QUIDEL MOLECULAR RSV + HMPV ASSAY

• K Number: K131813
• Device Name: QUIDEL MOLECULAR RSV + HMPV ASSAY
• Manufacturer: QUIDEL CORP.
• Date Cleared: 2013-09-06 ( 78 days)
• Product Code: OCC OEM
• Regulation Number: 866.3980

Intended Use

The Quidel Molecular RSV + hMPV Assay is a multiplex Real-Time PCR (RT-PCR) assay for the qualitative detection and identification of respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) ribonucleic acid (RNA) extracted from nasal and nasopharyngeal swab specimens from patients with signs and symptoms of respiratory infection. This in vitro diagnostic test is intended to aid in the differential diagnosis of RSV and hMPV infections in humans in conjunction with clinical and epidemiological risk factors. This test is not intended to differentiate the two subtypes of RSV or the four genetic sub-lineages of hMPV. Negative results do not preclude RSV infection and/or hMPV infection and should not be used as the sole basis for diagnosis, treatment or other patient management decisions. Conversely, 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 and clinical presentation must be considered in order to obtain the final diagnosis of respiratory viral infection. The Quidel Molecular RSV + hMPV Assay can be performed using either the Life Technologies QuantStudio™ Dx RT-PCR Instrument, the Applied Biosystems® 7500 Fast Dx RT-PCR Instrument, or the Cepheid SmartCycler® II System.

Device Description

The Quidel Molecular RSV + hMPV Assay detects viral nucleic acids that have been extracted from a patient sample using the bioMérieux NucliSENS easyMAG automated extraction platform. A multiplex 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 Cepheid SmartCycler II, the Applied Biosystems 7500 Fast Dx. or the Life Technologies QuantStudio Dx. Identification of RSV, hMPV, and the process control (PRC) occurs by the use of target-specific primers and fluorescent-labeled probes that hybridize to conserved regions in the genomes of RSV and hMPV and the PRC.

Predicate Devices

K092500, K082688

Reference Devices

K122189

AI/ML (Artificial Intelligence / Machine Learning)

No
The summary describes a standard RT-PCR assay for detecting viral RNA. There is no mention of AI, ML, or any algorithms that would suggest their use in the analysis or interpretation of the results. The performance studies focus on analytical and clinical agreement with comparator methods, not on the performance of an AI/ML model.

Therapeutic

No
Explanation: This device is an in vitro diagnostic test for detecting RSV and hMPV from patient samples, intended to aid in diagnosis, not to treat or cure a disease.

Diagnostic

Yes

Explanation: The "Intended Use / Indications for Use" section explicitly states, "This in vitro diagnostic test is intended to aid in the differential diagnosis of RSV and hMPV infections in humans in conjunction with clinical and epidemiological risk factors." This directly indicates its role as a diagnostic tool.

SaMD (Software as a Medical Device)

No

The device is an in vitro diagnostic test that involves physical samples, extraction, and RT-PCR reactions performed on specific hardware instruments. While software is likely involved in the analysis of the RT-PCR data, the core of the device is a chemical assay and associated hardware, not software alone.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

The "Intended Use / Indications for Use" section explicitly states: "This in vitro diagnostic test is intended to aid in the differential diagnosis of RSV and hMPV infections in humans in conjunction with clinical and epidemiological risk factors."

This statement clearly identifies the device as an in vitro diagnostic test.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The Quidel Molecular RSV + hMPV Assay is a multiplex Real-Time PCR (RT-PCR) assay for the qualitative detection and identification of respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) ribonucleic acid (RNA) extracted from nasal and nasopharyngeal swab specimens from patients with signs and symptoms of respiratory infection. This in vitro diagnostic test is intended to aid in the differential diagnosis of RSV and hMPV infections in humans in conjunction with clinical and epidemiological risk factors. This test is not intended to differentiate the two subtypes of RSV or the four genetic sub-lineages of hMPV.

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

Conversely, 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 and clinical presentation must be considered in order to obtain the final diagnosis of respiratory viral infection.

The Quidel Molecular RSV + hMPV Assay can be performed using either the Life Technologies QuantStudio™ Dx RT-PCR Instrument, the Applied Biosystems® 7500 Fast Dx RT-PCR Instrument, or the Cepheid SmartCycler® II System.

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

OEM, OCC

Device Description

The Quidel Molecular RSV + hMPV Assay detects viral nucleic acids that have been extracted from a patient sample using the bioMérieux NucliSENS easyMAG automated extraction platform. A multiplex 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 Cepheid SmartCycler II, the Applied Biosystems 7500 Fast Dx. or the Life Technologies QuantStudio Dx. Identification of RSV, hMPV, and the process control (PRC) occurs by the use of target-specific primers and fluorescent-labeled probes that hybridize to conserved regions in the genomes of RSV and hMPV and the PRC.

The following is a summary of the procedure:

• Sample Collection: Obtain nasal or nasopharyngeal swab specimens using standard techniques from symptomatic patients. Transport, store, and process these specimens according to established laboratory procedures.
• Nucleic Acid Extraction: Extract nucleic acids from the specimens with the BioMérieux NucliSENS easyMAG System following the manufacturer's instructions and using the appropriate reagents. Prior to the extraction procedure. add 20 uL of the 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 confirms that the nucleic acid extraction was sufficient.
• Rehydration of Master Mix: Rehydrate the lyophilized Master Mix using the Rehydration Solution. The Master Mix contains oligonucleotide primers and fluorophore/quencher-labeled probes that target conserved regions of RSV and hMPV. as well as the PRC.
• Nucleic Acid Amplification and Detection: Add 15 uL of the rehydrated Master Mix to each reaction tube or plate well. Then add 5 µL of extracted nucleic acids (specimen with PRC) to the plate well or appropriately labeled reaction tube. Place the tube or plate into the SmartCycler II, 7500 Fast Dx, or the Life Technologies QuantStudio Dx instruments.

Once the reaction tube or plate is added to the instrument, initiate the assay protocol. This protocol initiates reverse transcription of the RNA targets. generating complementary DNA and the subsequent amplification of the target amplicons. The Quidel Molecular RSV + hMPV Assay is based on TagMan 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 fluorescence is achieved, the sample is reported as positive for the detected nucleic acid.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Nasal, nasopharyngeal

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

Not Found

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

Analytical Performance: Reproducibility

• Study Type: Reproducibility study
• Sample Size: 90 results per level for each virus (RSV and hMPV) at each site. Total results: for RSV, 39/90 for high negative, 89/90 for low positive, 90/90 for medium positive, 0/90 for negative and negative control, 90/90 for positive control. For hMPV, 52/90 for high negative, 90/90 for low positive, 90/90 for medium positive, 0/90 for negative and negative control, 90/90 for positive control.
• Data Source: Simulated samples, RSV-A Long strain and hMPV-A2 strain.
• Key Results: The Quidel Molecular RSV + hMPV Assay generated reproducible results for RSV and hMPV when tested with the Life Technologies QuantStudio Dx.
  • Combined Sites RSV:
    • 5X LoD: Detection % 100%, Ave. Ct 30.6, STDEV 1.3, %CV 4%
    • 2X LoD: Detection % 98.9%, Ave. Ct 33.1, STDEV 1.9, %CV 6%
    • 0.3X LoD: Detection % 43.3%, Ave. Ct 37.1, STDEV 1.4, %CV 4%
    • Negative: Detection % 0%
    • Positive Control: Detection % 100%, Ave. Ct 31.9, STDEV 2.3, %CV 7%
    • Negative Control: Detection % 0%
  • Combined Sites hMPV:
    • 5X LoD: Detection % 100%, Ave. Ct 28.6, STDEV 0.8, %CV 3%
    • 2X LoD: Detection % 100%, Ave. Ct 30.3, STDEV 1.0, %CV 3%
    • 0.15X LoD: Detection % 57.8%, Ave. Ct 36.0, STDEV 1.6, %CV 4%
    • Negative: Detection % 0%
    • Positive Control: Detection % 100%, Ave. Ct 28.3, STDEV 0.8, %CV 3.0%
    • Negative Control: Detection % 0%

Analytical Performance: Precision

• Study Type: Precision study
• Key Results: The data from this study indicates that when tested on the Life Technologies QuantStudio Dx Real-Time PCR Instrument, the Quidel Molecular RSV + hMPV Assay produces repeatable, precise results.

Analytical Performance: Limit of Detection (LoD)

• Study Type: Analytical sensitivity study
• Key Results: The analytical sensitivity (LoD) is defined as the lowest concentration at which 95% of all replicates tested positive.
  • RSV A: 6.29E-01 TCID50/mL
  • RSV B: 2.25E-01 TCID50/mL
  • hMPV-A1: 8.73E+00 TCID50/mL
  • hMPV-A2: 2.91E+00 TCID50/mL
  • hMPV-B1: 2.25E+00 TCID50/mL
  • hMPV-B2: 2.25E+00 TCID50/mL

Analytical Performance: Carryover and Cross-contamination Studies

• Study Type: Internal study
• Key Results: There was no evidence of carry-over/cross contamination on the OuantStudio Dx thermocycler platform when the Quidel Molecular RSV + hMPV Assay was used to detect the presence of high concentrations of RSV-B and hMPV-A1.

Analytical Performance: Competitive Interference

• Study Type: Interference study
• Key Results: At 2X LoD, hMPV was inhibited at a level 10,000X above LoD of RSV-A when tested on the QuantStudio Dx. Inhibition was also seen at this concentration on the Applied Biosystems 7500 Fast Dx and Cepheid SmartCycler II (K122189).

Clinical Performance

• Study Type: Prospective study during the 2013 respiratory virus season (January to March 2013).
• Sample Size: Initial total of 713 nasal or nasopharyngeal swab specimens.
  • For RSV, 13 invalid specimens were removed, resulting in 700 analyzed specimens.
  • For hMPV, 6 invalid specimens were removed, resulting in 707 analyzed specimens.
• Data Source: Nasal or nasopharyngeal swab specimens collected and extracted fresh for routine respiratory virus testing from three sites across the United States.
• Key Results:
  • RSV Performance Comparison:
    • Positive Percent Agreement: 105/112 = 93.8% (95% CI: 87.7% to 96.9%)
    • Negative Percent Agreement: 577/588 = 98.1% (95% CI: 96.7% to 99.0%)
  • hMPV Performance Comparison:
    • Positive Percent Agreement: 55/56 = 98.2% (95% CI: 90.6% to 99.7%)
    • Negative Percent Agreement: 647/651 = 99.4% (95% CI: 98.4% to 99.8%)

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

• RSV:
  • Positive Percent Agreement: 93.8% (95% CI: 87.7% to 96.9%)
  • Negative Percent Agreement: 98.1% (95% CI: 96.7% to 99.0%)
• hMPV:
  • Positive Percent Agreement: 98.2% (95% CI: 90.6% to 99.7%)
  • Negative Percent Agreement: 99.4% (95% CI: 98.4% to 99.8%)

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.

K092500, K082688

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.

K122189

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

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K131813

. . .

Page 1 of 12

510(k) Summary

Applicant:

Quidel Corporation 10165 McKellar Court San Diego. California 92121 Telephone: [phone] Fax: [phone]

Contact Information:

Ronald H. Lollar. Senior Director Clinical and Quality Affairs 1055 East State Street Suite 100 Athens, Ohio 45701 740-589-3300 - Corporate number 740-589-3373 - Desk phone . [phone] - Fax [e-mail]

SEP 06 2013

Date of preparation of 510(k) summary:

June 11, 2013

Device Name:

Trade name - Quidel Molecular RSV + hMPV Assay Classification name - Respiratory viral panel multiplex nucleic acid assay Product Code - OEM, OCC Regulation - 21 CFR 866.3980 Classification - Class II

Device Description:

The Quidel Molecular RSV + hMPV Assay detects viral nucleic acids that have been extracted from a patient sample using the bioMérieux NucliSENS easyMAG automated extraction platform. A multiplex 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 Cepheid SmartCycler II, the Applied Biosystems 7500 Fast Dx. or the Life Technologies QuantStudio Dx. Identification of RSV, hMPV, and the process control (PRC) occurs by the use of target-specific primers and fluorescent-labeled probes that hybridize to conserved regions in the genomes of RSV and hMPV and the PRC.

The following is a summary of the procedure:

1

• Sample Collection: Obtain nasal or nasopharyngeal swab specimens using | . standard techniques from symptomatic patients. Transport, store, and process these specimens according to established laboratory procedures.
• 2. Nucleic Acid Extraction: Extract nucleic acids from the specimens with the BioMérieux NucliSENS easyMAG System following the manufacturer's instructions and using the appropriate reagents.

Prior to the extraction procedure. add 20 uL of the 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 confirms that the nucleic acid extraction was sufficient.

• 3. Rehydration of Master Mix: Rehydrate the lyophilized Master Mix using the Rehydration Solution. The Master Mix contains oligonucleotide primers and fluorophore/quencher-labeled probes that target conserved regions of RSV and hMPV. as well as the PRC.
• 4. Nucleic Acid Amplification and Detection: Add 15 uL of the rehydrated Master Mix to each reaction tube or plate well. Then add 5 µL of extracted nucleic acids (specimen with PRC) to the plate well or appropriately labeled reaction tube. Place the tube or plate into the SmartCycler II, 7500 Fast Dx, or the Life Technologies QuantStudio Dx instruments.

Once the reaction tube or plate is added to the instrument, initiate the assay protocol. This protocol initiates reverse transcription of the RNA targets. generating complementary DNA and the subsequent amplification of the target amplicons. The Quidel Molecular RSV + hMPV Assay is based on TagMan 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 fluorescence is achieved, the sample is reported as positive for the detected nucleic acid.

Intended Use:

The Quidel Molecular RSV + hMPV Assay is a multiplex Real-Time PCR (RT-PCR) assay for the qualitative detection and identification of respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) ribonucleic acid (RNA) extracted from nasal and nasopharyngeal swab specimens from patients with signs and symptoms of respiratory infection. This in vitro diagnostic test is intended to

2

aid in the differential diagnosis of RSV and hMPV infections in humans in conjunction with clinical and epidemiological risk factors. This test is not intended to differentiate the two subtypes of RSV or the four genetic sub-lineages of hMPV.

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

Conversely, 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 and clinical presentation must be considered in order to obtain the final diagnosis of respiratory viral infection.

The Quidel Molecular RSV + hMPV Assay can be performed using either the Life Technologies QuantStudio" Dx RT-PCR Instrument, the Applied Biosystems® 7500 Fast Dx RT-PCR Instrument, or the Cepheid SmartCycler® II System.

Conditions for Use:

For prescription use only.

Device Comparison

The Quidel Molecular RSV + hMPV Assay was compared to two FDA cleared RT-PCR assays. The characteristics of Quidel Molecular RSV + hMPV Assay ("Subject Device") and the Prodesse ProFlu + and Pro hMPV+ ("Predicate Devices") are described in the table below:

Subject Device and Comparator Device Comparison
Item	Subject Device
Quidel Molecular
RSV + hMPV Assay	Predicate Device
Prodesse ProFlu+
(K092500)	Predicate Device
Prodesse Pro hMPV+
(K082688)
Intended Use	The Quidel
Molecular RSV +
hMPV Assay is a
multiplex Real-Time
PCR (RT-PCR)
assay for the
qualitative detection
and identification of
respiratory syncytial	The ProFlu TM+ 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	The Pro hMPV+
Assay is a Real-Time
RT-PCR in vitro
diagnostic test for the
qualitative detection
of human
Metapneumovirus
(hMPV) nucleic acid
isolated and purified
from nasopharyngeal
swab (NP) specimens
Subject Device and Comparator Device Comparison
Item	Subject Device
Quidel Molecular
RSV + hMPV Assay	Predicate Device
Prodesse ProFlu+
(K092500)	Predicate Device
Prodesse Pro hMPV+
(K082688)
	virus (RSV) and
human
metapneumovirus
(hMPV) ribonucleic
acid (RNA)
extracted from nasal
and nasopharyngeal
swab specimens
from patients with
signs and symptoms
of respiratory
infection. This in
vitro diagnostic test
is intended to aid in
the differential
diagnosis of RSV
and hMPV
infections in humans
in conjunction with
clinical and
epidemiological risk
factors. This test is
not intended to
differentiate the two
subtypes of RSV or
the four genetic sub-
lineages of hMPV.

Negative results do
not preclude RSV
infection and/or
hMPV infection and
should not be used
as the sole basis for
diagnosis, treatment
or other patient
management | (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.

Negative results do
not preclude
influenza or RSV
virus infection and
should not be used as
the sole basis for
treatment or other
management
decisions.
Conversely, 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 and
clinical presentation
must be considered in
order to obtain the
final diagnosis of
respiratory viral
infection. | obtained from
individuals exhibiting
signs and symptoms
of acute respiratory
infection. This assay
targets a highly
conserved region of
the Nucleocapsid
gene of hMPV. The
detection of hMPV
nucleic acid from
symptomatic patients
aids in the diagnosis
of human respiratory
hMPV infection if
used in conjunction
with other clinical
and laboratory
findings. This test is
not intended to
differentiate the four
genetic sub-lineages
of hMPV.

Negative results do
not preclude hMPV
infection and should
not be used as the
sole basis for
diagnosis, treatment
or other management
decisions. |
| Subject Device and Comparator Device Comparison | | | |
| Item | Subject Device
Quidel Molecular
RSV + hMPV Assay | Predicate Device
Prodesse ProFlu+
(K092500) | Predicate Device
Prodesse Pro hMPV+
(K082688) |
| | decisions.
Conversely, 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 and clinical
presentation must be
considered in order
to obtain the final
diagnosis of
respiratory viral
infection.
The Quidel
Molecular RSV +
hMPV Assay can be
performed using the
Life Technologies
QuantStudioTM Dx
RT-PCR Instrument,
the Applied
Biosystems® 7500
Fast Dx RT-PCR
Instrument, or the
Cepheid
SmartCycler® II
System. | Performance
characteristics for
Influenza A Virus
were established
when Influenza A/H3
and A/H1 were the
predominant
Influenza A viruses
in circulation (2006-
2007 respiratory
season). Performance
characteristics for
Influenza A were
confirmed when
Influenza A/H1,
Influenza A/H3, and
Influenza A/2009
HiNi were the
predominant
Influenza A viruses
in circulation (2008
and 2009). 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 | |
| Subject Device and Comparator Device Comparison | | | |
| Item | Subject Device
Quidel Molecular
RSV + hMPV Assay | Predicate Device
Prodesse ProFlu+
(K092500) | Predicate Device
Prodesse Pro hMPV+
(K082688) |
| | | 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. | |
| Assay Target | RSV, hMPV | Influenza A virus,
influenza B virus,
RSV | hMPV |
| Sample Types | Nasal swab,
nasopharyngeal
swab | Nasopharyngeal swab | Nasopharyngeal swab |
| Instrument/Assay
Platform | Life Technologies
QuantStudio Dx RT-
PCR Instrument, the
Applied Biosystems
7500 Fast Dx RT-
PCR Instrument, or
the Cepheid
SmartCycler II
System | Cepheid SmartCycler
II System | Cepheid SmartCycler
II System |
| Assay Controls | An internal RNA
control is provided | Influenza A,
Influenza B, RSV A,
RSV B positive RNA
transcript controls
and an internal RNA
control are provided | hMPV positive RNA
transcript control and
an internal RNA
control are provided |
| Extraction
Methods | bioMérieux
NucliSENS
easyMAG System | Roche MagNA Pure
LC Total Nucleic
Acid Isolation Kit or | Roche MagNA Pure
LC Total Nucleic
Acid Isolation Kit or |
| Subject Device and Comparator Device Comparison | | | |
| Item | Subject Device
Quidel Molecular
RSV + hMPV Assay | Predicate Device
Prodesse ProFlu+
(K092500) | Predicate Device
Prodesse Pro hMPV+
(K082688) |
| | | the bioMérieux
NucliSENS
easyMAG System | the bioMérieux
NucliSENS
easyMAG System |
| Assay
Methodology | RT-PCR-based
system for detecting
the presence or
absence of viral
RNA in clinical
specimens | RT-PCR-based
system for detecting
the presence or
absence of viral RNA
in clinical specimens | RT-PCR-based
system for detecting
the presence or
absence of viral RNA
in clinical specimens |
| Viral Targets | RSV: L viral
polymerase and NS2
genes
hMPV: RNA
polymerase gene | Influenza A: Matrix
Gene;
Influenza B: Non-
structural NS1 and
NS2
RSV A and RSV B:
polymerase | Nucleocapsid gene |

3

4

.

.

5

.

6

Analytical Performance:

Reproducibility:

The reproducibility of the Quidel Molecular RSV + hMPV Assay using the Life Technologies QuantStudio Dx Real-Time PCR Instrument was evaluated at 3 laboratory sites (two external, one in-house). Reproducibility was assessed using a panel of 4 simulated samples that include medium positive, low positive, high negative, and negative samples. Separate panels were constructed for RSV and hMPV, using the RSV-A Long strain and hMPV-A2 strain respectively. Panels and controls were extracted using the bioMérieux NucliSENS easyMAG System and 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 LoD values are based on the values obtained in the LoD study.

Reproducibility Results – QuantStudio Dx
Panel
Member
ID	Site 1			Site 2			Site 3			Total
Results
	Results	AVE
Ct	%CV	Results	AVE
Ct	%CV	Results	AVE
Ct	%CV
RSV
High
Negative
0.3x	15/30	37.6	3.7	1/30	37.7	N/A	23/30	36.7	3.7	39/90
Reproducibility Results -QuantStudio Dx
Panel
Member
ID	Site 1			Site 2			Site 3			Total
Results
LoD	Results	AVE
Ct	%CV	Results	AVE
Ct	%CV	Results	AVE
Ct	%CV
RSV
Low
Positive
2x LoD	30/30	32.3	5.3	29/30	34.9	5.0	30/30	32.1	2.7	89/90
RSV
Med
Positive
5x LoD	30/30	30.3	1.9	30/30	31.5	5.5	30/30	29.9	1.6	90/90
RSV
Negative	0/30	N/A	N/A	0/30	N/A	N/A	0/30	N/A	N/A	0/90
RSV
Negative
Control	0/30	N/A	N/A	0/30	N/A	N/A	0/30	N/A	N/A	0/90
RSV
Positive
Control	30/30	30.9	1.7	30/30	33.0	5.1	30/30	31.9	10.2	90/90
hMPV
High
Negative
0.15x
LoD	20/30	35.9	4.0	11/30	35.2	5.9	21/30	36.6	4.0	52/90
hMPV
Low
Positive
2x LoD	30/30	30.3	5.0	30/30	30.2	2.5	30/30	30.4	2.1	90/90
hMPV
Med
Positive
5x LoD	30/30	28.9	2.0	30/30	28.4	1.2	30/30	28.3	3.7	90/90
hMPV
Negative	0/30	N/A	N/A	0/30	N/A	N/A	0/30	N/A	N/A	0/90
hMPV
Negative	0/30	N/A	N/A	0/30	N/A	N/A	0/30	N/A	N/A	0/90
Reproducibility Results -QuantStudio Dx
Panel
Member
ID	Site 1			Site 2			Site 3			Total
Results
	Results	AVE
Ct	%CV	Results	AVE
Ct	%CV	Results	AVE
Ct	%CV
Control
hMPV
Positive
Control	30/30	28.7	0.6	30/30	28.1	2.3	30/30	28.3	4.4	90/90

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The data from the combined sites indicates that the Quidel Molecular RSV + hMPV Assay generates reproducible results for RSV and hMPV when tested with the Life Technologies QuantStudio Dx.

Combined Sites RSV
	5X LoD	2X LoD	0.3X LoD	Negative	Positive
Control	Negative
Control
Detection %	100%	98.9%	43.3%	0%	100%	0%
Ave.	30.6	33.1	37.1	N/A	31.9	N/A
STDEV	1.3	1.9	1.4	N/A	2.3	N/A
%CV	4%	6%	4%	N/A	7%	N/A

	Combined Sites hMPV
	5X LoD	2X LoD	0.15X LoD	Negative	Positive
Control	Negative
Control
Detection %	100%	100%	57.8%	0%	100%	0%
Ave.	28.6	30.3	36.0	N/A	28.3	N/A
STDEV	0.8	1.0	1.6	N/A	0.8	N/A
%CV	3%	3%	4%	N/A	3.0%	N/A

Precision

The precision of the Quidel Molecular RSV + hMPV Assay using the Life Technologies QuantStudio Dx Real-Time PCR Instrument was determined using quantified dilutions of RSV and hMPV stocks (10X, 3X, and 0.15X LoD). These dilutions were tested by two operators for twelve days. The data from this study indicates that when tested on the Life Technologies QuantStudio Dx Real-Time PCR Instrument, the Quidel Molecular RSV + hMPV Assay produces repeatable, precise results.

Limit of Detection

The analytical sensitivity (limit of detection or LoD) of the Quidel Molecular RSV + hMPV Assay using the Life Technologies QuantStudio Dx Real-Time PCR Instrument was determined using quantified (TCID50mL) cultures of 2 RSV strains (RSV-A Long

9

and RSV-B Washington strains) and 4 hMPV strains (hMPV A1, hMPV A2, hMPV B1, and hMPV B2 strains) serially diluted in negative nasal matrix. Each dilution was extracted in replicates of 20 per concentration of virus using the bioMérieux NucliSENS easyMAG System. Analytical sensitivity (LoD) is defined as the lowest concentration at which 95% of all replicates tested positive.

| Virus | LoD TCID50/mL
QuantStudio Dx |
|---------|---------------------------------|
| RSV A | 6.29E-01 |
| RSV B | 2.25E-01 |
| hMPV-A1 | 8.73E+00 |
| hMPV-A2 | 2.91E+00 |
| hMPV-B1 | 2.25E+00 |
| hMPV-B2 | 2.25E+00 |

Carryover and Cross-contamination Studies

In an internal study there was no evidence of carry-over/cross contamination on the OuantStudio Dx thermocycler platform when the Quidel Molecular RSV + hMPV Assay was used to detect the presence of high concentrations of RSV-B and hMPV-A1 (2.57E+06 and 3.16E+07. respectively) extracted with the BioMérieux NucliSENS easyMAG System.

Competitive Interference

A study was performed to determine whether competitive interference exists when both RSV and hMPV analytes are present in the same reaction when tested on the Life Technologies OuantStudio Dx Real-Time PCR Instrument. Results showed that at 2X LoD hMPV was inhibited at a level 10,000X above LoD of RSV-A when tested on the QuantStudio Dx. Inhibition was also seen at this concentration on the Applied Biosystems 7500 Fast Dx and Cepheid SmartCycler II (K122189).

Analytical Reactivity (Inclusivity):

Please see K122189 for Analytical Reactivity (Inclusivity) studies.

Analytical Specificity (Cross-Reactivity):

Please see K122189 for Analytical Specificity (Cross-Reactivity) studies.

Clinical Performance:

Performance characteristics of the Quidel Molecular RSV + hMPV Assay using the Life Technologies QuantStudio Dx Real-Time PCR Instrument was established during a prospective study during the 2013 respiratory virus season (January to March 2013). Seven hundred and thirteen (713) nasal or nasopharyngeal swab specimens that were collected and extracted fresh for routine respiratory virus testing were used for this study at three (3) sites across the United States. A single specimen was collected per patient.

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The specimens were extracted with the bioMérieux NucliSENS easyMAG System and tested with the Quidel Molecular RSV + hMPV Assay using the Life Technologies QuantStudio Dx RT-PCR Instrument. Sites 1 and 2 also extracted each specimen with the bioMérieux NucliSENS easyMAG System and tested with the comparator devices. Aliquots of each specimen from Site 3 were sent to Site 1 for testing with the comparator devices. Sample extracts were stored at -70℃ until the time of testing.

Combined Clinical Site Data:

Seven hundred and thirteen (713) nasal or nasopharyngeal swab specimens were tested by both the subject and comparator device for RSV viral RNA. A total of thirteen (13) invalid specimens were removed from the analysis. Two (2) of these specimens were invalid on initial and repeat testing with the subject device (0.3%). Eleven (11) specimens were invalid on initial and repeat testing on the comparator device (1.5%). The table below details the results for the remaining seven hundred (700) specimens.

RSV
	Comparator: FDA Cleared RT-PCR device
Quidel Molecular	Positive	Negative	Total
Positive	105	11	116
Negative	7	577	584
Total	112	588	700
			95% CI
Positive Percent Agreement	105/112	93.8%	87.7% to 96.9%
Negative Percent Agreement	577/588	98.1%	96.7% to 99.0%

Seven hundred and thirteen (713) nasal or nasopharyngeal swab specimens were tested by both the subject and comparator device for hMPV viral RNA. A total of six (6) invalid specimens were removed from the analysis. Two (2) of these specimens were invalid on initial and repeat testing with the subject device (0.3%). Four (4) specimens were invalid on initial and repeat testing on the comparator device (0.6%). The table below details the results for the remaining seven hundred and seven (707) specimens.

hMPV
	Comparator: FDA Cleared RT-PCR device
Quidel Molecular	Positive	Negative	Total
Positive	55	4	59
Negative	1	647	648
Total	56	651	707
95% CI
Positive Percent Agreement	55/56	98.2%	90.6% to 99.7%
Negative Percent Agreement	647/651	99.4%	98.4% to 99.8%

Conclusions:

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The results of the analytical and clinical performance studies submitted in this premarket notification are complete and demonstrate that, when performed on the Life Technologies QuantStudio Dx RT-PCR Instrument, the Quidel Molecular RSV + hMPV Assay was substantially equivalent compared to the two FDA 510(k) cleared molecular devices.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/12/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized depiction of an abstract caduceus, which is a symbol often associated with healthcare and medicine. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular fashion around the symbol.

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-C609 Silver Spring, MI) 20993-0002

September 6, 2013

QUIDEL CORPORATION C/O RONALD H. LOLLAR SENIOR DIRECTOR CLINICAL AND QUALITY AFFAIRS DIAGNOSTIC HYBRIDS, INC. 1055 EAST STATE STREET. SUITE 100 ATHENS OH 45701

Rc: K131813

Trade/Device Name: Ouidel Molecular RSV + hMPV Assay Regulation Number: 21 CFR 866.3980 Regulation Name: Respiratory viral panel multiplex nucleic acid assay Regulatory Class: II Product Code: OEM. OCC Dated: June 19. 2013 Received: June 20, 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 10 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. Please note: CDRFI 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 Parts 801 and 809): medical device 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.

13

Page 2-Mr. Lollar

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/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 [phone] or [phone] or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.

Sincerely yours,

Sally A. Hojvat -S

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

Enclosure

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Indications for Use

510(k) Number: K131813

Device Name: Quidel Molecular RSV + hMPV Assay

Indications for Use:

The Quidel Molecular RSV + hMPV Assay is a multiplex Real-Time PCR (RT-PCR) assay for the qualitative detection and identification of respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) ribonucleic acid (RNA) extracted from nasal and nasopharyngeal swab specimens from patients with signs and symptoms of respiratory infection. This in vitro diagnostic test is intended to aid in the differential diagnosis of RSV and hMPV infections in humans in conjunction with clinical and epidemiological risk factors. This test is not intended to differentiate the two subtypes of RSV or the four genetic sub-lineages of hMPV.

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

Conversely, 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 and clinical presentation must be considered in order to obtain the final diagnosis of respiratory viral infection.

The Quidel Molecular RSV + hMPV Assay can be performed using either the Life Technologies QuantStudio™ Dx RT-PCR Instrument, the Applied Biosystems® 7500 Fast Dx RT-PCR Instrument, or the Cepheid SmartCycler® II System.

Prescription Use __________________________________________________________________________________________________________________(21 CFR 801 Subpa (21 CFR 801 Subpart C)

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

Concurrence of Center for Devices and Radiological Health (CDRH)

Tamara V. Feldblyum -S 2013.09.04 16:11:21 -04'00'