Predicate Devices

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The summary describes a standard RT-PCR assay for detecting viral RNA, with no mention of AI or ML in the device description, intended use, or performance studies.

Therapeutic

No
The device is an in vitro diagnostic (IVD) device used for the qualitative detection and differentiation of influenza A and B viral RNA to aid in diagnosis, not to treat a condition.

Diagnostic

Yes

The intended use explicitly states, "This test is intended for use as an aid in the differential diagnosis of influenza A and influenza B viral infections in humans."

SaMD (Software as a Medical Device)

No

The device description clearly states it is a multiplex Real Time RT-PCR assay that detects viral nucleic acids and involves a reaction carried out under optimized conditions in a single tube. It also mentions the use of specific hardware platforms (Life Technologies QuantStudio™ Dx, Applied Biosystems® 7500 Fast Dx, or Cepheid SmartCycler® II) to perform the reaction. This indicates it is a hardware-based assay with associated software, not a software-only medical device.

IVD (In Vitro Diagnostic)

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 for the "in vitro qualitative detection and differentiation of influenza A and influenza B viral RNA". The term "in vitro" means "in glass" or "in the lab," referring to tests performed outside of a living organism.
Sample Type: The assay uses "nasal and nasopharyngeal swabs from patients," which are biological specimens collected from the human body.
Purpose: The test is intended "as an aid in the differential diagnosis of influenza A and influenza B viral infections in humans," indicating its use in a clinical setting to help determine a patient's condition.
Device Description: The description details the process of extracting viral nucleic acids from a patient sample and performing a real-time RT-PCR reaction, which are standard techniques used in in vitro diagnostic testing.

All of these points align with the definition of an In Vitro Diagnostic device, which is a medical device intended for use in vitro for the examination of specimens derived from the human body solely or principally for the purpose of providing information concerning a physiological or pathological state, or a congenital abnormality, or to determine the compatibility of a human being with another human being, or to monitor therapeutic measures.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The Quidel Molecular Influenza A+B Assay is a multiplex Real Time RT-PCR assay for the in vitro qualitative detection and differentiation of influenza A and influenza B viral RNA in nasal and nasopharyngeal swabs from patients with signs and symptoms of respiratory infection. This test is intended for use as an aid in the differential diagnosis of influenza A and influenza B viral infections in humans in conjunction with clinical and epidemiological risk factors. The assay does not detect the presence of influenza C virus.

Negative results do not preclude influenza virus infection and should not be used as the sole basis for diagnosis, treatment or other patient management decisions.

Performance characteristics for influenza A were established during the 2011 and 2013 influenza seasons when influenza A/H3 and 2009 H1N1 influenza were 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 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.

The assay can be performed using either the Life Technologies QuantStudio™ Dx, the Applied Biosystems® 7500 Fast Dx, or the Cepheid SmartCycler® II.

Product codes (comma separated list FDA assigned to the subject device)

OZE, OOI

Device Description

The Quidel Molecular Influenza A+B Assay detects viral nucleic acids that have been extracted from a patient sample using the NucliSENS® easyMAG® automated extraction platform. A multiplex real-time RT-PCR reaction is carried out under optimized conditions in a single tube generating amplicons for each of the target viruses present in the sample. This reaction is performed utilizing the Life Technologies QuantStudio™ Dx, the Applied Biosystems® 7500 Fast Dx, or the Cepheid SmartCycler® II platform. Identification of influenza A occurs by the use of target specific primers and a fluorescentlabeled probe that hybridizes to a conserved influenza A sequence within the matrix protein gene. Identification of influenza B occurs by the use of target specific primers and fluorescent-fabeled probes that will hybridize to a conserved influenza B sequence within the neuraminidase gene.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

nasal and nasopharyngeal swabs

Indicated Patient Age Range

Not Found

Intended User / Care Setting

For prescription use only.

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

For the clinical performance study, 631 fresh swab specimens were collected for routine respiratory virus testing at three sites across the United States. A single specimen was collected per patient. The specimens were extracted with the bioMérieux easyMAG® and tested with Quidel Molecular Influenza A + B Assay using the Life Technologies QuantStudio™ Dx. The specimens were also tested with a high performance FDA-cleared Influenza A and B molecular test.

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Analytical Performance: Precision/Reproducibility
The reproducibility of the Quidel Molecular Influenza A and B Assay was evaluated at 3 laboratory sites. Reproducibility was assessed using a panel of 4 simulated samples: 2 positive samples (above LoD), a high negative (0.3x LoD) sample, and a negative sample for each virus (influenza A (A/Mexico/4108/2009) and influenza B (B/Florida/04/2006)). Panels and controls were tested at each site by 2 operators for 5 days (triplicate testing x 2 operators x 5 days x 3 sites = 90 results per level for each virus). The panels and controls were extracted using the bioMérieux easyMAG® system and tested on the Life Technologies QuantStudio™ Dx.

A supplemental study was conducted internally using a near-LoD specimen (2x LoD) for influenza A and influenza B and a negative sample. Each was extracted on three bioMérieux easyMAG® systems and then tested on three Life Technologies QuantStudio™ Dx platforms. The two samples and controls were tested by two operators per instrument for five days, each sample tested in 3 replicates, for a total of 90 results per sample for each virus for each instrument.

The data from the combined sites indicates that the Quidel Molecular Influenza A + B Assay generates reproducible results for both influenza A and influenza B viruses when tested with the Life Technologies QuantStudioTM Dx.

Limit of Detection
The analytical sensitivity (LoD) was determined using quantified (TCID50/mL) cultures of five influenza A strains and three influenza B strains, serially diluted in negative nasopharyngeal matrix. Each dilution was extracted using the NucliSENS® easyMAG® System in replicates of 20 per concentration of virus and tested on the Cepheid SmartCycler® II, the Applied Biosystems® 7500 Fast Dx, and the Life Technologies QuantStudio™ Dx platforms. LoD is defined as the lowest concentration at which at least 95% of all replicates tested positive.

Analytical reactivity (inclusivity)
The reactivity was evaluated against multiple strains of influenza A and influenza B viruses. The clinical influenza panel consisted of ten Influenza A subtype H1N1, two Influenza A subtype 2009H1N1, eight Influenza A subtype H3N2, two Influenza A subtype H5N1, and 13 Influenza B strains. An additional panel of non-clinical restricted isolates was also tested. Each panel member was extracted using the NucliSENS® easyMAG® instrument and tested in triplicate on both the Cepheid SmartCycler® II and Applied Biosystems® 7500 Fast Dx platforms.
In 2013, additional studies were performed using two new and unique strains of influenza A virus (H3N2v and H7N9). Six (6) isolates of the H3N2v strain were extracted using the NucliSENS® easyMAG® instrument and tested in triplicate on both the Life Technologies QuantStudio™ Dx and the Applied Biosystems® 7500 Fast Dx platforms. An inactivated isolate of H7N9 was extracted using the NucliSENS® easyMAG® instrument and tested in triplicate on both the Life Technologies QuantStudio™ Dx and Applied Biosystems® 7500 Fast Dx platforms.
The Quidel Molecular Influenza A+B Assay detected 100% of the influenza A (45/45) and influenza B strains (15/15) at 2 to 3x LoD levels including pandemic and avian influenza A strains and recent circulating influenza A variant strains.

Carryover and Cross-contamination Studies
An internal study was completed with the Cepheid SmartCycler® II, the Applied Biosystems® 7500 Fast Dx, and Life Technologies QuantStudio™ Dx platform where a number of PCR reactions were performed in five separate extractions and PCR runs. Each extraction run had alternating high positive and high negative samples within the same disposable. Each PCR run had alternating high positive and negative samples. All the high positive samples were positive for influenza A and influenza B (100%). All of the high negative samples were negative for influenza A and influenza B.
The data demonstrates that no carry-over or cross contamination was observed with the bioMérieux NucliSENS® easyMAG® automated nucleic acid extraction instrument and the Cepheid SmartCycler® II instrument, the Applied Biosystems® 7500 Fast Dx, or Life Technologies QuantStudio™ Dx platform.

Clinical Performance:
Performance characteristics of the Quidel Molecular Influenza A + B Assay using the Life Technologies QuantStudio™ Dx were established during a prospective study during the 2013 respiratory virus season (January to March 2013). Six hundred and thirty-one (631) fresh swab specimens were used. Four (4) of these specimens were invalid on initial testing with the subject device (0.6%, 95% Cl: 0.2% to 1.6%). Eight (8) specimens were invalid on initial and repeat testing on the comparator device (1.3%, 95% CI: 0.6% to 2.5%). A total of twelve (12) invalid specimens were removed, leaving 619 specimens for analysis.

Conclusion

When performed on the Life Technologies QuantStudio™ Dx, the Quidel Molecular Influenza A + B Assay yielded good positive and negative percent agreement when compared to a 510(k) cleared molecular device.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Clinical Performance for Influenza A (n=619):
Positive Percent Agreement (PPA): 204/204 = 100% (95% CI: 98.2% to 100%)
Negative Percent Agreement (NPA): 382/415 = 92.0% (95% CI: 89.0% to 94.3%)

Clinical Performance for Influenza B (n=619):
Positive Percent Agreement (PPA): 106/107 = 99.1% (95% CI: 94.9% to 99.8%)
Negative Percent Agreement (NPA): 502/512 = 98.0% (95% CI: 96.4% to 98.9%)

The prospective clinical study had a dual infection rate for Influenza A and Influenza B of 1.8% (11/631, 95% CI: 1.0% to 3.1%) using the Quidel Molecular Influenza A + B Assay.

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.

K112172, K113777, K092500

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

Regulation Number and Section

§ 866.3980 Respiratory viral panel multiplex nucleic acid assay.

(a)
Identification. A respiratory viral panel multiplex nucleic acid assay is a qualitative in vitro diagnostic device intended to simultaneously detect and identify multiple viral nucleic acids extracted from human respiratory specimens or viral culture. The detection and identification of a specific viral nucleic acid from individuals exhibiting signs and symptoms of respiratory infection aids in the diagnosis of respiratory viral infection when used in conjunction with other clinical and laboratory findings. The device is intended for detection and identification of a combination of the following viruses:(1) Influenza A and Influenza B;
(2) Influenza A subtype H1 and Influenza A subtype H3;
(3) Respiratory Syncytial Virus subtype A and Respiratory Syncytial Virus subtype B;
(4) Parainfluenza 1, Parainfluenza 2, and Parainfluenza 3 virus;
(5) Human Metapneumovirus;
(6) Rhinovirus; and
(7) Adenovirus.
(b)
Classification. Class II (special controls). The special controls are:(1) FDA's guidance document entitled “Class II Special Controls Guidance Document: Respiratory Viral Panel Multiplex Nucleic Acid Assay;”
(2) For a device that detects and identifies Human Metapneumovirus, FDA's guidance document entitled “Class II Special Controls Guidance Document: Testing for Human Metapneumovirus (hMPV) Using Nucleic Acid Assays;” and
(3) For a device that detects and differentiates Influenza A subtype H1 and subtype H3, FDA's guidance document entitled “Class II Special Controls Guidance Document: Testing for Detection and Differentiation of Influenza A Virus Subtypes Using Multiplex Nucleic Acid Assays.” See § 866.1(e) for the availability of these guidance documents.

Summary

0

K131728

Quidel Molecular Influenza A + B Assay 8/26/2013 Page 1 of 16

510(k) Summary

Applicant:

Quidel Corporation 10165 McKellar Court San Diego, California 92121 Telephone: 858-552-7910 Fax: 858-646-8045

Contact Information:

Ronald H. Lollar, Senior Director Clinical and Regulatory Affairs 1055 East State Street Suite 100 Athens, Ohio 45701 740-589-3300 - Corporate number 740-589-3373 - Desk phone 740-593-8437 - Fax lollar@dhiusa.com

AUG 2 9 2013

Date of preparation of 510(k) summary:

June 11, 2013

Device Name:

Trade name - Quidel Molecular Influenza A + B Assav Classification name - Respiratory viral panel multiplex nucleic acid assay Product Code - OZE Subsequent Product Code - OOI Regulation - 21 CFR 866.3980 Classification - Class II

Device Description:

The Quidel Molecular Influenza A+B Assay detects viral nucleic acids that have been extracted from a patient sample using the NucliSENS® easyMAG® automated extraction platform. A multiplex real-time RT-PCR reaction is carried out under optimized conditions in a single tube generating amplicons for each of the target viruses present in the sample. This reaction is performed utilizing the Life Technologies QuantStudio™ Dx, the Applied Biosystems® 7500 Fast Dx, or the Cepheid SmartCycler® II platform. Identification of influenza A occurs by the use of target specific primers and a fluorescentlabeled probe that hybridizes to a conserved influenza A sequence within the matrix protein gene. Identification of influenza B occurs by the use of target specific primers and fluorescent-fabeled probes that will hybridize to a conserved influenza B sequence within the neuraminidase gene.

1

Ouidel Molecular Influenza A + B Assay

The following is a summary of the procedure:

1. Sample Collection: Obtain nasal swab and nasopharyngeal swab specimens using standard techniques from symptomatic patients. These specimens are transported, stored, and processed according to established laboratory procedures.
1. Nucleic Acid Extraction: Extract Nucleic Acids from the specimens with the NucliSENS® easyMAG® System following the manufacturer's instructions using the appropriate reagents.

Prior to the extraction procedure add 20 uL of the Process Control (PRC) to each 180 uL aliquot of specimen. The PRC serves to monitor inhibitors in the extracted specimen, assures that adequate amplification has taken place and that nucleic acid extraction was sufficient.

1. Rehydration of Master Mix: Rehydrate the lyophilized Master Mix using 135uL of Rehydration Solution. The Master Mix contains oligonucleotide primers, fluorophore and quencher-labeled probes targeting highly conserved regions of the influenza A and influenza B viruses as well as the process control sequence. The primers are complementary to highly specific and conserved regions in the genome of these viruses. The probes are dual labeled with a reporter dye attached to the 5-end and a quencher attached to the 3' -end. The rehydrated Master Mix is sufficient for eight reactions.
1. Nucleic Acid Amplification and Detection: Add 15 uL of the rehydrated Master Mix to each reaction tube or plate well. 5 uL of extracted nucleic acids (specimen with PRC) is then added to the reaction tube or plate well. Place the tube into the Cepheid SmartCycler® II instrument, or place the plate into either the Applied Biosystems® 7500 Fast Dx instrument or Life Technologies QuantStudioTM Dx.

Once the reaction tube or plate is added to the instrument, the assay protocol is initiated. This protocol initiates reverse transcription of the RNA targets generating complementary DNA, and the subsequent amplification of the target sequences occurs. The Quidel Molecular Influenza A+B Assay is based on TaqMan® chemistry, and uses an enzyme with reverse transcriptase, DNA polymerase, and 5'-3' exonuclease activities. During DNA amplification, this enzyme cleaves the probe bound to the complementary DNA sequence, separating the quencher dye from the reporter dye. This step generates an increase in fluorescent signal upon excitation by a light source of the appropriate wavelength. With each cycle, additional dye molecules are separated from their quenchers resulting in additional signal. If sufficient

2

510(k) Summary	Quidel Molecular Influenza A + B Assay
	8/26/2013
	Page 3 of 16

fluorescence is achieved the sample is reported as positive for the detected target sequence

Intended Use:

The Quidel Molecular Influenza A+B Assay is a multiplex Real Time RT-PCR assay for the in vitro qualitative detection and differentiation of influenza A and influenza B viral RNA in nasal and nasopharyngeal swabs from patients with signs and symptoms of respiratory infection. This test is intended for use as an aid in the differential diagnosis of influenza A and influenza B viral infections in humans in conjunction with clinical and epidemiological risk factors. The assay does not detect the presence of influenza C virus.

Negative results do not preclude influenza virus infection and should not be used as the sole basis for diagnosis, treatment or other patient management decisions.

Performance characteristics for influenza A were established during the 2011 and 2013 influenza seasons when influenza A/H3 and 2009 H1N1 influenza were 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 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.

The assay can be performed using the Life Technologies OuantStudio™ Dx. the Applied Biosystems® 7500 Fast Dx, or the Cepheid SmartCycler® II.

Conditions for Use:

For prescription use only.

Device Comparison

The Quidel Molecular Influenza A+B Assay was compared to Prodesse ProFlu+ ("Comparator Device"). The characteristics of Quidel Molecular Influenza A+B Assay ("Subject Device") and the two predicates. Quidel Molecular Influenza A+B Assay (previously cleared for use with two other instruments) and the Prodesse ProFlu+ are described in the table below:

3

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8/26/2013
Page 4 of 16 .

Device Comparison
Item	Subject Device
Quidel Molecular
Influenza A+B Assay	Comparator Device
Quidel Molecular
Influenza A+B Assay
(K112172, K113777)	Comparator Device
Prodesse ProFlu+
(K092500)
Intended Use	The Quidel Molecular
Influenza A+B Assay
is a multiplex Real
Time RT-PCR assay
for the in vitro
qualitative detection
and differentiation of
influenza A and
influenza B viral RNA
in nasal and
nasopharyngeal swabs
from patients with
signs and symptoms
of respiratory
infection. This test is
intended for use as an
aid in the differential
diagnosis of influenza
A and influenza B
viral infections in
humans in
conjunction with
clinical and
epidemiological risk
factors. The assay
does not detect the
presence of influenza
C virus.

Negative results do
not preclude influenza
virus infection and
should not be used as
the sole basis for
diagnosis, treatment
or other patient | The Quidel Molecular
Influenza A+B Assay
is a multiplex Real
Time RT-PCR assay
for the in vitro
qualitative detection
and differentiation of
influenza A and
influenza B viral RNA
in nasal and
nasopharyngeal swabs
from patients with
signs and symptoms
of respiratory
infection. This test is
intended for use as an
aid in the differential
diagnosis of influenza
A and influenza B
viral infections in
humans in
conjunction with
clinical and
epidemiological risk
factors. The assay
does not detect the
presence of influenza
C virus.

Negative results do
not preclude Influenza
virus infection and
should not be used as
the sole basis for
diagnosis, treatment
or other patient | The ProFluTM+ Assay
is a multiplex Real-
Time PCR (RT-PCR)
in vitro diagnostic
test for the rapid and
qualitative detection
and discrimination of
Influenza A Virus,
Influenza B Virus,
and Respiratory
Syncytial Virus
(RSV) nucleic acids
isolated and purified
from nasopharyngeal
(NP) swab specimens
obtained from
symptomatic patients.
This test is intended
for use to aid in the
differential diagnosis
of Influenza A,
Influenza B and RSV
viral infections in
humans and is not
intended to detect
Influenza C.

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Page 5 of 16

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8/26/2013 Page 6 of 16

6

Quidel Molecular Influenza A + B Assay

510(k) Summary

. .

7

Quidel Molecular Influenza A + B Assay

	510(k) Summary

8/26/2013 Page 8 of 16

Device Comparison
Item	Subject Device
Quidel Molecular
Influenza A+B Assay	Comparator Device
Quidel Molecular
Influenza A+B Assay
(K112172, K113777)	Comparator Device
Prodesse ProFlu+
(K092500)
Analytical sensitivity
(LoD), as defined as
the lowest
concentration at
which 95% of all
replicates tested
positive, ranged from
$10^1$ to $10^0$
TCID₅₀/mL.	the lowest
concentration at
which 95% of all
replicates tested
positive, ranged from
$10^1$ to $10^0$
TCID₅₀/mL.	which 95% of all
replicates tested
positive, ranged from
$10^2$ to $10^{-1}$
TCID₅₀/mL.

Analytical Performance:

Precision/Reproducibility:

The reproducibility of the Quidel Molecular Influenza A and B Assay was evaluated at 3 laboratory sites. Reproducibility was assessed using a panel of 4 simulated samples. The panels consisted of 2 positive samples (above LoD), a high negative (0.3x LoD) sample and a negative sample for each virus, influenza A (A/Mexico/4108/2009) and influenza B (B/Florida/04/2006). Panels and controls were tested at each site by 2 operators for 5 days (triplicate testing x 2 operators x 5 days x 3 sites = 90 results per level for each virus). The panels and controls were extracted using the bioMérieux easyMAG® system and tested on the Life Technologies QuantStudio™ Dx.

Reproducibility Results - Life Technologies QuantStudio™ Dx
Panel
Member
ID	Site 1		Site 2	Site 3	Combined Site Data
	Rate of
Detection	AVE
Ct	%CV	Rate of
Detection	AVE
Ct	%CV	Rate of
Detection	AVE
Ct	%CV	Rate of
Detection	AVE Ct	%CV
Influenza
A High
Negative
(0.3 x
LoD)	25/30	37.4

| 3.8 | 13/30 | 38.2
| 2.6 | 4/28** | 37.5
| 4.2 | 42/88** | 37.2 | 3.6 |
| Influenza
A Positive
1 | 30/30 | 27.5 | 2.5 | 30/30 | 27.7 | 2.1 | 29/29** | 27.9 | 4.3 | 89/89** | 27.7 | 3.1 |
| Influenza
A Positive
2 | 30/30 | 26.4 | 1.7 | 30/30 | 26.4 | 1.8 | 30/30 | 27.0 | 6.1 | 90/90 | 26.6 | 3.9 |
| Influenza | 0/30 | N/A | N/A | 0/30 | N/A | N/A | 0/30 | N/A | N/A | 0/90 | N/A | N/A |

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510(k) Summary

8/26/2013 Page 9 of 16

Reproducibility Results - Life Technologies QuantStudio™ Dx
Panel
Member ID	Site 1			Site 2			Site 3			Combined Site Data
	Rate of Detection	AVE Ct	%CV	Rate of Detection	AVE Ct	%CV	Rate of Detection	AVE Ct	%CV	Rate of Detection	AVE Ct	%CV
A Negative
Influenza
B High
Negative
(0.3 x LoD)	28/30	37.7*	3.1	23/30	37.8*	3.6	14/28**	37.7*	2.7	65/88**	37.7	3.2
Influenza
B Positive
1	30/30	25.8	1.8	30/30	25.4	1.5	29/29	25.9	8.7	89/89**	25.7	5.2
Influenza
B Positive
2	30/30	24.4	1.8	30/30	24.0	1.7	30/30	24.9	8.8	90/90	24.4	5.5
Influenza
B Negative	0/30	N/A	N/A	0/30	N/A	N/A	0/30	N/A	N/A	0/90	N/A	N/A
Influenza
A Positive
Control	30/30	28.7	2.7	30/30	30.7	2.1	30/30	31.7	9.2	90/90	30.4	7.1
Influenza
B Positive
Control	30/30	27.9	1.2	30/30	27.5	1.8	30/30	29.9	6.9	90/90	28.7	6.6
Negative
Control	0/30	N/A	N/A	0/30	N/A	N/A	0/30	N/A	N/A	0/90	N/A	N/A

Average Ct of positive results only

** One or more of the replicates was invalid due to non-detection of the PRC

Upon review of the Life Technologies QuantStudio™ Dx reproducibility data it was determined that the concentration of the positive samples was higher than expected. A supplemental study was conducted internally using a near-LoD specimen. In this study, a sample with a low positive concentration (2x LoD) for influenza A and for influenza B and a negative sample were each extracted on three bioMérieux easyMAG® systems and then tested on three Life Technologies QuantStudio™ Dx platforms. The two samples and controls were tested by two operators per instrument for five days, each sample tested in 3 replicates, for a total of 90 results per sample for each virus for each instrument (2 operators x 5 days x 3 instruments x 3 replicates). This data is presented separately as a supplemental study.

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8/26/2013 Page 10 of 16

Reproducibility Results - Life Technologies QuantStudio™ Dx - Supplemental Study
Panel
Member ID
(TCID50/mL)	QuantStudio™ #1
Rate of
Detection	QuantStudio™ #1
AVE
Ct	QuantStudio™ #1
%CV	QuantStudio™ #2
Rate of
Detection	QuantStudio™ #2
AVE
Ct	QuantStudio™ #2
%CV	QuantStudio™ #3
Rate of
Detection	QuantStudio™ #3
AVE
Ct	QuantStudio™ #3
%CV	Combined Instrument Data
Rate of
Detection	Combined Instrument Data
AVE
Ct	Combined Instrument Data
%CV
Influenza A
Low
Positive
(3.90E+01)	30/30	35.1	3.5	30/30	33.7	4.6	30/30	35.7	3.1	90/90	34.8	4.4
Influenza A
Negative	0/30	N/A	N/A	0/30	N/A	N/A	0/30	N/A	N/A	0/90	N/A	N/A
Influenza B
Low
Positive
(2.01E+02)	30/30	35.2	3.1	30/30	34.5	3.2	30/30	35.6	2.7	90/90	35.1	3.2
Influenza B
Negative	0/30	N/A	N/A	0/30	N/A	N/A	0/30	N/A	N/A	0/90	N/A	N/A
Influenza A
Positive
Control	30/30	31.0	4.6	30/30	30.9	6.1	30/30	31.3	4.0	90/90	31.1	5.0
Influenza B
Positive
Control	30/30	27.7	1.5	30/30	27.7	3.2	30/30	28.1	1.3	90/90	27.8	2.3
Negative
Control	0/30	N/A	N/A	0/30	N/A	N/A	0/30	N/A	N/A	0/90	N/A	N/A

The data from the combined sites indicates that the Quidel Molecular Influenza A + B Assay generates reproducible results for both influenza A and influenza B viruses when tested with the Life Technologies QuantStudioTM Dx.

Limit of Detection

The analytical sensitivity (limit of detection or LoD) of the Quidel Molecular Influenza A+B Assay was determined using quantified (TCID50/mL) cultures of five influenza A strains and three influenza B strains, serially diluted in negative nasopharyngeal matrix. Each dilution was extracted using the NucliSENS® easyMAG® System in replicates of 20 per concentration of virus and tested on both the Cepheid SmartCycler® II, the Applied Biosystems® 7500 Fast Dx, and the Life Technologies QuantStudio™ Dx platforms. Analytical sensitivity (LoD) is defined as the lowest concentration at which at least 95% of all replicates tested positive. The demonstrated LoD for each of the three instruments is shown below.

10

Quidel Molecular Influenza A + B Assay

510(k) Summary

8/26/2013 Page 11 of 16

| Strain | Final LOD
(TCID50/mL)
Cepheid
SmartCycler® II
(K113777) | Final LOD
(TCID50/mL)
Applied
Biosystems®
7500 Fast Dx
(K112172) | Final LOD
(TCID50/mL)
Life
Technologies
QuantStudio™
Dx
(K131728) |
|--------------------------------------|---------------------------------------------------------------------|---------------------------------------------------------------------------------|-------------------------------------------------------------------------------------|
| A/Mexico/4108/2009
(H1N1) | 2.40E+01 | 4.80E+01 | 2.0E+01 |
| A1/Mal/302/54
(H1N1) | 7.00E+00 | 1.60E+01 | N/A |
| A/Victoria/3/75
(H3N2) | 3.10E+01 | 9.20E+01 | N/A |
| A/Brisbane/59/2007
(H1N1) | N/A | 3.33E+01 | 1.00E+02 |
| A/Brisbane (H3N2) | N/A | 1.00E+01 | 5.00E+01 |
| B/RCHIN 8/05 | 1.80E+00 | 1.20E+01 | N/A |
| B/Brisbane '09-'10
Vaccine Strain | N/A | 1.50E+02 | 1.00E+02 |
| B/Florida/04/2006 | 6.00E+00 | 4.30E+01 | 1.00E+02 |
| B/Malaysia/25/06/04 | 1.30E+00 | 5.70E+00 | 1.00E+00 |

Analytical reactivity (inclusivity)

The reactivity of the Quidel Molecular Influenza A+B Assay was evaluated against multiple strains of influenza A and influenza B viruses. The clinical influenza panel consisted of ten Influenza A subtype H1N1, two Influenza A subtype 2009H1N1, eight Influenza A subtype H3N2, two Influenza A subtype H5N1, and 13 Influenza B strains. An additional panel of non-clinical restricted isolates was also tested. Each panel member was extracted using the NucliSENS® easyMAG® instrument and tested in triplicate on both the Cepheid SmartCycler® II and Applied Biosystems® 7500 Fast Dx platforms.

In 2013 additional studies were performed using two new and unique strains of influenza A virus (H3N2v and H7N9). Six (6) isolates of the H3N2v strain were extracted using the NucliSENS® easyMAG® instrument and tested in triplicate on both the Life Technologies QuantStudio™ Dx and the Applied Biosystems® 7500 Fast Dx platforms. An inactivated isolate of H7N9 was extracted using the NucliSENS® easyMAG® instrument and tested in triplicate on both the Life Technologies QuantStudio™ Dx and Applied Biosystems® 7500 Fast Dx platforms.

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8/26/2013 Page 12 of 16

The Quidel Molecular Influenza A+B Assay detected 100% of the influenza A (45/45) and influenza B strains (15/15) at 2 to 3x LoD levels including pandemic and avian influenza A strains and recent circulating influenza A variant strains.

Influenza A Viruses
Subtype	Strain	TCID50/mL	A	B
2009 H1N1	H1N1 A/California/07/2009	1.45E+02	Positive	Negative
H1N1	A/New Caledonia/20/1999	1.12E+02	Positive	Negative
H1N1	A/New Jersey/8/76	3.80E+02	Positive	Negative
H1N1	A/PR/8/34	5.89E+02	Positive	Negative
H1N1	A/NWS/33	NA	Positive	Negative
H1N1	A/Denver/1/57	1.26E+02	Positive	Negative
H1N1	A/FM/1/47	3.80E+02	Positive	Negative
2009 H1N1	A/Mexico/4108/2009	1.40E+02	Positive	Negative
H1N1	A1/Mal/302/54	4.19E+02	Positive	Negative
H1N1	A/Taiwan/42/06	3.39E+02	Positive	Negative
H1N1	A/Brisbane/59/07	7.24E+01	Positive	Negative
H1N1	A/Solomon Islands/3/06	1.41E+01	Positive	Negative
H3N2	A/WI/629-2/2008 (H3N2)	2.00E+02	Positive	Negative
H1N1	A/WI/629-S7(D02473)/2009
(H1N1pdm)	2.00E+02	Positive	Negative
H1N1	A/WI/629-S5 (D02312)/2009
(H1N1pdm)	2.00E+02	Positive	Negative
H3N2	A/Hong Kong/8/68	1.15E+02	Positive	Negative
H3N2	A/Wisconsin/67/2005	7.24E+02	Positive	Negative
H3N2	A/Aichi/2/68	4.17E+02	Positive	Negative
H3N2	A/Port Chalmers/1/73	4.57E+02	Positive	Negative
H3N2	A/Perth/16/2009	9.83E+02	Positive	Negative
H3N2	A/Uruguay/7/16/2007	1.03E+02	Positive	Negative
H3N2	A/Victoria/3/75	2.19E+02	Positive	Negative
H3N2	A/Brisbane/10/07	4.17E+02	Positive	Negative
H3N2v	A/Indiana/10/11	5.90E+01	Positive	Negative
H3N2v	A/Kansas/13/9	4.90E+01	Positive	Negative
H3N2v	A/Pennsylvania/14/10	4.80E+01	Positive	Negative
H3N2v	A/Victoria/361/11	5.20E+01	Positive	Negative
H3N2v	A/Minnesota/11/10	4.60E+01	Positive	Negative
H3N2v	A/West Virginia/6/11	5.00E+01	Positive	Negative
H7N9*	A/ANHUI/1/2013	3.95E+03*	Positive	Negative

Inactivated virus - relative EID50 Titer/mL

12

8/26/2013 Page 13 of 16

Influenza B Viruses
Strain	TCID50/mL	A	B
B/HongKong/5/72	6.67E+02	Negative	Positive
B/Panama/45/90	1.02E+02	Negative	Positive
B/Florida/02/2006	3.16E+02	Negative	Positive
B/Florida/04/2006	3.80E+02	Negative	Positive
B/Florida/07/2004	1.26E+02	Negative	Positive
B/Malaysia/25/06/04	3.41E+02	Negative	Positive
B/Maryland/1/59	1.15E+02	Negative	Positive
B/Allen/45	4.17E+02	Negative	Positive
B/Taiwan/2/62	1.51E+02	Negative	Positive
B/Russia/69	2.19E+02	Negative	Positive
B/Mass/3/66	1.38E+02	Negative	Positive
B/Lee/40	1.95E+02	Negative	Positive
B/GL/1739/54	6.30E+02	Negative	Positive

The following avian strains were tested as cultured isolates in a BS-3 facility.

Non-clinical Restricted Influenza A Viruses
Subtype	Strain	TCID50/mL	A	B
H2N2	A/Mallard/NY/6750/78 (H2N2)	2.00E+02	Positive	Negative
H7N3	A/Chicken/NJ/15086-3/94 (H7N3)	2.00E+02	Positive	Negative
H9N2	A/Chicken/NJ/12220/97 (H9N2)	2.00E+02	Positive	Negative
H4N8	A/Mallard/OH/338/86 (H4N8)	2.00E+02	Positive	Negative
H6N2	A/Chicken/CA/431/00 (H6N2)	2.00E+02	Positive	Negative
H8N4	A/Blue Winged Teal/LA/B174/86
(H8N4)	2.00E+02	Positive	Negative
H5N1	A/Anhui/01/2005(H5N1)-PR8-
IBCDC-RG5	2.00E+02	Positive	Negative
H10N7	A/GWT/LA/169GW/88 (H10N7)	2.00E+02	Positive	Negative
H11N9	A/Chicken/NJ/15906-9/96 (H11N9)	2.00E+02	Positive	Negative
H12N5	A/Duck/LA/188D/87 (H12N5)	2.00E+02	Positive	Negative
H13N6	A/Gull/MD/704/77 (H13N6)	2.00E+02	Positive	Negative
H14N5	A/Mallard/GurjevRussia/262/82
(H14N5)	2.00E+02	Positive	Negative
H15N9	A/Shearwater/Australia/2576/79
(H15N9)	2.00E+02	Positive	Negative
H16N3	A/Shorebird/DE/172/2006(H16N3)	2.00E+02	Positive	Negative

۰۷ ، ۱۰ ، ۱۳۹۶ ،

• • .

・バン・

13

Carryover and Cross-contamination Studies

An internal study was completed with the Cepheid SmartCycler® II, the Applied Biosystems® 7500 Fast Dx, and Life Technologies QuantStudio™ Dx platform where a number of PCR reactions were performed in five separate extractions and PCR runs. Each extraction run had alternating high positive and high negative samples within the same disposable. Each PCR run had alternating high positive and negative samples. All the high positive samples were positive for influenza A and influenza B (100%). All of the high negative samples were negative for influenza A and influenza B. The data demonstrates that no carry-over or cross contamination was observed with the bioMérieux NucliSENS® easyMAG® automated nucleic acid extraction instrument and the Cepheid SmartCycler® II instrument, the Applied Biosystems® 7500 Fast Dx, or Life Technologies QuantStudio™ Dx platform.

Analytical Specificity (Cross-reactivity)

Please see K113777 for Analytical Specificity (Cross-Reactivity) studies.

Analytical Specificity - Interfering Substances

Please see K113777 for Analytical Specificity (Interfering Substances) studies.

Clinical Performance:

Performance characteristics of the Quidel Molecular Influenza A + B Assay using the Life Technologies QuantStudio™ Dx were established during a prospective study during the 2013 respiratory virus season (January to March 2013). Six hundred and thirty-one (631) fresh swab specimens that were collected for routine respiratory virus testing were used for this study at three sites across the United States. A single specimen was collected per patient. The specimens were extracted with the bioMérieux easyMAG® and tested with Quidel Molecular Influenza A + B Assay using the Life Technologies QuantStudio™ Dx. The specimens were also tested with a high performance FDA-cleared Influenza A and B molecular test.

Age and Gender Distribution
Sex	F	M
Total	339	292
60 years	58 (17.1%)	39 (13.4%)
Total	339	292

The gender and age demographics

14

Quidel Molecular Influenza A + B Assay

510(k) Summary

Six hundred and thirty-one (631) fresh swab specimens were tested by both the subject and comparator device for influenza A and influenza B viral RNA. Four (4) of these specimens were invalid on initial testing with the subject device (0.6%, 95% Cl: 0.2% to 1.6%). Re-testing of the specimens according to the Interpretation algorithm described above also yielded invalid results. Eight (8) specimens were invalid on initial and repeat testing (as per the device's PI) on the comparator device (1.3%, 95% CI: 0.6% to 2.5%). A total of twelve (12) invalid specimens have been removed from additional analysis. The table below details the performance of the Quidel Influenza A + B Assay on the QuantStudio™ Dx with the remaining 619 specimens when compared to a commercially available FDA-cleared RT-PCR influenza detection device.

Influenza A
	Comparator: FDA-cleared RT-PCR
device
Quidel
Molecular	Positive	Negative	Total
Positive	204	33	237
Negative	0	382	382
Total	204	415	619
			95% CI
Positive Percent
Agreement	204/204	100%	98.2% to
100%
Negative Percent
Agreement	382/415	92.0%	89.0% to
94.3%

Influenza B
	Comparator: FDA-cleared RT-PCR device
Quidel Molecular	Positive	Negative	Total
Positive	106	10	116
Negative	1	502	503
Total	107	512	619
			95% CI
Positive Percent
Agreement	106/107	99.1%	94.9% to
99.8%
Negative Percent
Agreement	502/512	98.0%	96.4% to
98.9%

The prospective clinical study had a dual infection rate for Influenza A and Influenza B of 1.8% (11/631, 95% CI: 1.0% to 3.1%) using the Quidel Molecular Influenza A + B Assay. Three (3) of these dual infections were concordant with the FDA-cleared RT-PCR device comparator assay. Six (6) of

15

these dual infections were discordant with the influenza A results from the FDA-cleared RT-PCR device comparator assay. Two (2) of these dual infections were discordant with the influenza B results from the FDA-cleared RT-PCR device comparator assay.

Conclusion

When performed on the Life Technologies QuantStudio™ Dx, the Quidel Molecular Influenza A + B Assay yielded good positive and negative percent agreement when compared to a 510(k) cleared molecular device.

16

Image /page/16/Picture/1 description: The image shows the seal of the Department of Health & Human Services (HHS) of the United States. The seal features a stylized eagle with three stripes representing the three branches of government. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the eagle.

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

August 29, 2013

Ronald H. Lollar Senior Director, Clinical and Regulatory Affairs Quidel Corporation 1055 East State Street, Suite 100 Athens, OH 45701

Re: K131728

Trade/Device Name: Quidel Molecular Influenza A + B Assay Regulation Number: 21 CFR 866.3980 Regulation Name: Respiratory viral panel multiplex nucleic assay Regulatory Class: Class II Product Code: OZE, OOI Dated: June 11, 2013 Received: June 12, 2013

Dear Mr. Lollar:

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, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to 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 Part 801); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set

17

Page 2 - Ronald H. Lollar

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.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Small Manufacturers, International and Consumer Assistance at its tollfree number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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/MedicalDevices/Resourcesfor You/Industry/default.htm.

Sincerely yours,

Sally A. Hojvat -S

Sally A. Hojvat, M. Sc., Ph.D. Director, Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health (OIR) Center for Devices and Radiological Health

Enclosure

18

Indications for Use

510(k) Number (if known): K131728

Device Name: Quidel Molecular Influenza A+B Assay

Indications For Use:

The Quidel Molecular Influenza A+B Assay is a multiplex Real Time RT-PCR assay for the in vitro qualitative detection and differentiation of influenza A and influenza B viral RNA in nasal and nasopharyngeal swabs from patients with signs and symptoms of respiratory infection. This test is intended for use as an aid in the differential diagnosis of influenza A and influenza B viral infections in humans in conjunction with clinical and epidemiological risk factors. The assay does not detect the presence of influenza C virus.

Negative results do not preclude influenza virus infection and should not be used as the sole basis for diagnosis, treatment or other patient management decisions.

Performance characteristics for influenza A were established during the 2011 and 2013 influenza seasons when influenza A/H3 and 2009 H1N1 influenza were 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 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.

The assay can be performed using either the Life Technologies QuantStudio™ Dx, the Applied Biosystems® 7500 Fast Dx, or the Cepheid SmartCycler® II.

Prescription Use x
(Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 807 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)

AND/OR

Concurrence of Center for Devices and Radiological Health (CDRH)

Tamara V. Feldblyum -S 2013.08.29 12:46:08 -04'00'

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