(125 days)
Not Found
No
The device description and performance studies focus on standard molecular diagnostic techniques (RT-PCR) and do not mention any AI or ML components for data analysis or interpretation.
No.
The device is used for in vitro qualitative detection and differentiation of specific influenza viral RNA, which is a diagnostic purpose, not a therapeutic one.
Yes
The "Intended Use / Indications for Use" section explicitly states that the assay is for "in vitro qualitative detection and differentiation of influenza A and 2009 H1N1 influenza viral RNA... from human patients with signs and symptoms of respiratory infection in conjunction with clinical and epidemiological risk factors." This directly describes a diagnostic purpose.
No
The device is described as a "Microfluidic Molecular System" which includes a test kit (reagents and consumables), an instrument (3M Integrated Cycler), and software (Integrated Cycler Studio Software). While software is a component, it is not the sole component of the medical device.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states that the assay is intended for "in vitro qualitative detection and differentiation of influenza A and 2009 H1N1 influenza viral RNA... from human patients". The term "in vitro" is a key indicator of an IVD, meaning it's used outside of the body, typically in a laboratory setting, to examine samples.
- Device Description: The description details a "nucleic acid amplification test" that uses "real-time reverse transcriptase polymerase chain reaction (RT-PCR)" to detect viral RNA in biological samples (swabs and aspirates). This is a common methodology for IVD tests that analyze biological specimens to diagnose or detect diseases.
- Sample Type: The device is designed to test "nasopharyngeal swabs (NPS), nasal swabs (NS), and nasopharyngeal aspirates (NPA) from human patients". These are biological samples collected from individuals for diagnostic purposes.
- Purpose: The purpose is to aid in the diagnosis of influenza A and 2009 H1N1 influenza in patients with respiratory symptoms. This aligns with the definition of an IVD, which is used to provide information for diagnosis, monitoring, or treatment decisions.
- Performance Studies: The document includes detailed performance studies (Clinical Agreement, Reproducibility, Limit of Detection, Analytical Reactivity, Cross-Reactivity, Interference) which are standard for demonstrating the analytical and clinical validity of an IVD.
- Predicate Devices: The mention of predicate devices (other IVDs) further confirms that this device falls within the category of IVDs.
Therefore, based on the provided information, the Focus Diagnostics Simplexa™ Influenza A H1N1 (2009) assay is clearly an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The Focus Diagnostics Simplexa™ Influenza A H1N1 (2009) assay is intended for use on the 3M Integrated Cycler as part of the Microfluidic Molecular System for the in vitro qualitative detection and differentiation of influenza A and 2009 H1N1 influenza viral RNA in nasopharyngeal swabs (NS), and nasopharyngeal aspirates (NPA) from human patients with signs and symptoms of respiratory in conjunction with clinical and epidemiological risk factors.
Negative results do not preclude influenza virus infection and should not be used as the sole basis for treatment or other patient management decisions.
Performance characteristics for influenza A were established during the 2009-2010 influenza season when 2009 H1N1 influenza was the predominant influenza A virus in circulation. When other Influenza A viruses are emerging, performance characteristics may vary.
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 viruses and sent to state or local health department for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.
Product codes (comma separated list FDA assigned to the subject device)
OOW
Device Description
Simplexa™ Influenza A H1N1 (2009) test kit is a nucleic acid amplification test that uses real-time reverse transcriptase polymerase chain reaction (RT-PCR) amplification to enable simultaneous and distinct detection of influenza A and 2009 H1N1 influenza in a single reaction from nasophayngeal swabs (NPS), nasal swabs (NS), and nasopharyngeal aspirates (NPA). The assay combines real-time PCR amplification with fluorescent signal detection technology. A bi-functional fluorescent probe-primer is used together with a reverse primer to amplify a specific target (for each analyte and internal control). A fluorescent signal is generated after the separation of the fluorophore from the quencher as a result of the binding of a probe element to the extended RNA fragment synthesized during amplification.
The 3M Integrated Cycler is a rapid real-time Polymerase Chain Reaction thermocycler used for the identification of nucleic acid from prepared biological samples. The instrument utilizes disk media to contain and to process samples. The instrument uses real time flourometric detection to identify targets within the sample wells. The instrument is controlled by an external computer running the Integrated Cycler Studio Software. Together, the instrument, software and test kit are referred to as the "Microfluidic Molecular System."
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
nasopharyngeal swabs (NS), and nasopharyngeal aspirates (NPA), nasophayngeal swabs (NPS), nasal swabs (NS)
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Specimens were prospectively collected at three sites from patients with signs and symptoms of influenza like illness (Austin, TX (September 2009) and the New South Wales region of Australia (July - September 2009). Specimens were blinded and randomly distributed to 3 U.S. clinical laboratories for testing. Specimens were determined to be positive for 2009 H1N1 influenza by a composite reference method including the Luminex xTAG RVP Flu A target, a validated PCR assay using primer and probe sequences published by the CDC and a well characterized PCR followed by sequencing. Two results were generated for each specimen, an influenza A result and a 2009 H1N1 influenza sub-typing result. Both results must be positive to determine that a specimen is 2009 H1N1 influenza positive.
299 prospectively collected nasal/nasopharyngeal swabs and 112 nasopharyngeal aspirates were analyzed using the Simplexa™ Influenza A H1N1 (2009) assay. The data presented below are stratified by both result and specimen type. Fifteen (15) specimens (10 swabs and 5 aspirates) were excluded from the analysis because there was no consensus among the reference assays for the influenza A result. Twelve (12) specimens (9 swabs and 3 aspirates) were excluded from the 2009 H1N1 Influenza Clinical Acreement Summary tables as sequencing data used to determine subtype was not available. These 12 specimens are included in the Influenza A Clinical Agreement Summary tables.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Reproducibility: Three investigative sites assessed the device's inter-laboratory reproducibility and inter/intra-assay reproducibility. Each of the three laboratories tested eighteen samples, the Positive Control and the No Template Control, in triplicate on five different days. Each site had two operators who each ran the assay once per day, for a total of two runs per day. Two sites performed the extraction using the MagNA Pure LC Total Nucleic Acid Isolation Kit; one site performed the extraction step using the Qiagen QlAamp Viral RNA Mini Kit.
FLUA Inter-Assay Total %CV range 0.0 to 4.8
FLUA Intra-Assay Total %CV range 0.0 to 6.6
H1N1 Inter-Assay Total %CV range 0.0 to 1.8
H1N1 Intra-Assay Total %CV range 0.0 to 4.7
Limit of Detection:
Simplexa™ Influenza A H1N1 (2009) Limit of Detection - FLUA: LoD MagNA Pure extraction (TCID50/mL) for Swab and Aspirate samples and LoD QIAgen extraction (TCID50/mL) for Swab and Aspirate samples for various Influenza A Strains (A/California/7/2009 NYMC x-179-A, A/Swine NY/02/2009 H1N1, A/Solomon Island/03/06 H1, A/Brisbane/59/07 H1, A/Brisbane/10/07 H3, A/Wisconsin/67/05 H3). The LoD values ranged from 1x10-1 to 2.7x101 TCID50/mL.
Simplexa™ Influenza A H1N1 (2009) Limit of Detection - H1N1: LoD MagNA Pure extraction (TCID50/mL) for Swab and Aspirate samples and LoD QIAgen extraction (TCID50/mL) for Swab and Aspirate samples for 2009 Influenza A Strains (A/California/7/2009 NYMC x-179-A, A/Swine NY/02/2009 H1N1). The LoD values ranged from 1x10^1 to 2.7x10^1 TCID50/mL.
Analytical Reactivity:
Estimated LoD for Influenza A Strains (A/PR/8/34 H1N1, A/New Caledonia/20/99 H1N1, A/Taiwan/42/06 H1N1, A/WS/33 H1N1, A/Hong Kong/8/68 H3N2) was 1x10^0.
Cross-Reactivity: No cross reactivity was detected for either Influenza A or 2009 H1N1 to organisms that are closely related to influenza A or 2009 H1N1, or cause similar clinical symptoms as influenza A or 2009 H1N1, or present as normal flora in the specimen types of interest.
Interference: Potentially interfering substances were not tested with this methodology; common medications taken by study participants do not appear to inhibit the PCR process.
Clinical Agreement:
2009 H1N1 Influenza Clinical Agreement Summary - Prospectively Collected Swabs:
N=280. Positive Agreement: 100% (101/101), 95% CI:96.3-100%. Negative Agreement: 95.5% (171/179), 95% CI:91.4-97.7%.
2009 H1N1 Influenza Clinical Agreement Summary - Prospectively Collected Aspirates:
N=104. Positive Agreement: 100% (24/24), 95% CI:86.2-100%. Negative Agreement: 92.5% (74/80), 95% CI:84.6-96.5%.
Influenza A Clinical Agreement Summary - Prospectively Collected Swabs:
N=289. Positive Agreement: 100% (116/116), 95% CI:96.8-100%. Negative Agreement: 92.5% (160/173), 95% CI:87.6-95.6%.
Influenza A Clinical Agreement Summary - Prospectively Collected Aspirates:
N=107. Positive Agreement: 100% (31/31), 95% CI:89-100%. Negative Agreement: 96.1% (73/76), 95% CI:89-98.6%.
2009 H1N1 Influenza Clinical Agreement Summary - Retrospectively Collected Swabs:
N=210. Positive Agreement: 100% (57/57), 95% CI:93.7-100%. Negative Agreement: 90.8% (139/153), 95% CI:85.2-94.5%.
Influenza A Clinical Agreement Summary - Retrospectively Collected Swabs:
N=211. Positive Agreement: 99.2% (131/132), 95% CI:95.8-99.9%. Negative Agreement: 83.5% (66/79), 95% CI:73.9-90.1%.
Two retrospectively collected washes were found to be positive for 2009 H1N1 influenza by the composite reference method and by the Simplexa assay.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
2009 H1N1 Influenza Clinical Agreement Summary - Prospectively Collected Swabs:
% Positive Agreement 100%(101/101) 95% CI:96.3-100%
% Negative Agreement 95.5%(171/179) 95% CI:91.4-97.7%
2009 H1N1 Influenza Clinical Agreement Summary - Prospectively Collected Aspirates:
% Positive Agreement 100%(24/24) 95% CI:86.2-100%
% Negative Agreement 92.5%(74/80) 95% CI:84.6-96.5%
Influenza A Clinical Agreement Summary - Prospectively Collected Swabs:
% Positive Agreement 100%(116/116) 95% CI:96.8-100%
% Negative Agreement 92.5%(160/173) 95% CI:87.6-95.6%
Influenza A Clinical Agreement Summary - Prospectively Collected Aspirates:
% Positive Agreement 100%(31/31) 95% CI:89-100%
% Negative Agreement 96.1%(73/76) 95% CI:89-98.6%
2009 H1N1 Influenza Clinical Agreement Summary - Retrospectively Collected Swabs:
% Positive Agreement 100%(57/57) 95% CI:93.7-100%
% Negative Agreement 90.8%(139/153) 95% CI:85.2-94.5%
Influenza A Clinical Agreement Summary - Retrospectively Collected Swabs:
% Positive Agreement 99.2%(131/132) 95% CI:95.8-99.9%
% Negative Agreement 83.5%(66/79) 95% CI:73.9-90.1%
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
K091667, K081483, K063765, K080570
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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.(b)
Classification. Class II (special controls). The special controls are:(1) FDA's guidance document entitled “Class II Special Controls Guidance Document: Reagents for Detection of Specific Novel Influenza A Viruses.” See § 866.1(e) for information on obtaining this document.
(2) The distribution of these devices is limited to laboratories with experienced personnel who have training in standardized molecular testing procedures and expertise in viral diagnosis, and appropriate biosafety equipment and containment.
0
Image /page/0/Picture/0 description: The image shows the logo for Focus Diagnostics. The logo consists of the word "FOCUS" in large, bold, sans-serif font, with the word "Diagnostics" in a smaller font size underneath. A curved, black shape is positioned to the left of the word "FOCUS", adding a visual element to the logo.
510(k) Summary of Safety and Effectiveness
Simplexa™ Influenza A H1N1 (2009) Catalog No. MOL2500 Prepared Date: May 18, 2010 Page 1 of 9
| Applicant | Focus Diagnostics, Inc.
11331 Valley View Street
Cypress, California 90630
USA | |
|--------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------|
| Establishment Registration No. | 2023365 | |
| Contact Person | Tara Viviani
tel 714.822.2115
fax 714.822.3898
tviviani@focusdx.com | MAY 24 2010 |
| Summary Date | May 18, 2010 | |
| Proprietary Name | Simplexa™ Influenza A H1N1 (2009) | |
| Generic Name | Influenza A H1N1 2009 Real Time RT-PCR | |
| Classification | Class II, Special Controls
Luminex Diagnostics XTAG RESPIRATORY VIRAL PANEL
(K091667, K081483, K063765)
CDC Human Influenza Virus Real-Time RT- PCR Detection and
Characterization Panel (K080570) | |
Intended Use
The Focus Diagnostics Simplexa™ Influenza A H1N1 (2009) assay is intended for use on the 3M Integrated Cycler as part of the Microfluidic Molecular System for the in vitro qualitative detection and differentiation of influenza A and 2009 H1N1 influenza viral RNA in nasopharyngeal swabs (NS), and nasopharyngeal aspirates (NPA) from human patients with signs and symptoms of respiratory in conjunction with clinical and epidemiological risk factors.
Neqative results do not preclude influenza virus infection and should not be used as the sole basis for treatment or other patient management decisions.
Performance characteristics for influenza A were established during the 2009-2010 influenza season when 2009 H1N1 influenza was the predominant influenza A virus in circulation. When other Influenza A viruses are emerging, performance characteristics may vary.
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 viruses and sent to state or local health department for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.
Device Description
Simplexa™ Influenza A H1N1 (2009) test kit is a nucleic acid amplification test that uses real-time reverse transcriptase polymerase chain reaction (RT-PCR) amplification to enable simultaneous and distinct detection of influenza A and 2009 H1N1 influenza in a single reaction from nasophayngeal swabs (NPS), nasal swabs (NS), and nasopharyngeal aspirates (NPA). The assay combines real-time PCR amplification with fluorescent signal detection technology. A bi-functional fluorescent probe-primer is used together with a reverse primer to amplify a specific target (for each analyte and internal control). A fluorescent signal is generated after the separation of the fluorophore from the quencher as a result of the binding of a probe element to the extended RNA fragment synthesized during amplification.
The 3M Integrated Cycler is a rapid real-time Polymerase Chain Reaction thermocycler used for the identification of nucleic acid from prepared biological samples. The instrument utilizes disk media to contain and to process samples. The instrument uses real time flourometric detection to identify targets within the sample wells. The instrument is controlled by an external computer running the Integrated Cycler Studio Software. Together, the instrument, software and test kit are referred to as the "Microfluidic Molecular System."
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Image /page/1/Picture/0 description: The image shows the logo for Focus Diagnostics. The logo features a stylized, curved shape resembling a crescent or a checkmark above the word "FOCUS" in bold, sans-serif font. Below "FOCUS" is the word "Diagnostics" in a smaller, sans-serif font, underlined with a thin line.
510(k) Summary of Safety and Effectiveness Simplexa™ Influenza A H1N1 (2009) Catalog No. MOL2500 Prepared Date: May 18, 2010 Page 2 of 9
Predicate Device Information
| Trade Name / Method | 510(k)
submitter | 510(k)
number | Decision Date | Panel | Product
Code(s) |
|-------------------------------------------------------------------------------------------|-----------------------------------------------------|-------------------------------|----------------------------------------|----------------------|-----------------------|
| XTAG Respiratory
Viral Panel - FluA | Luminex | K091667
K081483
K063765 | 06/25/2009
06/25/2008
11/30/2007 | Microbiology
(83) | OCC, OEM,
OEP |
| CDC Human Influenza
Virus Real-Time RT-
PCR Detection and
Characterization Panel | Centers for
Disease
Control and
Prevention | K080570 | 09/30/2008 | Microbiology
(83) | NXD, OEP,
OCC, NSU |
| Item
| Name | Device | Predicate | |
|---|---|---|---|
| Simplexa™ Influenza A | |||
| H1N1 (2009) | xTAG Respiratory Viral | ||
| Panel - FLUA | CDC Human Influenza | ||
| Virus Real-Time RT-PCR | |||
| Detection and | |||
| Characterization Panel | |||
| Intended Use | The Focus Diagnostics | ||
| Simplexa™ Influenza A H1N1 | |||
| (2009) assay is intended for | |||
| use on the 3M Integrated | |||
| Cycler as part of the | |||
| Microfluidic Molecular System | |||
| for the in vitro qualitative | |||
| detection and differentiation of | |||
| influenza A and 2009 H1N1 | |||
| influenza viral RNA in | |||
| nasopharyngeal swabs (NPS), | |||
| nasal swabs (NS), and | |||
| nasopharyngeal aspirates | |||
| (NPA) from human patients | |||
| with signs and symptoms of | |||
| respiratory infection in | |||
| conjunction with clinical and | |||
| epidemiological risk factors. |
Negative results do not
preclude influenza virus
infection and should not be
used as the sole basis for
treatment or other patient
management decisions.
Performance characteristics
for influenza A were
established during the 2009-
2010 influenza season when
2009 H1N1 influenza was the
predominant influenza A
viruses in circulation. When
other Influenza A viruses are
emerging, performance
characteristics may vary.
If infection with a novel
Influenza A virus is suspected | The xTAG® Respiratory
Viral Panel (RVP) is a
qualitative nucleic acid
multiplex test intended for
the simultaneous detection
and identification of
multiple respiratory virus
nucleic acids in
nasopharyngeal swabs
from individuals suspected
of respiratory tract
infections. The following
virus types and subtypes
are identified using RVP:
Influenza A, Influenza A
subtype H1, Influenza A
subtype H3, Influenza B,
Respiratory Syncytial Virus
subtype A, Respiratory
Syncytial Virus subtype B,
Parainfluenza 1,
Parainfluenza 2, and
Parainfluenza 3 virus,
Human Metapneumovirus,
Rhinovirus, and
Adenovirus. The detection
and identification of specific
viral nucleic acids from
individuals exhibiting signs
and symptoms of
respiratory infection aids in
the diagnosis of respiratory
viral infection if used in
conjunction with other | The Human Influenza Virus
Real-time RT-PCR
Detection and
Characterization Panel
(rRT-PCR Flu Panel) is
intended for use in Real-
time RT-PCR assays on an
ABI 7500 Fast Dx Real-
time PCR instrument in
conjunction with clinical
and epidemiological
information:
- for qualitative detection
of influenza virus type A or
B in symptomatic patients
from viral RNA in
nasopharyngeal and/or
nasal swab specimens, *
for determination of the
subtype of seasonal human
influenza A virus, as
seasonal A/HI or A/H3, if
present, from viral RNA in
nasopharyngeal and/or
nasal swab specimens, - for presumptive
identification of virus in
patients who may be
infected with influenza A
subtype A/H5 (Asian
lineage) from viral RNA in
human respiratory
specimens and viral culture
in conjunction with clinical |
| Item
Name | Device | Predicate | |
| | Simplexa™ Influenza A
H1N1 (2009) | xTAG Respiratory Viral
Panel - FLUA | CDC Human Influenza
Virus Real-Time RT- PCR
Detection and
Characterization Panel |
| | 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 viruses and
sent to state or local health
department for testing. Viral
culture should not be
attempted in these cases
unless a BSL 3+ facility is
available to receive and
culture specimens. | clinical and laboratory
findings. It is recommended
that specimens found to be
negative for Influenza B,
Respiratory Syncytial Virus
subtype A and B,
Parainfluenza 1,
Parainfluenza 2,
Parainfluenza 3 and
Adenovirus, after
examination using RVP be
confirmed by cell culture.
Negative results do not
preclude respiratory virus
infection and should not be
used as the sole basis for
diagnosis, treatment or
other management
decisions. Positive results
do not rule out bacterial
infection, or co-infection
with other viruses. The
agent detected may not be
the
definite cause of disease.
The use of additional
laboratory testing (e.g.
bacterial culture,
immunofluorescence,
radiography) and clinical
presentation must be taken
into consideration in order
to obtain the final diagnosis
of respiratory viral infection.
Due to seasonal
prevalence, performance
characteristics for Influenza
A/H1 were established
primarily with retrospective
specimens.
The RVP assay cannot
adequately detect
Adenovirus species C, or
serotypes 7a and 41. The
RVP primers for detection
of rhinovirus cross-react
with enterovirus. A
rhinovirus reactive result | and epidemiological risk
factors. - to provide epidemiologic
information for surveillance
for influenza viruses.
Performance
characteristics for influenza
A were established when
influenza A/H3 and A/H1
were the predominant
influenza A viruses in
circulation. When other
influenza A viruses are
emerging, performance
characteristics may vary.
Testing with the influenza
H5a and H5b primer and
probe sets should not be
performed unless the
patient meets the most
current U.S. Department of
Health and Human
Services (DHHS) clinical
and epidemiologic criteria
for testing suspect A/H5
specimens. The definitive
identification of influenza
A/H5 (Asian lineage) either
directly from patient
specimens or from virus
cultures requires additional
laboratory testing, along
with clinical and
epidemiological
assessment in consultation
with national
influenza surveillance
experts.
Negative results do not
preclude influenza virus
infection and should not be
used as the sole basis for
treatment or other patient
management decisions. All
users, analysts, and any
person reporting diagnostic
results from use of this
device should be trained to |
| Item
Name | Device | Predicate | |
| | Simplexa™ Influenza A
H1N1 (2009) | xTAG Respiratory Viral
Panel - FLUA | CDC Human Influenza
Virus Real-Time RT- PCR
Detection and
Characterization Panel |
| | | should be confirmed by an
alternate method (e.g. cell
culture). Performance
characteristics for Influenza
A Virus were established
when Influenza A/H3 and
A/H1 were the predominant
Influenza A viruses in
circulation. When other
Influenza A viruses are
emerging, performance
characteristics may vary. If
infections with a 2009
H1N1 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 2009 H1N1
virulent Influenza viruses
and sent to a state or local
health department for
testing. Viral culture should
not be attempted in these
cases unless a BSL 3+
facility is available to
receive and culture
specimens. | perform and interpret the
results from this procedure
by a CDC instructor or
designee prior to use. CDC
Influenza Division will limit
the distribution of this
device to only those users
who have successfully
completed training provided
by CDC instructors or
designees. |
| Assay Targets | Influenza A
2009 H1N1 Influenza | Influenza A, Influenza A
subtype H1, Influenza A
subtype H3, Influenza B,
Respiratory Syncytial Virus
subtype A, Respiratory
Syncytial Virus subtype B,
Parainfluenza 1,
Parainfluenza 2, and
Parainfluenza 3 virus,
Human Metapneumovirus,
Rhinovirus, and
Adenovirus. | Influenza A/H1
Influenza A/H3
Influenza A/H5 (asian
lineage)
Influenza B |
| Item
Name | Device | Predicate | |
| | Simplexa™ Influenza A
H1N1 (2009) | xTAG Respiratory Viral
Panel - FLUA | CDC Human Influenza
Virus Real-Time RT- PCR
Detection and
Characterization Panel |
| Extraction
Methods | Roche MagNA Pure LC
Total Nucleic Acid Isolation
Kit,
QIAGEN QIAamp Viral
RNA Mini Kit | QIAGEN QIAamp Mini
Elute
Biomérieux EasyMag,
Biomérieux MiniMag | QIAamp® Viral RNA Mini
Kit.
Qiagen RNeasy® Mini Kit,
MagNA Pure LC RNA
Isolation Kit II
Roche MagNA Pure LC
Total Nucleic Acid Isolation
Kit, |
| Assay
Methodology | PCR-based system for
detecting the presence /
absence of viral RNA in
clinical specimens | PCR-based system for
detecting the presence /
absence of viral DNA/RNA
in clinical specimens | PCR-based system for
detecting the presence /
absence of viral RNA in
clinical specimens |
| Detection
Techniques | Multiplex assay using
different reporter dyes for
each target. | Multiplex assay using a
combination of color coded
beads and different
reporter dyes. | A panel of oligonucleotide
primers and dual-labeled
hydrolysis (TaqMan®)
probes for the qualitative
detection and differentiation
of influenza virus type and
subtype target sequences. |
| Influenza A
Viral Target | Well conserved region of
the matrix gene | Well conserved region of
the matrix gene | Well conserved region of
the matrix gene |
| H1N1 (2009)
Viral Target | Well conserved region of
the hemagglutinin gene
specific for H1N1 (2009) | n/a | n/a |
| LoD | Influenza A Strains
TCID50/mL in a range of
$1x10^{-1}$ to $2.7x10^{1}$
2009 H1N1
TCID50/mL in a range of
$1x10^{-1}$ to $2.7x10^{1}$
Please refer to detailed table
below. | Influenza A
A/PR/8/34 (TCID50/mL =
$8x10^{-1}$ )
A/Victoria/3/75 (TCID50/mL
= $1x10^{2}$ ) | Influenza A
A/New Caledonia/20/1999
(TCID50/mL = $10^{1.2}$ )
A/Hawaii/15/2001
(TCID50/mL = $10^{1.5}$ )
A/New York/55/2004
(TCID50/mL = $10^{2.2}$ )
A/Wisconsin/67/2005
(TCID50/mL = $10^{1.2}$ ) |
| Reproducibility | FLUA Inter-Assay
Total %CV range 0.0 to 4.8
FLUA Intra-Assay
Total %CV range 0.0 to 6.6
H1N1 Inter-Assay
Total %CV range 0.0 to 1.8
H1N1 Intra-Assay
Total %CV range 0.0 to 4.7 | Influenza A - low positive
%CV range 29.41 to 60.22
Influenza A - medium titer
%CV range 5.6 to 35.6 | Influenza A - 1:10 of low
positive %CV range 1.94 to
7.09
Influenza A - low positive
%CV range 2.12 to 7.89 |
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510(k) Summary of Safety and Effectiveness Simplexa ™ Influenza A H1N1 (2009) Catalog No. MOL2500 Prepared Date: May 18, 2010
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510(k) Summary of Safety and Effectiveness Simplexa™ Influenza A H1N1 (2009) Catalog No. MOL2500 Prepared Date: May 18, 2010 Page 4 of 9
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510(k) Summary of Safety and Effectiveness Simplexa™ Influenza A H1N1 (2009) Catalog No. MOL2500 Prepared Date: May 18, 2010 Page 5 of 9
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K1001 510(k) Summary of Safety and Effectiveness Simplexa ™ Influenza A H1N1 (2009) Catalog No. MOL2500 Prepared Date: May 18, 2010 Page 6 of 9
Reproducibility:
Three investigative sites assessed the device's inter-laboratory reproducibility and inter/intra-assay reproducibility. Each of the three laboratories tested eighteen samples, the Positive Control and the No Template Control, in triplicate on five different days. Each site had two operators who each ran the assay once per day, for a total of two runs per Two sites performed the extraction using the MagNA Pure LC Total Nucleic Acid Isolation Kit; one site day. performed the extraction step using the Qiagen QlAamp Viral RNA Mini Kit. Combined results for all sites are summarized below.
| FLUA Inter-Assay | Total %CV range (0.0 to 4.8) |
|---|---|
| FLUA Intra-Assay | Total %CV range (0.0 to 6.6) |
| H1N1 Inter-Assay | Total %CV range (0.0 to 1.8) |
| H1N1 Intra-Assay | Total %CV range (0.0 to 4.7) |
Limit of Detection
Simplexa™ Influenza A H1N1 (2009) Limit of Detection - FLUA
| Influenza A Strain | LoD MagNA Pure extraction
(TCID50/mL) | | LoD QIAgen extraction
(TCID50/mL) | |
|----------------------------------|------------------------------------------|----------|--------------------------------------|----------|
| | Swab | Aspirate | Swab | Aspirate |
| A/California/7/2009 NYMC x-179-A | 1.3x101 | 1.3x101 | 1.3x101 | 2.7x101 |
| A/Swine NY/02/2009 H1N1 | 1x10-1 | 1x10-1 | 1x10-1 | 1x10-1 |
| A/Solomon Island/03/06 H1 | 5x100 | 5x100 | 1x100 | 1x100 |
| A/Brisbane/59/07 H1 | 1x100 | 1x100 | 1x100 | 1x100 |
| A/Brisbane/10/07 H3 | 1x10-1 | 1x10-1 | 5x10-1 | 5x10-1 |
| A/Wisconsin/67/05 H3 | 1x10-1 | 5x10-1 | 1x10-1 | 1x10-1 |
Simplexa™ Influenza A H1N1 (2009) Limit of Detection - H1N1
| 2009 Influenza A Strain | LoD MagNA Pure extraction
(TCID50/mL) | | LoD QIAgen extraction
(TCID50/mL) | |
|----------------------------------|------------------------------------------|-----------------|--------------------------------------|-----------------|
| | Swab | Aspirate | Swab | Aspirate |
| A/California/7/2009 NYMC x-179-A | $1.3\times10^1$ | $2.7\times10^1$ | $2.7\times10^1$ | $2.7\times10^1$ |
| A/Swine NY/02/2009 H1N1 | $1\times10^1$ | $1\times10^1$ | $1\times10^1$ | $1\times10^1$ |
Analytical Reactivity
| Influenza A Strain | Estimated LoD |
|---|---|
| A/PR/8/34 H1N1 | $1x10^0$ |
| A/New Caledonia/20/99 H1N1 | $1x10^0$ |
| A/Taiwan/42/06 H1N1 | $1x10^0$ |
| A/WS/33 H1N1 | $1x10^0$ |
| A/Hong Kong/8/68 H3N2 | $1x10^0$ |
Cross-Reactivity
No cross reactivity was detected for either Influenza A or 2009 H1N1 to organisms that are closely related to influenza A or 2009 H1N1, or cause similar clinical symptoms as influenza A or 2009 H1N1, or present as normal flora in the specimen types of interest.
Interference
Potentially interfering substances were not tested with this methodology; common medications taken by study participants do not appear to inhibit the PCR process.
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510(k) Summary of Safety and Effectiveness Simplexa™ Influenza A H1N1 (2009) Catalog No. MOL2500 Prepared Date: May 18, 2010 Page 7 of 9
Clinical Agreement
Specimens were prospectively collected at three sites from patients with signs and symptoms of influenza like illness (Austin, TX (September 2009) and the New South Wales region of Australia (July - September 2009). Specimens were blinded and randomly distributed to 3 U.S. clinical laboratories for testing. Specimens were determined to be positive for 2009 H1N1 influenza by a composite reference method including the Luminex xTAG RVP Flu A target, a validated PCR assay using primer and probe sequences published by the CDC and a well characterized PCR followed by sequencing. Two results were generated for each specimen, an influenza A result and a 2009 H1N1 influenza sub-typing result. Both results must be positive to determine that a specimen is 2009 H1N1 influenza positive.
299 prospectively collected nasal/nasopharyngeal swabs and 112 nasopharyngeal aspirates were analyzed using the Simplexa™ Influenza A H1N1 (2009) assay. The data presented below are stratified by both result and specimen type. Fifteen (15) specimens (10 swabs and 5 aspirates) were excluded from the analysis because there was no consensus among the reference assays for the influenza A result. Twelve (12) specimens (9 swabs and 3 aspirates) were excluded from the 2009 H1N1 Influenza Clinical Acreement Summary tables as sequencing data used to determine subtype was not available. These 12 specimens are included in the Influenza A Clinical Agreement Summary tables.
2009 H1N1 Influenza Clinical Agreement Summary Simplexa™ Influenza A H1N1 (2009) vs. Composite Reference Result - Prospectively Collected Swabs'
| H1N1 Result - Simplexa™ Influenza A H1N1 (2009) | ||||
|---|---|---|---|---|
| Composite | ||||
| Reference Result | n | H1N1 | ||
| Detected | H1N1 | |||
| Not Detected | % Agreement | |||
| H1N1 | ||||
| Detected | 101 | 101 | 0 | % Positive Agreement |
| 100%(101/101) | ||||
| 95% CI:96.3-100% | ||||
| H1N1 | ||||
| Not Detected | 179 | 8 | 171 | % Negative Agreement |
| 95.5%(171/179) | ||||
| 95% CI:91.4-97.7% |
- Ten (10) samples were excluded from the analysis because there was no consensus among the influenza A reference assays. Nine (9) samples were excluded because sequencing results to determine sub-types were not available.
| H1N1 Result - Simplexa™ Influenza A H1N1 (2009) | |||||
|---|---|---|---|---|---|
| n | H1N1 | ||||
| Detected | H1N1 | ||||
| Not Detected | % Agreement | ||||
| Composite | |||||
| Reference Result | H1N1 | ||||
| Detected | 24 | 24 | 0 | % Positive Agreement | |
| 100%(24/24) | |||||
| 95% CI:86.2-100% | |||||
| H1N1 | |||||
| Not Detected | 80 | 6 | 74 | % Negative Agreement | |
| 92.5%(74/80) | |||||
| 95% CI:84.6-96.5% |
2009 H1N1 Influenza Clinical Agreement Summary
(1N1 (2009) vs. Composite Reference Result - Prospectively Colle
- Five (5) samples were excluded from the analysis because there was no consensus among the influenta A reference assays. Three (3) samples were excluded because sequencing results to determine sub-types were not available.
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510(k) Summary of Safety and Effecti Simplexa ™ Influenza A H1N1 (2009) Catalog No. MOL2500 Prepared Date: May 18, 2010 Page 8 of 9
Influenza A Clinical Agreement Summary
Simplexa™ Influenza A H1N1 (2009) vs. Composite Reference Result - Prospectively Collected Swabs'
| Influenza A Result - Simplexa™ Influenza A H1N1 (2009) | ||||
|---|---|---|---|---|
| n | Influenza A Detected | Influenza A Not Detected | % Agreement | |
| Composite | ||||
| Reference Result | ||||
| Influenza A | ||||
| Detected | 116 | 116 | 0 | % Positive Agreement |
| 100%(116/116) | ||||
| 95% CI:96.8-100% | ||||
| Influenza A | ||||
| Not Detected | 173 | 13 | 160 | % Negative Agreement |
| 92.5%(160/173) | ||||
| 95% CI:87.6-95.6% |
- Due to the low prevalence of other strains of intrasting period, all FLU A responses from prospectively collected sware combined to demonstrate the performance of the FLU A bi-functional fluorescent primer-probe. Of the 116 speciment to be positive for FLU A: 101 were 2009 H N1 influenza positive, zero (0) were H3N2, two (2) were not detected by the atternate PCR and could not be sequenced, and nine (9) were not sub-typed. Ten (10) samples were excluded from the analysis because there was no consensus arnong the influenza A reference assays.
Influenza A Clinical Agreement Summary
Simplexa™ Influenza A H1N1 (2009) vs. Composite Reference Result – Prospectively Collected Aspirates
| Influenza A Result - Simplexa™ Influenza A H1N1 (2009) | ||||
|---|---|---|---|---|
| n | Influenza A Detected | Influenza A Not Detected | % Agreement | |
| Influenza A | ||||
| Detected | 31 | 31 | 0 | % Positive Agreement |
| 100%(31/31) | ||||
| 95% CI:89-100% | ||||
| Influenza A | ||||
| Not Detected | 76 | 3 | 73 | % Negative Agreement |
| 96.1%(73/76) | ||||
| 95% CI:89-98.6% |
- Due to the low prevalence of other strains of intributional FLU A responses from prospecively collected aspirates were combined to demonstrate the performance of the FLU A bi-functional fluorescent primer-probe. Of the 31 specimens delermined to be positive for FLU A, 24 were 2009 H1N1 influenza positive, one (1) was sequenced but the sub-ype could not be determined, three (3) were not detected by the allernate PCR and could not be sequenced three sufficient volume to sequence to determine sub-type. Five (5) samples were excluded from the analysis because there was no consensus of the influenza A reference assays.
An additional 214 retrospectively collected nasal/nasopharyngeal swabs and 2 nasal washes from the Focus Sample Bank were also tested at 3 sites. Three (3) swab specimens were excluded from the analysis because there was no consensus among the reference assay results. One (1) swab specimen was excluded from the 2009 H1N1 Influenza Clinical Agreement Summary tables as sequencing data used to determine subtype was not available. This specimen is included in the Influenza A Clinical Agreement Summary tables.
2009 H1N1 Influenza Clinical Agreement Summary
Simplexa™ Influenza A H1N1 (2009) vs. Composite Reference Result - Retrospectively Collected Swabs
| H1N1 Result - Simplexa™ Influenza A H1N1 (2009) | ||||||
|---|---|---|---|---|---|---|
| Composite | ||||||
| Reference Result | n | H1N1 | ||||
| Detected | H1N1 | |||||
| Not Detected | Indeterminate | % Agreement | ||||
| H1N1 | ||||||
| Detected | 57 | 57 | 0 | 0 | % Positive Agreement | |
| 100%(57/57) | ||||||
| 95% CI:93.7-100% | ||||||
| H1N1 | ||||||
| Not Detected | 153 | 13 | 139 | 1 | % Negative Agreement | |
| 90.8%(139/153) | ||||||
| 95% CI:85.2-94.5% |
- Three (3) samples were excluded from the analysis because there was no consensus of the influenza A reference assays. One (1) sample was excluded from the analysis because sequencing results there was insufficient sample to perform sequencing.
Two retrospectively collected washes were found to be positive for 2009 H1N1 influenza by the composite reference method and by the Simplexa assay.
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510(k) Summary of Safety and Effectiveness
Simplexa ™ Influenza A H1N1 (2009) Catalog No. MOL2500 Prepared Date: May 18, 2010
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Influenza A Clinical Agreement Summary
Simplexa™ Influenza A H1N1 (2009) vs. Composite Reference Result - Retrospectively Collected Swabs
| Influenza A Result - Simplexa™ Influenza A H1N1 (2009) | ||||||
|---|---|---|---|---|---|---|
| n | Influenza A Detected | Influenza A Not Detected | Indeterminate | % Agreement | ||
| Composite | ||||||
| Reference Result | Influenza A Detected | 132 | 131 | 0 | 1 | % Positive Agreement |
| 99.2%(131/132) | ||||||
| 95% CI:95.8-99.9% | ||||||
| Influenza A Not Detected | 79 | 13 | 66 | 0 | % Negative Agreement | |
| 83.5%(66/79) | ||||||
| 95% CI:73.9-90.1% |
- Due to the low prevalence of other strains of influenza A during the testing period; all FLU A responses from retrospectively collected samples were combined to demonstrate the performan fluorescent primer-probe. Of the 132 specimens determined to be positive for FLU A, 57 were 2009 H1N1 influenza positive, two (2) were H1N1, 59 were H3N2, one (1) was sequenced but the sub-ype could not be determined, one (1) was indeterminate by Simplexa, 11 were not detected by the alternate PCR and one (1) did not have sufficient volume to sequence to delemine sub-lype. Three (3) samples were excluded from the analysis because of the influenza A reference assays.
Two retrospectively collected washes were found to be positive for influenza A by the composite reference method and by the Simplexa assay.
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Food and Drug Administration 10903 New Hampshire Avenue Document Mail Center - WO66-0609 Silver Spring, MD 20993-0002
Focus Diagnostics, Inc. c/o Tara Viviani Regulatory Affairs Project Manager 11331 Valley View St. Cypress, California 90630
MAY 2 4 2010
K100148 Regulation Number: Regulation Name: Regulatory Class: Class II Product Code: OOW Dated: Received: April 29, 2010
Trade/Device Name: Simplexa ™ Influenza A H1N1 (2009) 21CFR 8866.3332 Influenza A HIN1 2009 Real Time RT-PCR April 27, 2010
Dear Ms. Viviani:
Re:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration. Iisting of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into class II (Special Controls), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050. This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a
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legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours,
ValgaArs
Sally A. Hojvat, M.Sc., Ph.D Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known): K100148
Device Name:
Simplexa™ Influenza A H1N1 (2009)
:
Indications for Use:
The Focus Diagnostics Simplexa™ Influenza A H1N1 (2009) assay is intended for use on the 3M Integrated Cycler as part of the Microfluidic Molecular System for the in vitro qualitative detection and differentiation of influenza A and 2009 H1N1 influenza viral RNA in nasopharyngeal swabs (NPS), nasal swabs (NS), and nasopharyngeal aspirates (NPA) from human patients with signs and symptoms of respiratory infection in conjunction with clinical and epidemiological risk factors.
Negative results do not preclude influenza virus infection and should not be used as the sole basis for treatment or other patient management decisions.
Performance characteristics for influenza A were established during the 2009-2010 influenza season when 2009 H1N1 influenza was the predominant influenza A virus in circulation. When other Influenza A viruses are emerging, performance characteristics may vary.
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 viruses and sent to state or focal health department for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.
Prescription Use X (Part 21 CFR 801 Subpart D)
AND/OR AND/OR AND/OR
Over-The-Counter Use (21 CFR 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostics (OIVD)
Une Schif
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) k 100148