Predicate Devices

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The device description details a process involving nucleic acid extraction, RT-PCR, mass spectrometry, and comparison to a proprietary database. There is no mention of AI, ML, or related concepts in the device description, intended use, or performance studies. The data analysis is described as a comparison to a database, which is a standard computational process, not necessarily AI/ML.

Therapeutic

No
The device is an in vitro diagnostic test for detecting influenza viral nucleic acids, which aids in diagnosis rather than providing therapy.

Diagnostic

Yes

Explanation: The "Intended Use / Indications for Use" section explicitly states that the PLEX-ID Flu assay is "a qualitative nucleic acid in vitro diagnostic test" and is intended "as an aid in the diagnosis of influenza infection."

SaMD (Software as a Medical Device)

No

The device description explicitly states that the assay involves physical kits (PLEX-ID Flu Amplification Kit and Control Kit) and requires analysis on the PLEX-ID Analyzer, which is a mass spectrometer. This indicates the device includes hardware components and is not software-only.

IVD (In Vitro Diagnostic)

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

The "Intended Use / Indications for Use" section explicitly states: "The PLEX-ID Flu assay is a qualitative nucleic acid in vitro diagnostic test intended for the detection and differentiation of influenza A HINI (2009), influenza A H1N1 (seasonal), influenza A H3N2 (seasonal) and influenza B viral nucleic acids in nasopharyngeal swab specimens from patients symptomatic for respiratory tract infection."

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 PLEX-ID Flu assay is a qualitative nucleic acid in vitro diagnostic test intended for the detection and differentiation of influenza A H1N1 (2009), influenza A H1N1 (seasonal), influenza A H3N2 (seasonal) and influenza B viral nucleic acids in nasopharyngeal swab specimens from patients symptomatic for respiratory tract infection. The PLEX-ID Flu assay is intended for use on the PLEX-ID System (version 1.2) as an aid in the diagnosis of influenza infection in conjunction with clinical and epidemiological information. This assay is not intended to detect 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.

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 departments 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

OCC, OEP, OQW, OTA

Device Description

The PLEX-ID Flu assay consists of the following kits:

PLEX-ID Flu Amplification Kit (List No. 05N21-91)
PLEX-ID Flu Control Kit (List No. 05N21-80)

The PLEX-ID Flu assay is a qualitative in vitro diagnostic test used for the detection and identification of influenza A and B viruses directly from human samples. First, nucleic acids are extracted from samples. Nucleic acids are then amplified via a reverse transcription polymerase chain reaction (RT-PCR). The PCR products are subsequently desalted and analyzed in a mass spectrometer to determine the base composition of the PCR products. Analysis of the base composition of PCR products is used to determine identity by comparison to a proprietary database. Desalting, mass spectrometry and data analysis are conducted on the PLEX-ID Analyzer. Reported results include an identification of influenza virus species and subtypes of influenza A virus.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

nasopharyngeal swab specimens / nasopharyngeal (NP) swab specimens

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

A total of 1287 prospective NP swab specimens were collected for the PLEX-ID Flu clinical study. Of the 1287, five specimens were excluded: duplicate specimens were collected from two subjects (the second specimen from each subject was excluded from the analysis), one specimen from a subject who did not meet the inclusion criteria, and two specimens had an invalid PLEX-ID Flu result, for a total of 1282 included specimens. The specimens were collected from two U.S. clinical sites and three specimen suppliers from September 2009 through June 2010.

A total of 1378 retrospective specimens were tested. Of these specimens, 1341 were included in the analysis (the remaining 37 were excluded either due to unavailable results for the PLEX-ID Flu assay or Comparator 1 assay, duplicate subjects, or failure to meet subject inclusion criteria). These specimens consisted of pre-selected banked specimens collected in February 2008, and from January 2009 through March 2009, and left over archived specimens collected from April 2009 through December 2009.

Clinical performance was assessed by testing nasopharyngeal (NP) swab specimens from subjects presenting with symptoms of influenza-like illness. Prospectively collected clinical specimens were tested at three sites. All specimens were tested with an assay FDA cleared for the detection and discrimination of influenza A virus, influenza B virus, and Respiratory Syncytial virus nucleic acids isolated and purified from NP swab specimens obtained from symptomatic patients (Comparator 1). Specimens with a positive influenza A test result went on for further testing with Comparator 2, an assay FDA cleared for the detection and discrimination of influenza A virus subtypes [influenza A HINI (2009), influenza A H1NI (seasonal), influenza A H3N2 (seasonal)] from nucleic acids isolated and purified from NP swab specimens. Aliquots from the same specimens were tested with the PLEX-ID Flu assay. PCR followed by bi-directional sequencing was used to test discrepant samples between Comparator 1 and Comparator 2, Comparator 1 vs. PLEX-ID Flu, and Comparator 2 vs. PLEX-ID Flu. The results from bi-directional sequence testing were not used to calculate the positive percent agreement and negative percent agreement of the PLEX-ID Flu assay.

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

Clinical Performance - Prospective Clinical Study

Sample size: 1276
Key Results:
- Influenza A H1N1 (2009) Specimen Testing:
  - Positive Percent Agreement: 100.0% (32/32) (95% CI: 89.3%, 100.0%)
  - Negative Percent Agreement: 99.6% (1239/1244) (95% CI: 99.1%, 99.8%)
- Influenza A H1N1 (Seasonal) Specimen Testing:
  - Positive Percent Agreement: 57.1% (4/7) (95% CI: 25.0%, 84.2%)
  - Negative Percent Agreement: 100.0% (1269/1269) (95% CI: 99.7%, 100.0%)
- Influenza A H3N2 (Seasonal) Specimen Testing:
  - Positive Percent Agreement: 98.0% (48/49) (95% CI: 89.3%, 99.6%)
  - Negative Percent Agreement: 99.8% (1225/1227) (95% CI: 99.4%, 100.0%)
- Influenza B Specimen Testing:
  - Positive Percent Agreement: 100.0% (22/22) (95% CI: 85.1%, 100.0%)
  - Negative Percent Agreement: 99.8% (1252/1254) (95% CI: 99.4%, 100.0%)

Clinical Performance - Retrospective Specimen Testing

Sample size: 1339 or 1341 (depending on specific comparison)
Key Results:
- Influenza A H1N1 (2009) Specimen Testing:
  - Positive Percent Agreement: 98.2% (538/548) (95% CI: 96.7%, 99.0%)
  - Negative Percent Agreement: 94.3% (746/791) (95% CI: 92.5%, 95.7%)
- Influenza A H1N1 (Seasonal) Specimen Testing:
  - Positive Percent Agreement: 96.4% (27/28) (95% CI: 82.3%, 99.4%)
  - Negative Percent Agreement: 100.0% (1311/1311) (95% CI: 99.7%, 100.0%)
- Influenza A H3N2 (Seasonal) Specimen Testing:
  - Positive Percent Agreement: 100.0% (2/2) (95% CI: 34.2%, 100.0%)
  - Negative Percent Agreement: 100.0% (1337/1337) (95% CI: 99.7%, 100.0%)
- Influenza B Specimen Testing:
  - Positive Percent Agreement: 92.9% (26/28) (95% CI: 77.4%, 98.0%)
  - Negative Percent Agreement: 99.9% (1312/1313) (95% CI: 99.6%, 100.0%)

Limit of Detection (LOD) Study

Study type: Laboratory testing of quantitated influenza strains diluted in negative nasopharyngeal swab matrix.
Sample size: 20 replicates for each influenza strain.
Key Results:
- influenza A H1N1 (2009): 1.3 × 101 TCID50/mL
- influenza A H1N1 (seasonal): 4.6 × 100 TCID50/mL
- influenza A H3N2 (seasonal): 3.3 × 102 TCID50/mL
- influenza B: 1.5 × 101 TCID50/mL

Reproducibility Study

Study type: Multi-site evaluation of a nine-member panel of contrived samples.
Sample size: A total of 120 results for each panel member over 5 days of testing (replicates of 4, 2 batches per day, 2 operators per site).
Key Results (Total of All Sites):
- Negative: 120/120 (100.0%) (95% CI: 96.9%, 100.0%)
- influenza A H1N1 (2009) Low Positive: 117/119 (98.3%) (95% CI: 94.1%, 99.5%)
- influenza A H1N1 (2009) Moderate Positive: 120/120 (100.0%) (95% CI: 96.9%, 100.0%)
- influenza A H1N1 (seasonal) Low Positive: 118/120 (98.3%) (95% CI: 94.1%, 99.5%)
- influenza A H1N1 (seasonal) Moderate Positive: 120/120 (100.0%) (95% CI: 96.9%, 100.0%)
- influenza A H3N2 (seasonal) Low Positive: 119/119 (100.0%) (95% CI: 96.9%, 100.0%)
- influenza A H3N2 (seasonal) Moderate Positive: 119/120 (99.2%) (95% CI: 95.4%, 99.9%)
- influenza B Low Positive: 118/119 (99.2%) (95% CI: 95.4%, 99.9%)
- influenza B Moderate Positive: 119/120 (99.2%) (95% CI: 95.4%, 99.9%)

Within Laboratory Precision Study

Study type: Testing of nine members of a reproducibility panel in duplicate in two runs per day for twelve days.
Sample size: 48 replicates for each panel member.
Key Results: All nine panel members showed 100% agreement (48/48) with 95% Confidence Interval of (93%, 100%).

Cross-Reactivity Study

Study type: Evaluation of 34 common respiratory microbes.
Key Results: No interference observed in the performance of the PLEX-ID Flu assay in the presence of the potential cross-reactants for all positive and negative samples tested.

Potentially Interfering Substances Study

Study type: Evaluation of substances that may be present in nasopharyngeal swab samples.
Key Results: No interference observed in the performance of the PLEX-ID Flu assay for all positive and negative samples tested, except for FluMist® which may cause false positive results.

Carryover Study

Study type: Evaluation of sample carryover using high target concentrations of influenza A and B alternately loaded with negative samples.
Sample size: 120 negative samples.
Key Results: Observed carryover rate of 0% (0/120).

Inclusivity Study

Study type: Testing of multiple viral strains representing temporal and geographical diversity.
Key Results: The results reported for each strain tested matched the expected result in 3 out of 3 replicates.

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

Positive Percent Agreement (PPA) / Sensitivity:
- Prospective Study:
  - H1N1 (2009): 100.0%
  - H1N1 (Seasonal): 57.1%
  - H3N2 (Seasonal): 98.0%
  - Influenza B: 100.0%
- Retrospective Study:
  - H1N1 (2009): 98.2%
  - H1N1 (Seasonal): 96.4%
  - H3N2 (Seasonal): 100.0%
  - Influenza B: 92.9%
Negative Percent Agreement (NPA) / Specificity:
- Prospective Study:
  - H1N1 (2009): 99.6%
  - H1N1 (Seasonal): 100.0%
  - H3N2 (Seasonal): 99.8%
  - Influenza B: 99.8%
- Retrospective Study:
  - H1N1 (2009): 94.3%
  - H1N1 (Seasonal): 100.0%
  - H3N2 (Seasonal): 100.0%
  - Influenza B: 99.9%

Predicate Device(s)

K073029, K101855

Reference Device(s)

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information

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

5.0 510(k) Summary

510(k) Number: K121003

Device Name: PLEX-ID Flu

Purpose of the Submission: The purpose of this 510(k) is to gain clearance to market the PLEX-ID Flu (List No. 05N21) assay.

5.1 Official Correspondent to the File

Darren Clarke Name Director Regulatory Affairs Title: Telephone: (760) 476-3224 Fax: (760) 476-3301 Email: darren.clarke@abbott.com

Name Samuel Mathew Title: Associate Director of Regulatory Affairs Telephone: (224) 361-7062 Fax: (847) 775-6777 Email: samuel.mathew@abbott.com

Address: Abbott Molecular Inc. 1300 E. Touhy Avenue Des Plaines, IL 60018

5.2 Date of Preparation

March 30, 2012

5.3 Sponsor

Abbott Molecular Inc. is sponsor of the PLEX-ID Flu (List No. 05N21) 510(k) submission.

5.4 Intended Use

The PLEX-ID Flu assay is a qualitative nucleic acid in vitro diagnostic test intended for the detection and differentiation of influenza A HINI (2009), influenza A H1N1 (seasonal), influenza A H3N2 (seasonal) and influenza B viral nucleic acids in nasopharyngeal swab specimens from patients symptomatic for respiratory tract infection. The PLEX-ID Flu assay is intended for use on the PLEX-ID System (version 1.2) as an aid in the diagnosis of influenza infection in conjunction with clinical and epidemiological information. This assay is not intended to detect influenza C virus.

PLEX-ID Flu 510(k) K121003 December 2012

510(k) Summary Page 1 of 31

DEC 2 1 2012

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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,

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 departments for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.

ર્સ્ડ Trade Name

PLEX-ID Flu (List No. 05N21)

5.6 Common Name

Nucleic acid assay for the detection of influenza virus

5.7 Classification Name and Regulation

. Regulation Number: 21 CFR 866.3980
Classification Name: Respiratory viral panel multiplex nucleic acid assay .

5.8 Predicate Devices

Prodesse ProFLU+ TM assay (K073029) .
Prodesse ProFAST+ TM assay (K101855) .

2

5.9 Device Description

The PLEX-ID Flu assay consists of the following kits:

. PLEX-ID Flu Amplification Kit (List No. 05N21-91)
. PLEX-ID Flu Control Kit (List No. 05N21-80)

The PLEX-ID Flu assay is a qualitative in vitro diagnostic test used for the detection and identification of influenza A and B viruses directly from human samples. First, nucleic acids are extracted from samples. Nucleic acids are then amplified via a reverse transcription polymerase chain reaction (RT-PCR). The PCR products are subsequently desalted and analyzed in a mass spectrometer to determine the base composition of the PCR products. Analysis of the base composition of PCR products is used to determine identity by comparison to a proprietary database. Desalting, mass spectrometry and data analysis are conducted on the PLEX-ID Analyzer. Reported results include an identification of influenza virus species and subtypes of influenza A virus.

5.10 Background on Influenza

Influenza is a respiratory virus that can cause mild to severe disease, and at times can lead to death. Every year in the United States, on average 5% to 20% of the population gets the flu; more than 200,000 people are hospitalized from flu complications, and about 3,000 to 49,000 people die from flu-related causes. Some people, such as adults 65 years or older, young children, and people with certain health conditions, are at high risk for serious flu complications.1,2

There are two main types of influenza (flu) virus, A and B, which are responsible for seasonal epidemics of flu amongst humans. Influenza A viruses are divided into subtypes based on two proteins on the surface of the virus: hemagglutinin (H) and neuraminidase (N). The common Influenza A virus subtypes found in people are A (HINI) and A (H3N2). In April of 2009, a new strain of Influenza A emerged. On June 11, 2009 WHO classified the 2009 H1N1 Influenza A strain as the cause of a phase 6 pandemic.3

PLEX-ID Flu 510(k) K121003 December 2012

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5.11 Technological Characteristics of the Device as Compared to the Predicate

These devices are similar in that they are designed to prepare nucleic acids for amplification, amplify specific influenza sequences, detect the amplified products, and report qualitative results.

The primary similarities and differences between the PLEX-ID Flu assay and the predicate devices are shown in Table 1.

4

Table 1

Similarities and Differences Between PLEX-ID Flu and Predicate Device

Current Application	Predicate Devices	Feature	Current Application	Predicate Devices
PLEX-ID Flu	Prodesse ProFLU+	Prodesse ProFAST+	Assay Type	PLEX-ID Flu	Prodesse ProFLU+	Prodesse ProFAST+
K121003	K073029	K101855	Analyte Targets	Qualitative influenza genus→ Primer pair 2798 targets polymerase PB1 influenza A → Primer Pair 1266 targets nucleoprotein influenza A → Primer Pair 1279 targets matrix protein influenza A → Primer Pair 1287 polymerase A protein influenza A → Primer Pair 2775 non-structural protein 1, NS1 influenza A → Primer Pair 1259 targets polymerase, PB influenza A H1N1 (2009) → Primer Pair 5101 targets hemagglutinin, HA influenza A H1N1 (2009) → Primer Pair 4998 targets neuraminidase, NA influenza B→ Primer Pair 1261 targets polymerase, PB2	Qualitative Influenza A Virus → Matrix Respiratory Syncytial Virus A →Polymerase Respiratory Syncytial Virus B →Polymerase Influenza B Virus → Non-structural NS1 and NS2	Qualitative Seasonal H1 Influenza A → Hemagglutinin Seasonal H3 Influenza A → Hemagglutinin 2009 H1N1 Influenza Virus → Hemagglutinin
21 CFR 866.3980
OEP, OCC, OQW, OTA	21 CFR 866.3980
OCC	21 CFR 866.3332
OQW	Input Sample Types	nasopharyngeal swab	nasopharyngeal swab	nasopharyngeal swab
Feature	Current Application	Predicate Devices
Intended Use	PLEX-ID Flu
The PLEX-ID Flu assay is a qualitative nucleic acid in vitro diagnostic test intended for the detection and differentiation of influenza A H1N1 (2009), influenza A H1N1 (seasonal), influenza A H3N2 (seasonal) and influenza B viral nucleic acids in nasopharyngeal swab specimens from patients symptomatic for respiratory tract infection. The PLEX-ID Flu assay is intended for use on the PLEX-ID System (version 1.2) as an aid in the diagnosis of influenza infection in conjunction with clinical and epidemiological information. This assay is not intended to detect 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. 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 departments for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.	Prodesse ProFLU+
The ProFlu™+ 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. 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. It is recommended that negative RSV results be confirmed by 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 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.	Prodesse ProFAST+
The ProFAST™+ Assay is a multiplex Real Time RT-PCR in vitro diagnostic test for the qualitative detection and discrimination of seasonal Influenza A/H1, seasonal Influenza A/H3 and 2009 H1N1 Influenza viral nucleic acids isolated and purified from nasopharyngeal (NP) swab specimens from human patients with signs and symptoms of respiratory infection in conjunction with clinical and epidemiological risk factors. This assay targets conserved regions of the Hemagglutinin (HA) gene for seasonal Influenza A/H1, seasonal Influenza A/H3 and 2009 H1N1 Influenza Virus, respectively. This assay is not intended to detect Influenza B or Influenza C Viruses. A negative ProFAST+ Assay result is a presumptive negative result for Influenza A. These results should be confirmed by an FDA cleared nucleic acid-based test (NAT) detecting Influenza A. Negative results do not preclude Influenza virus infection and should not be used as the sole basis for treatment or other patient management decisions. 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.

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510(k) Summary

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PLEX-ID Flu 510(k) K12
December 2012

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PLEX-ID Flu 510
December 2012

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PLEX-ID (K) KT21003
December 2012

510(k) Summary

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| Feature | Current Application
PLEX-ID Flu | Prodesse ProFLU+ | Predicate Devices
Prodesse ProFAST+ |
|------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Sample
Collection | Immediately following collection of
the sample from the patient, place the
swab into a tube containing 3 mL of
viral transport media. Place on ice or
refrigerate. Samples for the PLEX-ID
Flu assay may be collected in: Micro TestTM M4R Viral
Transport Medium Micro TestTM M5R Viral
Transport Medium Micro TestTM M6R Viral
Transport Medium Micro TestTM M4RTR Viral
Transport Medium Copan Universal Transport
Medium BD Universal Viral Transport
Medium | Following collection, place the swab into
a tube containing 2 to 3 mL of viral
transport medium (Remel M4, M4RT,
M5, M6; Copan UTM; or Becton
Dickenson UVT). | Following collection, place the swab into a
tube containing 2 to 3 mL of viral transport
medium (Remel M4, M4RT, M5, M6; Copan
UTM; or Becton Dickenson UVT). When starting from purified nucleic acid
samples that have been previously processed
for testing with the ProFLU+ Assay, begin
with the RT-PCR reaction. |
| Input Sample
Volume | 300 µL | 180 µL | 180 µL |

PLEX-ID December 2012

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510(k) Summary

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| Feature | Current Application
PLEX-ID Flu | Predicate Devices
Prodesse ProFLU+ | Predicate Devices
Prodesse ProFAST+ | | | |
|------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------|
| Principles
of the
Procedure | Automated sample to extraction plate Automated nucleic acid extraction Automated transfer of sample eluate to PCR Plate Automated PCR amplification Automated desalting of PCR products Mass Spectrometry analysis converts mass of PCR products to base composition Base composition signature from multiple PCR products is then used to identify the influenza virus species and subtype | Automated nucleic acid isolation Manual transfer of sample eluate to PCR Plate Automated PCR amplification Optical detection of stimulated fluorescence The fluorescence reader monitors real-time fluorescence during every PCR amplification cycle | Automated nucleic acid isolation Manual transfer of sample eluate to PCR Plate Automated PCR amplification Optical detection of stimulated fluorescence The fluorescence reader monitors real-time fluorescence during every PCR amplification cycle | Nucleic Acid isolation instrument Amplification and detection instrument | Automated nucleic acid isolation instrument (MagNA Pure LC System using the Total Nucleic Acid Isolation (TNAI) Kit or NucliSENS easyMAG System using the Automated Magnetic Extraction Reagents) | Automated PCR amplification and detection by fluorescence analysis (Cepheid SmartCycler II) |
| Instrumentation
Principle
System
Components | The PLEX-ID System integrates sample preparation (PLEX-ID SP, PLEX-ID FH) with PCR amplification (PLEX-ID TC) followed by mass spectrometry analysis to generate assay results (PLEX-ID Analyzer). | | | Nucleic Acid isolation instrument Amplification and detection instrument | Automated nucleic acid isolation instrument (MagNA Pure LC System using the Total Nucleic Acid Isolation (TNAI) Kit or NucliSENS easyMAG System using the Automated Magnetic Extraction Reagents) | Automated PCR amplification and detection by fluorescence analysis (Cepheid SmartCycler II) |
| Sample
Preparation
Instrument
Components | Liquid handling and robotic manipulation platform (PLEX-ID SP, PLEX-ID FH) using the PLEX-ID Viral RNA Isolation Kit | | | | | |
| Amplification
and
Detection
Instrument | Automated PCR amplification (PLEX-ID TC) is followed by mass spectrometry analysis and influenza virus identification (PLEX-ID | | | | | |

510(k) Summary

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9

Feature	Current Application	Predicate Devices
Amplification
Controls	PLEX-ID Flu Each PCR reaction well contains an Amplification Control that consists of a synthetic RNA molecule specific to the primer pairs used, but distinguishable from known target sequences. The Amplification Control serves as the internal PCR control and provides scaling information for the level of influenza RNA present in the sample. It also detects PCR inhibition, reagent failure, and process errors.	Prodesse ProFLU+ Internal Control to detect PCR inhibition in individual samples and Reagent failure or process error Prodesse ProFAST+ Internal Control to detect PCR inhibition in individual samples and Reagent failure or process error
Amplification
Enzyme
Type(s)	DNA Polymerase Reverse Transcriptase	Taq DNA Polymerase Reverse Transcriptase Taq DNA Polymerase Reverse Transcriptase
Detection
Procedure	Mass Spectrometry analysis converts mass of PCR products to base composition Base composition signature from multiple PCR products is then used to identify the influenza virus species and subtype	Optical detection of stimulated fluorescence. The fluorescence reader monitors real-time fluorescence during every PCR amplification cycle. Optical detection of stimulated fluorescence. The fluorescence reader monitors real-time fluorescence during every PCR amplification cycle.
Feature	Current Application
PLEX-ID Flu	Predicate Devices
Prodesse ProFLU+	Predicate Devices
Prodesse ProFAST+
Limit of
Detection
(LOD)	Influenza A H1N1 (2009) (Strain A/SwineNY/02/2009 H1N1) – $1.3 × 10^{-1}$ TCID50/mL Influenza A H1N1 (seasonal) (Strain A/New Caledonia/20/99 H1N1) – 4.6 TCID50/mL Influenza A H3N2 (seasonal) (Strain A/Wisconsin/67/05 H3N2) – $3.3 × 10^{2}$ TCID50/mL Seasonal Influenza B (Strain B/Panama/45/90) – 15 TCID50/mL	Influenza A/Port Chalmers/1/73 (H3N2) – $10^{1}$ TCID50/mL Influenza A/CA/7/04 (H3N2) – $10^{0}$ TCID50/mL Influenza A/New Caledonia/12/99 (H1N1) – $10^{2}$ TCID50/mL Influenza A/WS/33 (H1N1) – $10^{0}$ TCID50/mL Influenza B/Lee/40 – $10^{1}$ TCID50/mL Influenza B/Wisconsin/2/06 – $10^{0}$ TCID50/mL	H1N1 A/Virginia/1/06 – $5 × 10^{-1}$ TCID50/mL H1N1 A/Hong Kong/2652/06 – $5 × 10^{-2}$ TCID50/mL H3N2 A/Anhui/1239/05 – $1 × 10^{1}$ TCID50/mL H3N2 A/California/07/04 – $5 × 10^{1}$ TCID50/mL 2009 H1N1 Clinical Isolate #1 – $1 × 10^{2}$ TCID50/mL 2009 H1N1 Clinical Isolate #5 – $1 × 10^{2}$ TCID50/mL
Assay
Controls	Negative Control Positive Control	Negative Control Positive Control Extraction Control	Negative Control Positive Control Extraction Control
Results
Reporting	The PLEX-ID Flu assay reports results for both influenza A and influenza B in separate sections of the report. The influenza A report can show the following under Detected Microbe: 2009 (Pandemic) H1N1 Influenza A Seasonal H1N1 Influenza A Seasonal H3N2 Influenza A Other influenza A Not Detected The influenza B report can show the following under Detected Microbe: Seasonal Influenza B Not detected	Influenza A result of either "POS" for positive or "NEG" for negative for influenza A Influenza B result of either "POS" for positive or "NEG" for negative for influenza B "Unresolved" – PCR inhibition or reagent failure.	H1 result of either "POS" for positive or "NEG" for negative for Seasonal Influenza A/H1 H3 result of either "POS" for positive or "NEG" for negative for Seasonal Influenza A/H3 2009 H1N1 result of either "POS" for positive or "NEG" for negative for 2009 H1N1 Influenza RNA "Unresolved" – PCR inhibition or reagent failure.

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| Feature | Current Application
PLEX-ID Flu | Prodesse ProFLU+ | Predicate Devices
Prodesse ProFAST+ |
|---------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Drug /
Compound
Interference | Samples containing FluMist® may cause false positive results in the assay. FluMist is an intranasal vaccine that contains live attenuated influenza virus that is detected by the PLEX-ID Flu assay. No interference was detected from other common cold medicines or mucin | An interference study evaluating potentially interfering common cold medications was not performed. | The ProFAST+ assay was not affected by the presence of a panel of endogenous and exogenous potential RT-PCR inhibitors with the exception of mucin. Results indicate that mucin at a concentration of 5% and 1% w/v added to NP swab matrix, resulting in a highly viscous sample, had an inhibitory effect on detection of influenza A subtypes and the Internal RNA Control (IC) near the LoD using the ProFAST+ Assay. |
| Reagents and
Controls
Storage
Conditions | Frozen (-10°C or colder) | - 70°C or colder | - 70°C or colder |

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5.12 Performance Characteristics

5.12.1 Expected Values

The clinical performance of the PLEX-ID Flu assay on the PLEX-ID System was established using nasopharyngeal (NP) swab specimens prospectively collected from two U.S. clinical sites and three specimen suppliers from September 2009 through June 2010. A total of 1287 prospective NP swab specimens were collected for the PLEX-ID Flu clinical study. Of the 1287, five specimens were excluded: duplicate specimens were collected from two subjects (the second specimen from each subject was excluded from the analysis), one specimen from a subject who did not meet the inclusion criteria, and two specimens had an invalid PLEX-ID Flu result, for a total of 1282 included specimens. The prevalence of influenza A 2009 H1N1 decreased significantly during the collection period, consequently, there were only 37 positive influenza A 2009 H1N1, 4 positive influenza A HINI (seasonal), 50 positive influenza A H3N2 (seasonal), and 24 positive influenza B specimens among the 1282 specimens. Prevalence rates and demographics are presented in Table 2 and Table 3, respectively, for four of the five sites that provided prospectively collected specimens. No demographic information was available from supplier Site 3 (N=199) and one subject from clinical Site 1,

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Table 2

Influenza Prevalence Rate - Prospectively Collected Specimens

| | Number of Positives by the PLEX-ID Flu Assay
(Observed Prevalence Rate) | | | | |
|----------------|----------------------------------------------------------------------------|-----------|------------------|------------------|-------------|
| Age Group | N | 2009 H1N1 | Seasonal
H1N1 | Seasonal
H3N2 | Influenza B |
| 65 years | 35 | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Unknown* | 200 | 14 (7.0%) | 4 (2.0%) | 50 (25.0%) | 23 (11.5%) |
| Total | 1282 | 37 (2.9%) | 4 (0.3%) | 50 (3.9%) | 24 (1.9%) |

Demographic information was unavailable.

Table 3

Subject Demographics - Prospectively Collected Specimens

Gender/Age	Number of Subjects (%)
Female	603 (47.0%)
Male	479 (37.4%)
Unknown*	200 (15.6%)
Total	1282 (100.0%)

Demographic information was unavailable.

5.12.2 Clinical Performance

5.12.2.1 Prospective Clinical Study

Clinical performance of the PLEX-ID Flu assay was assessed by testing nasopharyngeal (NP) swab specimens from subjects presenting with symptoms of influenza-like illness.

Prospectively collected clinical specimens were tested at three sites. All specimens were

tested with an assay FDA cleared for the detection and discrimination of influenza A

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purified from NP swab specimens obtained from symptomatic patients (Comparator 1). Specimens with a positive influenza A test result went on for further testing with Comparator 2, an assay FDA cleared for the detection and discrimination of influenza A virus subtypes [influenza A HINI (2009), influenza A H1NI (seasonal), influenza A H3N2 (seasonal)] from nucleic acids isolated and purified from NP swab specimens. Aliquots from the same specimens were tested with the PLEX-ID Flu assay. For each subtype of influenza A [H]N] (2009), H1N1 (seasonal), H3N2 (seasonal)], the point estimate for positive percent agreement (PPA) and negative percent agreement (NPA) was calculated. PCR followed by bi-directional sequencing was used to test discrepant samples between Comparator 1 and Comparator 2, Comparator 1 vs. PLEX-ID Flu. and Comparator 2 vs. PLEX-ID Flu. The results from bi-directional sequence testing were not used to calculate the positive percent agreement and negative percent agreement of the PLEX-ID Flu assay.

Of the 1282 specimens included in the study, 6 were unresolved by Comparator 1 and were excluded, resulting in 1276 specimens included in the final analysis.

A total of 90 unique specimens were influenza A positive by Comparator 1 and 1186 were negative. All 90 specimens were tested by Comparator 2 to determine influenza A subtypes [influenza A HINI (2009), influenza A H1N1 (seasonal), influenza A H3N2 (seasonal)]. From these 90 unique specimens, 6 were negative for all three subtypes by Comparator 2. The remaining 84 specimens generated a total of 88 positive results. Four specimens generated two different subtype results each by Comparator 2. For one of these four specimens, Comparator 2 assay reported both HIN1 and H3N2 while the PLEX-ID Flu assay reported an HIN1 (seasonal) result. For the remaining 3 specimens, Comparator 2 reported both H3N2 and H1N1, whereas the PLEX-ID Flu assay reported H3N2 (seasonal). These 88 positive results comprised 32 influenza A H1N1 (2009), 7 influenza A HINI (seasonal) positive, and 49 influenza A H3N2 (seasonal) positive results.

From the 1287 prospective NP swab specimens collected for this study and tested, 98.7% (1285/1302) of PLEX-ID assays results generated were valid.

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The comparison of the PLEX-ID Flu assay and Comparator 2 results for influenza A HINI (2009) are shown in Table 4, influenza A HINI (seasonal) in Table 5, and influenza A H3N2 (seasonal) in Table 6.

Table 4

PLEX-ID Flu

Influenza A H1N1 (2009) Specimen Testing

| | Comparator 2
Positive | Comparatora
Negative | Total |
|----------------------------------|--------------------------------------------------------------------|----------------------------------------------------------------------|-------|
| PLEX-ID Flu
Positive | 32 | 5b | 37 |
| PLEX-ID Flu
Negative | 0 | 1239 | 1239 |
| Total | 32 | 1244 | 1276 |
| Percent
Agreement
(95% CI) | Positive Percent
Agreement
100.0% (32/32)
(89.3%, 100.0%) | Negative Percent
Agreement
99.6% (1239/1244)
(99.1%, 99.8%) | |

4 Negative for influenza A by Comparator 1 (and therefore untested by Comparator 2) or positive for influenza A by Comparator 1 and negative by Comparator 2 reflex testing for influenza A HINI (2009).

brive samples were negative for influenza A 2009 H1N1 by Comparator 2; three samples were positive by bi-directional sequence analysis for 2009 HINI, one had insufficient sample volume for bidirectional sequence analysis, and 2009 HIN1 nucleic acid was not detected by bi-directional sequence analysis in one sample.

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Table 5

PLEX-ID Flu

Influenza A H1N1 (Seasonal) Specimen Testing

| | Comparator 2
Positive | Comparatora
Negative | Total |
|----------------------------------|----------------------------------------------------------------|------------------------------------------------------------------------|-------|
| PLEX-ID Flu
Positive | 4 | 0 | 4 |
| PLEX-ID Flu
Negative | 3b | 1269 | 1272 |
| Total | 7 | 1269 | 1276 |
| Percent
Agreement
(95% CI) | Positive Percent
Agreement
57.1% (4/7)
(25.0%, 84.2%) | Negative Percent
Agreement
100.0% (1269/1269)
(99.7%, 100.0%) | |

"Negative for influenza A by Comparator 1 (and therefore untested by Comparator 2) or positive for influenza A by Comparator 1 and negative by Comparator 2 reflex testing for influenza A H1N1 (Seasonal).

6/H1 nucleic acids were not detected by bi-directional sequence analysis in these three samples.

Table 6

PLEX-ID Flu

Influenza A H3N2 (Seasonal) Specimen Testing

| | Comparator 2
Positive | Comparatora
Negative | Total |
|----------------------------------|------------------------------------------------------------------|-----------------------------------------------------------------------|-------|
| PLEX-ID Flu
Positive | 48 | 2b | 50 |
| PLEX-ID Flu
Negative | 1c | 1225 | 1226 |
| Total | 49 | 1227 | 1276 |
| Percent
Agreement
(95% CI) | Positive Percent
Agreement
98.0% (48/49)
(89.3%, 99.6%) | Negative Percent
Agreement
99.8% (1225/1227)
(99.4%, 100.0%) | |

"Negative for influenza A by Comparator 1 (and therefore untested by Comparator 2) or positive for influenza A by Comparator 1 and negative by Comparator 2 reflex testing for influenza A H3N2 (Seasonal).

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o Two samples were negative for influenza A by Comparator 1 and were not reflexed to Comparator 2 for subtype determination, but the samples were positive by bi-directional sequence analysis for A/H3. 6 A/H3 nucleic acid was not detected by bi-directional sequence analysis in this sample.

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A total of 22 positive specimens were obtained for influenza B. The positive percent agreement and negative percent agreement were calculated. The results of the PLEX-ID Flu compared to Comparator 1 for the detection of influenza B are shown in Table 7. Bidirectional sequence analysis was not performed for discordant influenza B specimens.

Table 7

PLEX-ID Flu

Influenza B Specimen Testing

| | Comparator 1
Positive | Comparator 1
Negative | Total |
|----------------------------------|--------------------------------------------------------------------|-----------------------------------------------------------------------|-------|
| PLEX-ID Flu
Positive | 22 | 2 | 24 |
| PLEX-ID Flu
Negative | 0 | 1252 | 1252 |
| Total | 22 | 1254 | 1276 |
| Percent
Agreement
(95% CI) | Positive Percent
Agreement
100.0% (22/22)
(85.1%, 100.0%) | Negative Percent
Agreement
99.8% (1252/1254)
(99.4%, 100.0%) | |

5.12.2.2 Retrospective Specimen Testing

Due to the decreased prevalence of influenza A 2009 H1N1 and the absence of influenza A seasonal H1N1 and H3N2, the prospectively collected specimen population was supplemented with pre-selected banked specimens that were collected in February 2008, and from January 2009 through March 2009, and left over archived specimens collected from April 2009 through December 2009.

A total of 1378 retrospective specimens were tested. Of these specimens, 1341 were included in the analysis (the remaining 37 were excluded either due to unavailable results for the PLEX-ID Flu assay or Comparator 1 assay, duplicate subjects, or failure to meet subject inclusion criteria).

Of the 1341 retrospective specimens, 634 were influenza A positive and 707 were negative by Comparator 1. All 634 positive specimens were tested to determine influenza A subtype (influenza A 2009 H1N1, influenza A (seasonal) HINI, influenza A

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(seasonal) H3N2). Two specimens were unresolved by Comparator 2 and, therefore, excluded, resulting in 1339 total specimens in the analysis. Fifty-four of the 634 Comparator 1 influenza A positive specimens were negative for all three subtypes by Comparator 2 and were included as Comparator negative specimens. Consequently, 578 positive results were included in the analysis: 548 influenza A HINI (2009), 28 influenza A HINI (seasonal), and 2 influenza A H3N2 (seasonal).

From the 1378 retrospective NP swab specimens tested in this study, 93.4% (1368/1464) of PLEX-ID assays results generated were valid.

The comparison of the PLEX-ID Flu and Comparator 2 results for influenza A H1N1 (2009) are shown in Table 8, influenza A H1N1 (seasonal) in Table 9, and influenza A H3N2 (seasonal) in Table 10.

The following analysis was performed on the leftover archived and pre-selected banked specimens.

Table 8

PLEX-ID Flu

| | Comparator 2
Positive | Comparatora
Negative | Total |
|----------------------------------|--------------------------------------------------------------------|--------------------------------------------------------------------|-------|
| PLEX-ID Flu
Positive | 538 | 45b | 583 |
| PLEX-ID Flu
Negative | 10c | 746 | 756 |
| Total | 548 | 791 | 1339 |
| Percent
Agreement
(95% CI) | Positive Percent
Agreement
98.2% (538/548)
(96.7%, 99.0%) | Negative Percent
Agreement
94.3% (746/791)
(92.5%, 95.7%) | |

Influenza A H1N1 (2009) Specimen Testing

"Negative for influenza A by Comparator 1 (and therefore untested by Comparator 2) or positive for influenza A by Comparator 1 and negative by Comparator 2 reflex testing for influenza A HINI (2009). 841 samples were positive by bi-directional sequence analysis for 2009 H1N1, 1 was unresolved, 2 had insufficient sample volume for bi-directional sequence analysis, and HINI(2009) nucleic acid was not detected in one sample.

CA/HINI (2009) was detected in 8 samples by bi-directional sequence analysis.

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Table 9

PLEX-ID Flu

Influenza A H1N1 (Seasonal) Specimen Testing

| | Comparator 2
Positive | Comparatora
Negative | Total |
|----------------------------------|------------------------------------------------------------------|------------------------------------------------------------------------|-------|
| PLEX-ID Flu
Positive | 27 | 0 | 27 |
| PLEX-ID Flu
Negative | 1b | 1311 | 1312 |
| Total | 28 | 1311 | 1339 |
| Percent
Agreement
(95% CI) | Positive Percent
Agreement
96.4% (27/28)
(82.3%, 99.4%) | Negative Percent
Agreement
100.0% (1311/1311)
(99.7%, 100.0%) | |

"Negative for influenza A by Comparator 1 (and therefore untested by Comparator 2) or positive for influenza A by Comparator 1 and negative by Comparator 2 reflex testing for influenza A HINI (Seasonal).

b A/H I nucleic acid was not detected by bi-directional sequence analysis in this sample.

Table 10

PLEX-ID Flu

Influenza A H3N2 (Seasonal) Specimen Testing

| | Comparator 2
Positive | Comparatorᵃ
Negative | Total |
|----------------------------------|------------------------------------------------------------------|------------------------------------------------------------------------|-------|
| PLEX-ID Flu
Positive | 2 | 0 | 2 |
| PLEX-ID Flu
Negative | 0 | 1337 | 1337 |
| Total | 2 | 1337 | 1339 |
| Percent
Agreement
(95% CI) | Positive Percent
Agreement
100.0% (2/2)
(34.2%, 100.0%) | Negative Percent
Agreement
100.0% (1337/1337)
(99.7%, 100.0%) | |

"Negative for influenza A by Comparator 1 (and therefore untested by Comparator 2) or positive for influenza A by Comparator 1 and negative by Comparator 2 reflex testing for influenza A H3N2 (Seasonal).

A total of 28 positive specimens were obtained for influenza B. The positive percent agreement and negative percent agreement were calculated. The comparison results of the PLEX-ID Flu and Comparator 1 to detect influenza B are shown in Table 11. Bidirectional sequence analysis was not performed for discordant influenza B specimens.

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Table 11

PLEX-ID Flu

Influenza B Specimen Testing

| | Comparator 1
Positive | Comparator 1
Negative | Total |
|----------------------------------|------------------------------------------------------------------|-----------------------------------------------------------------------|-------|
| PLEX-ID Flu
Positive | 26 | 1 | 27 |
| PLEX-ID Flu
Negative | 2 | 1312 | 1314 |
| Total | 28 | 1313 | 1341 |
| Percent
Agreement
(95% CI) | Positive Percent
Agreement
92.9% (26/28)
(77.4%, 98.0%) | Negative Percent
Agreement
99.9% (1312/1313)
(99.6%, 100.0%) | |

5.12.2.3 Other Clinical Supportive Data

Not applicable.

5.12.2.4 Clinical Cut-Off

Not applicable.

5.12.3 Summary of Nonclinical Studies

5.12.4 Limit of Detection

The limit of detection (LOD) for the PLEX-ID Flu assay was determined by testing quantitated influenza strains diluted in negative nasopharyngeal swab matrix. Twenty replicates of the following were tested: influenza A HINI (2009), influenza A H1N1 (seasonal), influenza A H3N2 (seasonal), and influenza B. The LOD was defined as the lowest influenza concentration at which ≥ 95% of replicates tested positive. The results are presented in Table 12.

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Influenza	Limit of Detection (TCID50/mL)
influenza A H1N1 (2009)	$1.3 \times 10^{1}$
influenza A H1N1 (seasonal)	$4.6 \times 10^{0}$
influenza A H3N2 (seasonal)	$3.3 \times 10^{2}$
influenza B	$1.5 \times 10^{1}$

Table 12 PLEX-ID Flu Limit of Detection (LOD)

5.12.4.1 Reproducibility

The reproducibility of the PLEX-ID Flu assay was evaluated at 3 clinical sites. Reproducibility was assessed using a nine member panel of contrived samples that included a negative member, low positive panel members targeted near the assay LOD and moderate positive panel members targeted at approximately 2 to 3 times the LOD for influenza B and the 3 influenza A subtypes detected by the assay. Samples were tested in replicates of 4 with one replicate each of the positive and negative control per batch. Two (2) batches were run per day and each was run by a different operator with 2 operators per site. The study was designed to allow for a total of 120 results for each panel member over 5 days of testing. The results are presented in Table 13.

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Table 13
PLEX-ID Flu
Reproducibility Study

:

| Panel Member Description | Correct Results/Number Tested
(% Agreement) | | | Total of All Sites
(95% CI) |
|-----------------------------------------------|------------------------------------------------|--------------------|--------------------|--------------------------------------|
| | Site 1 | Site 2 | Site 3 | |
| Negative | 40/40
(100.0%) | 40/40
(100.0%) | 40/40
(100.0%) | 120/120 (100.0%)
(96.9%, 100.0%) |
| influenza A H1N1 (2009) Low Positive | 40/40
(100.0%) | 39/39a
(100.0%) | 38/40
(95.0%) | 117/119a (98.3%)
(94.1%, 99.5%) |
| influenza A H1N1 (2009) Moderate Positive | 40/40
(100.0%) | 40/40
(100.0%) | 40/40
(100.0%) | 120/120 (100.0%)
(96.9%, 100.0%) |
| influenza A H1N1 (seasonal) Low Positive | 39/40
(97.5%) | 40/40
(100.0%) | 39/40
(97.5%) | 118/120 (98.3%)
(94.1%, 99.5%) |
| influenza A H1N1 (seasonal) Moderate Positive | 40/40
(100.0%) | 40/40
(100.0%) | 40/40
(100.0%) | 120/120 (100.0%)
(96.9%, 100.0%) |
| influenza A H3N2 (seasonal) Low Positive | 40/40
(100.0%) | 40/40
(100.0%) | 39/39a
(100.0%) | 119/119a (100.0%)
(96.9%, 100.0%) |
| influenza A H3N2 (seasonal) Moderate Positive | 39/40
(97.5%) | 40/40
(100.0%) | 40/40
(100.0%) | 119/120 (99.2%)
(95.4%, 99.9%) |
| influenza B Low Positive | 40/40
(100.0%) | 39/39a
(100.0%) | 39/40
(97.5%) | 118/119a (99.2%)
(95.4%, 99.9%) |
| influenza B Moderate Positive | 40/40
(100.0%) | 40/40
(100.0%) | 39/40
(97.5%) | 119/120 (99.2%)
(95.4%, 99.9%) |

ªMissing replicate due to instrument error.

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5.12.4.2 ·Within Laboratory Precision

Within laboratory precision was determined by testing all nine members of the reproducibility panel in duplicate in two runs per day for a total of twelve days. Each run contained the assay positive and negative controls for a total of 20 samples per run. Multiple PLEX-ID Flu assay lots were used in the study. The results are presented in Table 14.

| Table
1

1	0
-----------------	---

PLEX-ID Flu Within Laboratory Precision

| Panel Member Description | Correct Results/Number Tested
(% Agreement) | 95%
Confidence
Interval |
|--------------------------------------------------|------------------------------------------------|-------------------------------|
| Negative | 48/48 (100%) | (93%, 100%) |
| influenza A HINI (2009)
Low Positive | 48/48 (100%) | (93%, 100%) |
| influenza A H1N1 (2009)
Moderate Positive | 48/48 (100%) | (93%, 100%) |
| influenza A H1N1 (seasonal)
Low Positive | 48/48 (100%) | (93%, 100%) |
| influenza A HIN1 (seasonal)
Moderate Positive | 48/48 (100%) | (93%, 100%) |
| influenza A H3N2 (seasonal)
Low Positive | 48/48 (100%) | (93%, 100%) |
| influenza A H3N2 (seasonal)
Moderate Positive | 48/48 (100%) | (93%, 100%) |
| influenza B
Low Positive | 48/48 (100%) | (93%, 100%) |
| influenza B
Moderate Positive | 48/48 (100%) | (93%, 100%) |

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5.12.4.3 Cross-Reactivity

The effect of 34 common respiratory microbes on the PLEX-ID Flu assay was evaluated. Negative samples and samples containing influenza A HINI (2009), influenza A HINI (seasonal), influenza A H3N2 (seasonal), and influenza B were tested. No interference in the performance of the PLEX-ID Flu assay was observed in the presence of the potential cross-reactants shown in Table 15 for all positive and negative samples tested.

Table 15 PLEX-ID Flu Cross-Reactivity

| Microbe | Target Spike
Concentration |
|--------------------------------------|-------------------------------|
| Bordetella pertussis | 106 CFU/mL |
| Chlamydia pneumoniae | 106 CFU/mL |
| Corynebacterium sp. | 106 CFU/mL |
| Escherichia coli | 106 CFU/mL |
| Haemophilus influenzae | 106 CFU/mL |
| Lactobacillus sp. | 106 CFU/mL |
| Legionella pneumophilia | 106 CFU/mL |
| Moraxella cartarrhalis | 106 CFU/mL |
| Mycobacterium tuberculosis avirulent | 106 genomes/mL |
| Mycoplasma pneumoniae | 106 CFU/mL |
| Neisseria meningitides | 106 CFU/mL |
| Neisseria sp. | 105 CFU/mL |
| Pseudomonas aeruginosa | 106 CFU/mL |
| Staphylococcus aureus | 106 CFU/mL |
| Staphylococcus epidermidis | 106 CFU/mL |
| Streptococcus pneumoniae | 106 CFU/mL |
| Streptococcus pyogenes | 106 CFU/mL |

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| Microbe | Target Spike
Concentration |
|------------------------------------|-------------------------------|
| Streptococcus salivarius | $10^5$ CFU/mL |
| Adenovirus Type 1 | $10^5$ TCID50/mL |
| Adenovirus Type 7 | $10^5$ TCID50/mL |
| Human coronavirus OC 43 | $10^4$ TCID50/mL |
| Human coronavirus OC229E | $10^5$ TCID50/mL |
| Cytomegalovirus | $10^5$ TCID50/mL |
| Enterovirus | $10^5$ TCID50/mL |
| Epstein Barr virus | $10^5$ TCID50/mL |
| Measles | $10^5$ TCID50/mL |
| Human metapneumovirus | $10^5$ TCID50/mL |
| Mumps virus | $10^5$ TCID50/mL |
| Respiratory syncytial virus Type B | $10^5$ TCID50/mL |
| Rhinovirus Type 1A | $10^4$ TCID50/mL |
| Human parainfluenza Type 1 | $10^5$ TCID50/mL |
| Human parainfluenza Type 2 | $10^5$ TCID50/mL |
| Human parainfluenza Type 3 | $10^5$ TCID50/mL |
| Herpes simplex virus Type 1 | $10^5$ TCID50/mL |

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5.12.4.4 Potentially Interfering Substances

The effect of substances that may be present in nasopharyngeal swab samples for potential interference with the PLEX-ID Flu assay was evaluated. Negative samples and samples containing influenza A HINI (2009), influenza A HIN1 (seasonal), influenza A H3N2 (seasonal), and influenza B were tested at concentrations approximately 2× LOD. No interference in the performance of the PLEX-ID Flu assay was observed in the presence of the potentially interfering substances shown in Table 16 for all positive and negative samples tested.

FluMist®, an intranasal vaccine that contains live attenuated influenza virus, was detected by the PLEX-ID Flu assay. Samples containing FluMist may cause false positive results in the assay.

Mucin: bovine submaxillary gland, type I-S	Boiron Sulphur iodatum
Blood (human)	Cepacol Dual Relief Sore Throat Spray
Neo-Synephrine	CVS Pharmacy Sore Throat Spray
Equaline 12-hour Nasal Spray	Cool Mint Listerine Antiseptic
Equaline Premium Saline Nasal Spray	Halls Mentho-Lyptus
Beconase	Tamiflu
Decadron	Flumadine
Nasarel	SYMMETREL
Allernaze	Relenza
Rhinocort Aqua Nasal Spray	BACTROBAN NASAL
Nasonex	Tobi
Oxymetazonine HCl	Adult Robitussin Chest Congestion
Flonase	CVS Children's Allergy Liquid
Medication
Zicam	Delsym Cough Suppressant

Table 16 PLEX-ID Flu Potentially Interfering Substances

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Boiron Galphimia glauca	CVS Non-Drowsy Nasal Decongestant
Boiron Histaminum hydrochloricum

5.12.4.5 Carryover

Sample carryover on the PLEX-ID System was evaluated using high target concentrations (1 × 105 viral genomes per mL) of influenza A and influenza B alternately loaded with negative sample rack, representing a worst-case, checkerboard configuration. Following 5 independent isolations, no positive results were reported among the 120 negative samples tested, resulting in an observed carryover rate of 0% (0/120).

5.12.4.6 Inclusivity

Multiple viral strains representing temporal and geographical diversity for each influenza type and subtype were tested with the PLEX-ID Flu assay. The samples were targeted at concentrations at approximately 2× LOD. The results reported for each strain tested matched the expected result in 3 out of 3 replicates, as shown in Table 17.

Table 17 PLEX-ID Flu Inclusivity

Viral Strain	Concentration	Influenza A H1N1 (2009)	Influenza A H1N1 (seasonal)	Influenza A H3N2 (seasonal)	Influenza A Other	Influenza B
influenza A Swine H1N1 NY01 (2009 H1N1)	6.57 TCID50/mL	+	-	-	-	-
influenza A Swine H1N1 NY02 (2009 H1N1)	$1.06x10^1$ TCID50/mL	+	-	-	-	-
influenza A Swine H1N1 NY03 (2009 H1N1)	9.37 TCID50/mL	+	-	-	-	-
influenza A/Brisbane/59/07	$1.37\times10^1$ TCID50/mL	-	+	-	-	-
Viral Strain	Concentration	Influenza A H1N1
(2009)	Influenza A H1N1
(seasonal)	Influenza A H3N2
(seasonal)	Influenza A Other	Influenza B
(Seasonal H1N1)
influenza
A/NewCal/20/1999
(Seasonal H1N1)	$1.29×10^3$ TCID50/mL	-	+	-	-	-
influenza A/Taiwan/42/06
(Seasonal H1N1)	$4.45×10^3$ TCID50/mL	-	+	-	-	-
influenza A/Solomon
Islands/03/06
(Seasonal H1N1)	$1.40×10^1$ TCID50/mL	-	+	-	-	-
influenza A/PR/8/34
(Seasonal H1N1)	$4.02×10^4$ CEID50/mL	-	+	-	-	-
influenza A/WS/33
(Seasonal H1N1)	$4.14×10^2$ CEID50/mL	-	+	-	-	-
influenza A/New
Jersey/8/76 (Seasonal
H1N1)	$1.24×10^2$ CEID50/mL	-	+	-	-	-
influenza A/Weiss/43
(Seasonal H1N1)	$3.41×10^6$ CEID50/mL	-	+	-	-	-
influenza A/FM/1/47
(Seasonal H1N1)	$6.52×10^3$ CEID50/mL	-	+	-	-	-
influenza A/Mal/302/54
(Seasonal H1N1)	$7.41×10^2$ CEID50/mL	-	+	-	-	-
influenza A/Port
Chalmers/1/73 (Seasonal
H3N2)	$6.15×10^3$ CEID50/mL	-	-	+	-	-
influenza A/Hong
Kong/8/68 (Seasonal
H3N2)	$4.12×10^4$ CEID50/mL	-	-	+	-	-
influenza A/Victoria/3/75
(Seasonal H3N2)	$2.46×10^3$ CEID50/mL	-	-	+	-	-
Viral Strain	Concentration	Influenza A H1N1 (2009)	Influenza A H1N1 (seasonal)	Influenza A H3N2 (seasonal)	Influenza A Other	Influenza B
influenza A/Aichi/2/68
(Seasonal H3N2)	$4.72\times10^3$ CEID50/mL	-	-	+	-	-
influenza B/Lee/40	$3.28\times10^4$ CEID50/mL	-	-	-	-	+
influenza B/Mass/3/66	$9.41\times10^3$ CEID50/mL	-	-	-	-	+
influenza B/Taiwan/2/62	$1.65\times10^2$ CEID50/mL	-	-	-	-	+
influenza B/Hong Kong/5/72	$2.63\times10^4$ CEID50/mL	-	-	-	-	+
influenza B/GL/1739/54	$1.56\times10^3$ CEID50/mL	-	-	-	-	+
influenza B/Allen/45	$1.30\times10^2$ CEID50/mL	-	-	-	-	+
influenza B/Maryland/1/59	8.50 CEID50/mL	-	-	-	-	+
influenza B/Russia/69	$1.24\times10^3$ CEID50/mL	-	-	-	-	+
influenza B/Florida/02/06	$8.11\times10^1$ TCID50/mL	-	-	-	-	+
influenza B/Malaysia/2506/04	$2.07\times10^1$ TCID50/mL	-	-	-	-	+

PLEX-ID FIL December 2012

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510(k) Summary
Page 29 of 31

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ﺘﺮﺍ ﻓﻲ ﺍﻟﻤﺘﻮﺳﻂ ﺍﻟﺘﻲ ﺗﻌﺘﺒﺮ ﺍﻟﻤﺘﻮﺳﻂ ﺍﻟﺘﻲ ﺗﻌﺘﺒﺮ ﺍﻟﻤﺘﻮﺳﻂ ﺍﻟﻤﺘﻮﺳﻂ ﺍﻟﻤﺘﻮﺳﻂ ﺍﻟﻤﺘﻮﺳﻂ ﺍﻟﻤﺘﻮﺳﻂ ﺍﻟﻤﺘﻮﺳﻂ ﺍﻟﻤﺘﻮﺳﻂ ﺍﻟﻤﺘﻮﺳﻂ ﺍﻟﻤﺘﻮﺳﻂ ﺍﻟﻤﺘﻮﺳﻂ ﺍﻟﻤﺘﻮﺳﻂ ﺍﻟﻤﺘﻮﺳﻂ ﺍﻟﻤﺘﻮﺳﻂ ﺍﻟﻤﺘﻮﺳﻂ ﺍﻟﻤﺘﻮﺳﻂ ﺍﻟﻤﺘﻮﺳﻂ

·

30

5.13 References

CDC Influenza (Flu), What Everyone Should Know About Flu and the Flu l . Vaccine: www.cdc.gov/flu/keyfacts.htm [8/17/2009]
1. U.S. Department of Health & Human Services: www.flu.gov/about the flu/seasonal/index.html [9/17/2012]
Chan, Margaret. World now at the start of 2009 influenza pandemic, Statement to 3. the press by WHO Director-General Dr Margaret Chan 11 June 2009: http://www.who.int/mediacentre/news/statements/2009/h1n1 pandemic phase6 20 090611/en/index.html. September 2012.

PLEX-ID Flu 510(k) K121003 December 2012

510(k) Summary Page 31 of 31

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-002

Abbott Laboratories c/o Darren Clarke 1300 East Touhy Avenue Des Plaines, Illinois, 60018

December 21, 2012

Re: K121003

Trade/Device Name: Abbott Plex-ID Flu Assay Regulation Number: 21 CFR 866.3980 Regulation Name: Respiratory viral panel multiplex nucleic acid assay Regulatory Class: Class II Product Code: OCC, OEP, OQW, OTA Dated: December 15, 2012 Received: December 17, 2012

Dear Mr. Clarke:

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.

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 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.

32

If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostics and Radiological Health 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.

Uwe Scherf for

Sally A. 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

33

Indications of Use Statement

510(k) Number: K121003

4.0

Device Name: PLEX-ID Flu

Indications for Use for the PLEX-ID Flu:

The PLEX-ID Flu assay is a qualitative nucleic acid in vitro diagnostic test intended for the detection and differentiation of influenza A H1N1 (2009), influenza A H1N1 (seasonal), influenza A H3N2 (seasonal) and influenza B viral nucleic acids in nasopharyngeal swab specimens from patients symptomatic for respiratory tract infection. The PLEX-ID Flu assay is intended for use on the PLEX-ID System (version 1.2) as an aid in the diagnosis of influenza infection in conjunction with clinical and epidemiological information. This assay is not intended to detect 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.

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 departments 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 (Per 21 CFR 801.109) AND/OR

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

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

Concurrence of CDRH, Office of In Vitro Diagnostics and Radiological Health (OIR)

Tausael Feldberg
Division Sign-Off

Office of In Vitro Dlagnostic Device Evaluation and Safety

510(k) K121003