Specific Novel Influenza A Viruses guidance

Guidance for Industry
and FDA Staff
Class II Special Controls
Guidance Document: Reagents
for Detection of Specific Novel
Influenza A Viruses
Document issued on: March 22, 2006
OMB control number: 0910-0584 (expires September 30, 2006). See additional PRA
statement in Section 9 of this guidance.
For questions regarding this document contact Claudia Gaffey at 240-276-0496 x109 or
by email at [email protected], or Roxanne Shively at 240-276-0496 x113, or by
email at [email protected]

U.S. Department of Health and Human Services
Food and Drug Administration
Center for Devices and Radiological Health
Office of In Vitro Diagnostic Device Evaluation and Safety
Division of Microbiology Devices

Contains Nonbinding Recommendations

Preface
Public Comment
Written comments and suggestions may be submitted at any time for Agency
consideration to Division of Dockets Management, Food and Drug Administration, 5630
Fishers Lane, Room 1061, (HFA-305), Rockville, MD, 20852. Alternatively, electronic
comments may be submitted to http://www.fda.gov/dockets/ecomments. Please identify
your comments with the docket number 2006D-0099. Comments may not be acted upon
by the Agency until the document is next revised or updated.

Additional Copies
Additional copies are available from the Internet at:
http://www.fda.gov/cdrh/oivd/guidance/1596.pdf, or to receive this document by your fax
machine, call the CDRH Facts-On-Demand system at 800-899-0381 or 301-827-0111
from a touch-tone telephone. Press 1 to enter the system. At the second voice prompt,
press 1 to order a document. Enter the document number (1596) followed by the pound
sign (#). Follow the remaining voice prompts to complete your request. For questions
regarding the use or interpretation of this guidance contact: Claudia Gaffey at 240-2760496 x109 or by email at [email protected], or Roxanne Shively at 240-2760496 x113, or by email at [email protected]

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Table of Contents
1. Introduction............................................................................................................... 4
2. Background ............................................................................................................... 5
3. Scope......................................................................................................................... 6
4. Risks to Health.......................................................................................................... 6
5. Device Description.................................................................................................... 8
6. Performance ............................................................................................................ 11
7. Labeling .................................................................................................................. 12
8. Postmarket measures............................................................................................... 14
9. Paperwork Reduction Act of 1995......................................................................... 15
References................................................................................................................... 17

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Guidance for Industry and FDA Staff
Class II Special Controls Guidance
Document: Reagents for Detection of
Specific Novel Influenza A Viruses
This guidance represents the Food and Drug Administration's (FDA's) current
thinking on this topic. It does not create or confer any rights for or on any person and
does not operate to bind FDA or the public. You can use an alternative approach if the
approach satisfies the requirements of the applicable statutes and regulations. If you
want to discuss an alternative approach, contact the FDA staff responsible for
implementing this guidance. If you cannot identify the appropriate FDA staff, call the
appropriate number listed on the title page of this guidance.

1. Introduction
This document was developed as a special control to support the classification of reagents
for detection of specific novel influenza A viruses into class II (special controls).
Reagents for detection of specific novel influenza A viruses are devices intended for use
in a nucleic acid amplification test to directly detect specific virus RNA in human
respiratory specimens or viral cultures. Detection of virus RNA aids in the diagnosis of
influenza caused by specific novel influenza A viruses in patients with clinical risk of
infection with these viruses, and also aids in the presumptive laboratory identification of
specific novel influenza A viruses to provide epidemiological information on influenza.
These reagents include primers, probes, and specific influenza A virus controls. They are
used for detecting a specific influenza A virus (for example, a particular subtype or
lineage), as opposed to devices that are used in detecting influenza A virus generally,
without detecting the presence of specific influenza A viruses.
Novel influenza A viruses are new or re-emergent human strains of influenza A that
cause cases or clusters of human disease, as opposed to those human strains commonly
circulating that cause seasonal influenza and to which human populations have residual
or limited immunity (either by vaccination or previous infection).
This guidance is issued in conjunction with a Federal Register notice announcing the
classification of reagents for detection of specific novel influenza A viruses. Any firm
submitting a 510(k) premarket notification for reagents for detection of specific novel
influenza A viruses 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 assurances of safety and

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effectiveness. In addition, the device must satisfy the additional special control specified
in the classification regulation (See Section 3 – Scope).
FDA's guidance documents, including this guidance, do not establish legally enforceable
responsibilities. Instead, guidances describe the Agency's current thinking on a topic and
should be viewed only as recommendations, unless specific regulatory or statutory
requirements are cited. The use of the word should in Agency guidances means that
something is suggested or recommended, but not required.

The Least Burdensome Approach
The issues identified in this guidance document represent those that we believe should be
addressed before your device can be marketed. In developing the guidance, we carefully
considered the relevant statutory criteria for Agency decision-making. We also
considered the burden that may be incurred in your attempt to comply with the guidance
and address the issues we have identified. We believe that we have considered the least
burdensome approach to resolving the issues presented in the guidance document. If,
however, you believe that there is a less burdensome way to address the issues, you
should follow the procedures outlined in the “A Suggested Approach to Resolving Least
Burdensome Issues” document. It is available on our Center web page at:
http://www.fda.gov/cdrh/modact/leastburdensome.html.

2. Background
FDA believes that special controls, when combined with the general controls, will be
sufficient to provide reasonable assurance of the safety and effectiveness of reagents for
detection of specific novel influenza A viruses. A manufacturer who intends to market a
device of this type should (1) conform to the general controls of the Federal Food, Drug
& Cosmetic Act (the Act), including the premarket notification requirements described in
21 CFR 807 Subpart E, (2) address the specific risks to health associated with reagents
for detection of specific novel influenza A viruses identified in this guidance, (3) satisfy
the other special control designated in 21 CFR 866.3332, the classification regulation for
this type of device, and (4) obtain a substantial equivalence determination from FDA
prior to marketing the device.
This guidance document identifies the classification regulation and product code for
reagents for detection of specific novel influenza A viruses. (Refer to Section 3 – Scope).
In addition, other sections of this guidance document list the risks to health identified by
FDA and describe measures that, if followed by manufacturers and combined with the
general controls and other special controls designated for this device type, will generally
address the risks associated with these assays and lead to a timely premarket notification
[510(k)] review and clearance. This document supplements other FDA documents
regarding the specific content requirements of a premarket notification submission. You
should also refer to 21 CFR 807.87 and other FDA documents on this topic, such as
http://www.fda.gov/cdrh/devadvice/314.html.

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3. Scope
The scope of this document is limited to the following devices, described in 21 CFR
866.3332 (product code NXD):
21 CFR 866.3332 - Reagents for detection of specific novel influenza A viruses.
(a) Identification. Reagents for detection of specific novel influenza A viruses are
devices that are intended for use in a nucleic acid amplification test to directly detect
specific virus RNA in human respiratory specimens or viral cultures. Detection of
specific virus RNA aids in the diagnosis of influenza caused by specific novel
influenza A viruses in patients with clinical risk of infection with these viruses, and
also aids in the presumptive laboratory identification of specific novel influenza A
viruses to provide epidemiological information on influenza. These reagents include
primers, probes, and specific influenza A virus controls.
In addition to this guidance document, these devices are subject to a special control
requiring that distribution be limited to laboratories with (i) experienced personnel who
have training in standardized molecular testing procedures and expertise in viral
diagnosis, and (ii) appropriate biosafety equipment and containment. (21 CFR
866.3332(b)(2)).
This special control guidance recommends specific information for mitigating risks
identified in the following section (Section 4 - Risks to Health). It supplements other
applicable guidances. General recommendations for fulfilling premarket notification
(510(k)) requirements, including recommendations on descriptive information,
demonstrating performance, and labeling to establish substantial equivalence are
specified in the document, “Guidance for Industry and FDA Staff: Format for
Traditional and Abbreviated 510(k)s”, issued August 12, 2005. [Ref. 1]. In addition,
FDA has developed draft guidance regarding the type of information generally
recommended for inclusion in a 510(k) for reagents used in nucleic acid amplification
tests. We suggest that manufacturers consult this guidance when final [Ref. 2].

4. Risks to Health
Influenza illness caused by commonly circulating influenza A viruses can have high
morbidity and mortality, particularly in special populations like the elderly and the very
young. Acquired immunity to seasonal influenza viruses is limited because influenza
viruses mutate in small but important ways from year to year (a process known as
antigenic drift). Novel influenza viruses present even greater likelihood of morbidity and
mortality, with the potential to cause widespread disease and/or disease of unusually high
severity, because few people (or none at all) have prior immunologic exposure to surface
glycoproteins of these viruses. In addition, other pathogenicity factors may increase
virulence.

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Failure of reagents for detection of specific novel influenza A viruses to perform as
expected, or failure to interpret results properly may lead to incorrect patient management
decisions and inappropriate public health responses. In the context of individual patient
management, a falsely negative report could lead to delays in providing (or even failure
to provide) definitive diagnosis, appropriate treatment, and infection control and
prevention measures, while a falsely positive report could lead to unnecessary or
inappropriate treatment, or unnecessary control and prevention actions. In the context of
public health, a falsely negative report could lead to a delay in recognition of an outbreak
or cluster of influenza due to a novel influenza A virus, while a falsely positive report
could lead to unnecessary public health actions (e.g., unnecessary or inappropriate
treatment and management of others in the community).
Several factors may negatively affect performance of these reagents, or lead to improper
interpretation of results. First, improper testing and inaccurate reporting may result when
testing is not performed by trained and experienced laboratory personnel. Because use of
these reagents requires specialized techniques, testing by laboratory personnel without
experience and proper training in both preanalytical (specimen processing and extraction)
and analytical molecular procedures increases the risk of obtaining inaccurate results.
Likewise, if laboratory personnel lack expertise in viral diagnosis, there is an increased
risk of providing inadequate or inaccurate interpretation of testing results.
Second, the propensity of all influenza A viruses to mutate (viral RNA changes) may
affect the performance of reagents for detection of specific novel influenza A viruses.
Primers and probes for detection of novel influenza viruses are selected for their
homology with highly conserved regions within viral RNA segments. With continued
mutations over time, annealing of primer and probe reagents with viral targets can
diminish. This may significantly reduce performance of the reagents.
Third, test performance can be affected because the epidemiology and pathology of
disease caused by a specific novel influenza A virus is not fully known. For example,
clinicians and laboratories may not know the optimum types of specimens to collect, and
when during the course of infection these specimens are most likely to contain levels of
virus that can be readily detected.
In addition to the risks that the test will not perform as expected or that results will not be
interpreted properly, testing with these reagents is associated with a potential for
transmission of novel influenza A viruses. Controls that are not adequately inactivated
may themselves be a source of infection. Testing with these devices by inexperienced or
untrained laboratory personnel, as well as use of these reagents in laboratories that do not
have appropriate biosafety equipment and containment procedures, increases risk of
laboratory-acquired infection caused by novel influenza A virus and potential for
spreading infection to others outside the laboratory.
Additionally there is the risk that a novel influenza virus may reassort with other
influenza viruses if not properly contained. Influenza viruses, including novel viruses
such as the H5N1 avian influenza virus, have the capability to reassort with influenza

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viruses circulating in other animal species. Reassortment of a novel influenza A virus
with a human influenza virus, may lead to significant changes in the virus, such as
changes in host range, virulence, and antigenicity, which can lead to the virus acquiring
the ability for sustained person-to-person transmission. This change is believed
necessary to precipitate pandemic influenza. Conditions that favor reassortment are more
likely to occur if testing is done by inexperienced or untrained personnel, or without
appropriate biosafety equipment and containment procedures.
In the table below, FDA has identified the risks to health generally associated with the
use of reagents for detection of specific novel influenza A viruses. Measures
recommended to mitigate these identified risks are given in this guidance document, as
shown in the table below. (In addition, the classification regulation for this type of
device designates an additional special control intended to mitigate these risks, indicating
that distribution of these devices is limited to laboratories with (i) experienced personnel
who have training in standardized molecular testing procedures and expertise in viral
diagnosis, and (ii) appropriate biosafety equipment and containment. See 21 CFR
866.3332(b)(2).)
We recommend that you conduct a risk analysis, prior to submitting your premarket
notification, to identify any other risks specific to your device. The premarket
notification should describe the risk analysis method. If you elect to use an alternative
approach to address a particular risk identified in this document, or have identified risks
additional to those in this document, you should provide sufficient detail to support the
approach you have used to address that risk.
Identified risk
Failure of testing to perform properly
a. Failure of the reagents to perform as
expected, including inability to detect
mutated viral RNA
b. Inability to optimize testing when
epidemiology or pathology of viral/host
factors is not fully understood

Recommended
mitigation measures

Sections 5-8

Failure to properly interpret test results

Sections 5-8

Laboratory-acquired infection and reassortment

Sections 5 and 7

5. Device Description
Intended Use

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Your 510(k) must include labeling that describes the intended use of your product. (See
21 CFR 807.87(e)). You should ensure that all elements of the intended use are clearly
stated, particularly regarding the specific viruses the device is intended to detect (for
example, influenza A/H5 (Asian lineage)). The intended use includes the viral RNA
region detected (analyte), the patient population to be tested, specimen types for which
testing will be indicated, and any specific conditions of use.
In your 510(k), you should clearly describe the following information related to the
intended use of your product:
•

The identity, phylogenetic relationship, or other recognized characterization of a
specific novel influenza virus that your device is designed to detect.

•

How the device test results will be used in a diagnostic algorithm and other
measures that would be needed for a definitive laboratory identification of a
specific novel influenza A virus.

•

Clinical and epidemiological parameters that are relevant to a patient case
diagnosis. The World Health Organization (WHO) and other public health
entities provide criteria that may be used as a guide for defining patient cases.

Note: Recognized laboratory methods for definitive identification of certain novel
influenza viruses are available (e.g., WHO Manual on Animal Influenza Diagnosis and
Surveillance) [Ref. 3.]; sequencing of DNAs generated by subtype-specific primers may
also be used to definitively identify a specific novel influenza virus [Ref. 4].
Reagents and other device components
When describing reagents and other device components in your 510(k), we recommend
you follow general guidance provided in other FDA guidance documents. FDA has
developed draft guidance regarding Nucleic Acid Amplification Testing, which will be
particularly relevant when final [Ref. 2]. Additionally, for reagents for detection of
specific novel influenza A viruses, you should describe design requirements for your
device that address or mitigate risks associated with primers, probes, and controls used in
a nucleic-acid based test procedure to detect viral RNA segments from a specific novel
influenza A virus. Examples include:
•

Designing your reagent for use in a closed tube test system, to minimize false
positives due to contamination or carryover.

•

Providing multiple probes that enable detection of virus variants appearing due to
mutations within the target RNA segment(s), or variants within a designated novel
influenza virus strain (or lineage).

•

Developing a positive virus control that minimizes the risk that the control itself
will be a source of infection or of reassortment with other influenza A viruses
handled or maintained in the type of clinical laboratory where testing is intended
to be done.

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•

Developing methods for extraction and purification that yield suitable quality and
quantity of viral RNA from different specimen types for use in the test system
with your reagents.

•

Optimizing your reagents and test procedure for recommended instruments.

We expect that appropriate literature references will not likely be available to detail
reliable RNA targets within any viral RNA region (e.g., H0 within the hemagglutinin
RNA) characteristic for a specific novel influenza A virus. In your 510(k), you should
provide performance information that supports the conclusion that your design
requirements have been met. You should also provide information to verify the design of
your reagents (e.g., rationale for selection of specific conserved target sequences and the
methods used to design primers and probes). (See Section 6 – Performance).
You should assure acceptable reproducibility and efficiency of the recommended
extraction procedure(s) from respiratory specimen types you recommend for testing (e.g.,
swabs, aspirates, and viral culture media).
Testing Procedures using your device
In your 510(k), you should describe, in detail, the principles of operation applicable to
your device in detecting and differentiating a specific novel influenza A virus. For
reagents for detection of specific novel influenza A viruses, you should specifically
describe testing conditions, procedures and controls designed to provide safeguards for
conditions that can cause false positive and false negative results, or present a biosafety
hazard. These include, but are not limited to:
•

Overall design of the testing procedure, including control elements incorporated
into the recommended testing procedures. These controls should approximate the
lower range of clinically relevant viral RNA levels and should be extracted as a
clinical sample.

•

Recommendations for additional controls that monitor for contamination and
extraction efficiency (e.g., a blank extracted with each specimen test, and
concurrent amplification of an endogenous human gene in the sample, as a control
for nucleic acid extraction and inhibition).

•

Features and additional controls that reduce failure to recognize procedural errors
or factors (e.g., degradation of master mix) that adversely affect amplification and
detection conditions.

•

Biological Safety Level (BSL) under which testing procedures should be
performed.

We recommend that you include a description of all additional procedures, methods, and
practices incorporated into your directions for use (See Section 7 - Labeling) that mitigate
risks associated with testing for a specific novel influenza A virus.

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Interpreting Test Results/Reporting
In your 510(k), you should describe how presumptive positive, equivocal, and negative
results are determined and how they should be interpreted. There should be clear
explanations for how interpretative algorithms have been determined. In addition, please
see Section 8 (Postmarket Measures) for monitoring results over time to identify changes
in performance due to biological changes with the virus, or changes in performance when
prevalence changes from the existing prevalence at the time your product is evaluated.

6. Performance
In your 510(k), you should provide descriptive information on the studies done to support
performance of your reagents for detection of specific novel influenza A viruses. FDA
has developed draft guidance elsewhere making general recommendations for this
information [Ref. 2].
Your 510(k) should include performance information demonstrating:
•

Detection of a specific novel influenza A virus (e.g., influenza A/H5 (Asian
lineage)) directly in respiratory specimens from patients who were identified
clinically and epidemiologically, and were laboratory confirmed patient cases
(using WHO recommended criteria) [Ref. 3].

•

Low likelihood of presumed false positive results when testing specimens from
patients who were known to have other influenza A or influenza B virus
infections, or who have no influenza viruses detected by WHO-recommended
methods (primarily virus culture) [Ref. 4].

•

Detection of known variant novel influenza A viruses (e.g., clades, lineages).

•

Lack of cross-reactivity with other broadly representative influenza A viruses that
are known to cause human infections (e.g., influenza A/H3N2), with other
respiratory viruses (e.g., respiratory syncytial virus, human metapneumovirus,
etc.) and with relevant bacterial species (e.g., Streptococcus pneumoniae,
Staphylococcus aureus).

•

Rare unexpected positivity when testing is done on a large group of specimens
from individuals with respiratory symptoms, and from viral cultures.

•

Reproducible and efficient extraction procedure(s) for respiratory specimen types
that you recommend for testing (e.g., swabs, aspirates, and viral culture media).

•

Reproducible results without unexpected false positive or false negative test
results in multiple clinical laboratories. Samples should include those
representing the lower end of the viral level range that is clinically relevant (e.g.,
101-106 TCID50/mL viral levels have been documented in respiratory specimens
from patients with influenza A/H5 infections; thus samples should represent that
lower range for A/H5 viruses).

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Clinical studies
FDA recommends that you assess the ability of your device to detect the specific novel
influenza A virus in specimens from patients who are case-confirmed, in accordance with
WHO criteria for laboratory-confirmed cases. Fresh samples are preferred and testing
multiple specimen types is helpful for positive case determinations. Any additional
testing that is done to qualify presumptive positives and equivocal test results should
include WHO-recommended methods for characterizing and identifying a novel
influenza A virus, including sequencing as needed.
When evaluating your device with specimens from patients not suspected to have a novel
influenza virus infection, fresh samples are preferred. However, archived samples may
be useful to expand representation of specimens (e.g., geographically diverse, different
specimen types recommended). Archived samples may be useful to provide the variety
of specimen types from patients who have other respiratory infections, and from whom
fresh specimens may not be readily available (e.g., S-coronavirus positive samples).

7. Labeling
IVD devices for direct detection of specific novel influenza A viruses in human
specimens, like other devices, are subject to statutory requirements for labeling (Federal
Food, Drug and Cosmetic Act (the Act), Sections 502(a), 201(n); 21 USC §§ 352(a),
321(n)). Reagents for detection of specific novel influenza A viruses must provide
adequate directions for use and adequate warnings and precautions. (Section 502(f); 21
USC § 352(f)). Specific labeling requirements for all IVD devices are set forth in 21
CFR 809.10.
Although final labeling is not required for 510(k) clearance, final labeling for in vitro
diagnostic devices must comply with the requirements of 21 CFR 809.10 before an in
vitro diagnostic device is introduced into interstate commerce.
To ensure compliance with section 502 of the Act and 21 CFR 809.10, FDA recommends
that labeling for these devices (reagents for detection of specific novel influenza A
viruses) address the items identified below. These labeling recommendations also help to
mitigate the risks identified previously in this guidance to ensure safe and effective use of
these devices, particularly when a novel influenza A virus may be emerging.
Your labeling should clearly describe the identity, phylogenetic relationship, or other
recognized characterization of a specific novel influenza virus that your device is
designed to detect, and the associated clinical aspects of human infection.
Your labeling should also include a statement such as the following: “If infection with a
novel influenza A virus is suspected based on current clinical and epidemiological
screening criteria recommended by public health authorities, specimens should be
collected with appropriate infection control precautions for novel virulent influenza

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viruses. Viral culture should not be attempted in these cases unless a BSL 3+ facility is
available to receive and culture specimens.”
Intended Use
In addition to specific elements that describe the analyte detected, your intended usei
should specify indications for testing respiratory specimens from patients with symptoms
of respiratory illness and a risk of exposure, and that these reagents should be used in
conjunction with other laboratory testing and clinical observations. FDA also
recommends that your statement of intended use be clarified by a warning statement such
as: “Negative results do not preclude influenza virus infection and should not be used as
the sole basis for treatment or other patient management decisions.”
You should also prominently provide the following statement immediately below your
intended use: “For use by experienced personnel who have training in standardized
molecular testing procedures and expertise in viral diagnosis, in laboratories with
appropriate biosafety equipment and containment procedures.”
Directions for use
You should provide clear and concise instructions that delineate the clinical and
epidemiological relevance of the particular novel influenza strain that is detected,
technological features of the specific device, procedures for using reagents, and types of
controls that will minimize risks of inaccurate results. Instructions should encourage use
of additional control measures and testing of control material to ensure use in a safe and
effective manner.
If your reagents will not include reagents for extraction and preparation, you should
provide specifications for the extraction and preparation reagents that users will need to
perform testing. You should also provide specifications for assessing the quality of
extracted/purified samples.
Quality Control
We recommend that you provide a description of quality control recommendations, types
of procedures and material that can be used as additional quality control measures, and
the expected results for acceptability of control testing.
Precautions for interpretation
We recommend that you incorporate directions for reporting results into the Results
section,ii including a reminder to report results to state or local public health departments.

i
ii

21 CFR 809.10(a)(2); 21 CFR 809.10(b)(2).
21 CFR 809.10(b)(9).
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Additionally you should provide the following types of statements in the Limitationsiii
section:
•

Negative results (e.g., no novel viral RNA detected) do not exclude influenza
infection with other influenza A or B viruses.

•

Additional testing for influenza A or B, or other respiratory infections may be
required.

•

Results that are positive for a novel influenza A virus do not definitively identify
a specific influenza A virus subtype.

•

Optimum specimen types and timing for peak viral levels during infections
caused by a novel influenza A virus have not been determined. Collection of
multiple specimens from the same patient may be necessary to detect the virus.

•

False negative results may occur if a specimen is improperly collected,
transported or handled. False negative results may occur if inadequate numbers
of organisms are present in the specimen.

•

Positive and negative predictive values are highly dependent on prevalence. False
positive test results are likely when prevalence of disease due to a novel influenza
A virus is low or non-existent in a community.

•

If the virus mutates in the target region, a specific novel influenza A virus may
not be detected or may be detected less predictably.

•

Inhibitors or other types of interference may produce a false negative result.

Performance Characteristicsiv
We recommend that in your labeling, you describe the population(s) (i.e., geographical
location, specimen types, and age groups) whose specimens were tested to support
performance characteristics. You should separately represent testing done on specimens
from patient cases that are laboratory-confirmed with influenza due to the novel influenza
A virus that your device is intended to detect.
You should include a description of the design and evaluation of results for all studies
that would aid users in interpreting test results.

8. Postmarket measures
We recommend that you obtain and analyze data postmarket to ensure the continued
reliability of your device in detecting the specific novel influenza A virus that it is
intended to detect, particularly given the propensity for influenza viruses to mutate and

iii
iv

21 CFR 809.10(b)(10).
21 CFR 809.10(b)(12).
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the potential for changes in disease prevalence over time. We recommend the following
measures:
•

As updated influenza viral sequences become available (from WHO, NIH and
other public health entities), you should compare them with your primer/probe
sequences and incorporate the result of these analyses into your Quality
Management System, as required by 21 CFR 820.100(a)(1), Corrective and
Preventive Action. Further, these analyses should be evaluated against the device
design validation and risk analysis required by 21 CFR 820.30(g), Design
Validation, to determine if any design changes may be necessary.

•

If the prevalence of influenza caused by the specific novel influenza A virus that
your device is intended to detect changes, compared to the prevalence existing
when the clinical evaluation(s) described in your 510(k) were conducted, you
should collect data on the clinical performance of your device under the new
prevalence conditions. The prevalence of infection with the specific novel
influenza virus that your device is intended to detect may change significantly
with time, possibly affecting your device performance. The labeling of your
device may need to be revised to reflect the new clinical performance data.

To demonstrate how you will address this aspect of the special control, we recommend
that you provide a plan that describes how you intend to address the postmarket elements
described above with your 510(k) submission. FDA will evaluate whether this plan will
help to mitigate the risks presented by the device and therefore help to provide continued
reasonable assurance of the safety and effectiveness of the device.

9. Paperwork Reduction Act of 1995
This 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 time required to complete this information collection is estimated to average 10
hours per response, including the time to review instructions, search existing data
resources, gather the data needed, and complete and review the information collection.
Send comments regarding this burden estimate or suggestions for reducing this burden to:
Denver Presley, Office of Information Resources Management (HFA-250), Food and
Drug Administration, 5600 Fishers Lane, Room 16B-26; Rockville, MD 20857, 301-8271472.
This guidance also refers to previously approved collections of information found in 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 21 CFR § 809 have been approved under
OMB Control No. 0910-0485; the collections of information in 21 CFR § 807 have been

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approved under OMB Control No. 0910-0120; the collections of information in 21 CFR §
820 have been approved under OMB Control No. 0910-0073.

An agency may not conduct or sponsor, and a person is not required to respond to, a collection of
information unless it displays a currently valid OMB control number. The OMB control number
for this information collection is 0910-0584 (expires September 30, 2006).

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References
[1] Guidance for Industry and FDA Staff: Format for Traditional and Abbreviated
510(k)s, issued August 12, 2005. Available at
http://www.fda.gov/cdrh/ode/guidance/1567.html
[2] Nucleic Acid Based In Vitro Diagnostic Devices for Detection of Microbial
Pathogens - Draft Guidance for Industry and FDA Staff, DRAFT GUIDANCE, issued
on: December 8, 2005; available at http://www.fda.gov/cdrh/oivd/guidance/1560.html
[3] WHO (2002). WHO manual on animal influenza diagnosis and surveillance, 2002,
Geneva, World Health Organization (document WHO/CDS/CSR/NCS/2002.5, available
at:
http://www.who.int/csr/resources/publications/influenza/en/whocdscsrncs20025rev.pdf
[4] WHO (2005). Recommended laboratory tests to identify avian influenza A virus in
specimens from humans, 2005, Geneva, World Health Organization, available at
http://www.who.int/csr/disease/avian_influenza/guidelines/labtests/en/index.html

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