clinical studies.
(3) Annual analytical reactivity testing of the device must be
performed with contemporary influenza strains. This annual analytical
reactivity testing must meet the following criteria:
(i) The appropriate strains to be tested will be identified by FDA
in consultation with the Centers for Disease Control and Prevention
(CDC) and sourced from CDC or a CDC-designated source. If the annual
strains are not available from CDC, FDA will identify an alternative
source for obtaining the requisite strains.
(ii) The testing must be conducted according to a standardized
protocol considered and determined by FDA to be acceptable and
appropriate.
(iii) By July 31 of each calendar year, the results of the last 3
years of annual analytical reactivity testing must be included as part
of the device's labeling. If a device has not been on the market long
enough for 3 years of annual reactivity testing since the device was
given marketing authorization, then the results of every designated
annual reactivity testing since the device was given marketing
authorization by FDA, including the results of annual analytical
reactivity testing performed on the viral strains provided that
calendar year, must be included. The results must be presented as part
of the device's labeling in a tabular format, which includes the
detailed information for each virus tested as described in the
certificate of authentication, either by:
(A) Placing the results directly in the device's Sec. 809.10(b) of
this chapter compliant labeling in a section of the labeling devoted to
annual analytical reactivity testing; or
(B) Providing a hyperlink in a section of the device's labeling to
the manufacturer's public Web site where the annual analytical
reactivity testing data can be found. If this option is chosen, the
manufacturer's home page must publicly provide a hyperlink, which can
easily be found and executed, to the annual analytical reactivity
testing results and the Web page containing those annual analytical
reactivity testing results must allow unrestricted viewing access. This
includes being easy to locate the results from the primary part of the
manufacturer's Web site that discusses the device.
(4) If an emergency, or a potential emergency, is declared by the
Secretary of Health and Human Services (HHS) for an influenza viral
strain:
(i) Within 30 days from the date that FDA notifies manufacturers
that characterized viral samples are available for test evaluation, the
manufacturer must have testing performed on the device with that viral
strain according to a standardized protocol considered and determined
by FDA to be acceptable and appropriate. The procedure and location of
testing may depend on the nature of the emerging virus.
(ii) Within 60 days from the date that CDC first makes
characterized viral samples available to manufacturers and continuing
until the emergency, or potential emergency, is declared by the
Secretary of HHS to be over, the results of the influenza emergency
analytical reactivity testing, including the detailed information for
the virus tested as described in the certificate of authentication,
must be included as part of the device's labeling in a tabular format,
either by:
(A) Placing the table directly in the device's Sec. 809.10(b) of
this chapter compliant labeling in the section of the labeling devoted
to annual analytical reactivity testing and influenza emergency
analytical reactivity testing but separate from the annual analytical
reactivity testing tables; or
(B) Providing a hyperlink in a section of the device's labeling
devoted to annual analytical reactivity testing and influenza emergency
analytical reactivity testing to a part of the manufacturer's public
Web site where the annual and the emergency analytical reactivity
testing data can be found. If this option is chosen, the manufacturer's
home page must publicly provide a hyperlink, which can easily be found
and executed, to the analytical reactivity and emergency testing
results and the Web page containing those annual analytical reactivity
testing results must allow unrestricted viewing access.
Dated: May 14, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014-11635 Filed 5-21-14; 8:45 am]
BILLING CODE 4160-01-P