LIAT (TM) INFLUENZA A / B ASSAY, LIAT (TM) ANALYZER

K111387 · Iquum, Inc. · OCC · Aug 4, 2011 · Microbiology

Device Facts

• Record ID: K111387
• Device Name: LIAT (TM) INFLUENZA A / B ASSAY, LIAT (TM) ANALYZER
• Applicant: Iquum, Inc.
• Product Code: OCC · Microbiology
• Decision Date: Aug 4, 2011
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3980
• Device Class: Class 2
• Attributes: Pediatric

Intended Use

The IQuum Liat™ Influenza A/B Assay performed on the Liat™ Analyzer is an automated multiplex real-time RT-PCR assay for the rapid in vitro qualitative detection and discrimination of influenza A virus and influenza B virus RNA in nasopharyngeal swab specimens from patients with signs and symptoms of respiratory infection in conjunction with clinical and epidemiological risk factors. The test is intended for use as an aid in the differential diagnosis of influenza A and influenza B in humans and is not intended to detect influenza C. Negative results do not preclude influenza virus infection and should not be used as the sole basis for 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. Performance characteristics for influenza A were established when influenza A/H1 and A/H3 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.

Device Story

The Liat Influenza A/B Assay is a rapid, automated, in vitro diagnostic test performed on the Liat Analyzer. It uses nasopharyngeal swab specimens in universal transport media. The system utilizes 'lab-in-a-tube' technology: a disposable tube containing prepacked reagents in segments separated by peelable seals. The analyzer uses multiple actuators to compress the tube, selectively releasing reagents, moving samples, and controlling temperature/time for nucleic acid extraction, target enrichment, and real-time RT-PCR. It targets the matrix gene of Influenza A and the non-structural protein (NS) gene of Influenza B, with an Internal Process Control (IPC). The device is used in clinical settings (CLIA moderate/high complexity labs) by trained personnel. The analyzer provides automated result interpretation in ~20 minutes, displayed on a touchscreen and printable via USB. This rapid turnaround aids clinicians in timely differential diagnosis and patient management decisions, potentially reducing unnecessary testing or treatment.

Clinical Evidence

Clinical study included 615 specimens (435 prospective, 180 retrospective). Prospective samples compared against viral culture/IFA; retrospective samples compared against PCR/sequencing. For Influenza A (prospective), sensitivity was 100% (89.8-100.0% CI) and specificity 96.8% (94.5-98.1% CI). For Influenza B (prospective), sensitivity was 100% (88.6-100.0% CI) and specificity 94.1% (91.3-96.0% CI). Retrospective samples showed 100% positive agreement for both A and B. Reproducibility study across 3 sites, 2 operators, and 5 days showed total agreement ≥99.9%.

Technological Characteristics

Multiplex real-time RT-PCR assay. Targets: Influenza A matrix gene, Influenza B non-structural protein gene, and MS2 bacteriophage internal process control. Sample prep: chaotropic lysis and silica magnetic bead purification. Detection: TaqMan-probe based hydrolysis with reporter dyes (e.g., FAM) and quenchers (e.g., BHQ). Form factor: disposable Liat Tube (single-use) and Liat Analyzer (point-of-care instrument). Connectivity: standalone system with integrated PC and touchscreen. Software: embedded microprocessor controls fluidics and thermal cycling.

Indications for Use

Indicated for qualitative detection and discrimination of influenza A and B viral RNA in nasopharyngeal swab specimens from patients with signs/symptoms of respiratory infection. Intended as an aid in differential diagnosis. Not for detection of influenza C. Contraindicated for use as sole basis for treatment decisions; does not rule out bacterial or other viral co-infections.

Regulatory Classification

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.

Special Controls

*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.

Predicate Devices

• Cepheid Xpert® Flu Assay (K103766)

Submission Summary (Full Text)

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\$IQ^{uum}\$

IQuum, Inc. 700 Nickerson Road, Marlborough, MA 01752

Tel [phone] Fax [phone] www.lQuum.com

### 510(K) SUMMARY

AUG - 4 2011

| Applicant | IQuum, Inc.<br>700 Nickerson Road<br>Marlborough, MA 01752<br>Tel: [phone]<br>Fax: [phone] |
|---------------------|------------------------------------------------------------------------------------------------------------------------------------|
| Contact | Lingjun Chen<br>Title: Vice President, Operations & Business Development<br>Tel: [phone] ext. 116<br>Email: [e-mail] |
| Summary Date | May 16, 2011 |
| Trade Name | Liat™ Influenza A/B Assay, Liat™ Analyzer |
| Common Name | Influenza A, B Panel |
| Regulation Number | 21 CFR 866.3980 |
| Classification Name | Respiratory Viral Panel Multiplex Nucleic Acid Assay |
| Predicate Device: | Cepheid Xpert® Flu Assay (K103766) |

#### Intended Use

The IQuum Liat™ Influenza A/B Assay performed on the Liat™ Analyzer is an automated multiplex real-time RT-PCR assay for the rapid in vitro qualitative detection and discrimination of influenza A virus and influenza B virus RNA in nasopharyngeal swab specimens from patients with signs and symptoms of respiratory infection in conjunction with clinical and epidemiological risk factors. The test is intended for use as an aid in the differential diagnosis of influenza A and influenza B in humans and is not intended to detect influenza C.

Negative results do not preclude influenza virus infection and should not be used as the sole basis for 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.

Performance characteristics for influenza A were established when influenza A/H1 and A/H3 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.

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### Device Description

The Liat™ Influenza A/B Assay is a rapid, automated in vitro diagnostic test for the detection and differentiation of Influenza type A and type B viral RNA in nasopharyngeal swab (NPS) specimens in universal transport media (UTM) from patients signs and symptoms of respiratory infection. The assay targets a well-conserved region of the matrix gene of Influenza A viral RNA (Inf A target) and non-structural protein (NS) gene of Influenza B (Inf B target). An Internal Process Control (IPC) is also included. The IPC is present to control for adequate processing of the target viruses and to monitor the presence of inhibitors in the RT-PCR reactions.

The Liat Influenza A/B Assay is performed on the lab-in-a-tube technology platform. The system consists of a disposable Liat Influenza A/B Assay Tube and the Liat™ Analyzer. The Liat™ Tube uses a flexible tube as a sample vessel. It contains all required unit dose reagents prepacked in tube segments, separated by peelable seals, in the order of reagent use. Manipulating a Liat Tube, the Liat Analyzer performs all assay steps from raw sample and report assay result automatically, During the testing process, multiple sample processing actuators of the analyzer compress the Liat Tube to selectively release reagents from tube segments, move the sample from one segment to another, and control reaction volume, temperature and time to conduct sample preparation, nucleic acid extraction, target enrichment, inhibitor removal, nucleic acid elution and real-time RT-PCR. An embedded microprocessor controls and coordinates the actions of these sample processors to perform all required assay processes within the closed Liat Tube. Turnaround time from sample input to result is ~20 minutes.

### Test Operation

A nasopharyngeal swab can be collected following the user institution's standard procedures. For nasopharyngeal swab samples suspended in UTM, the user transfers 100 µl of the UTM sample into Liat Influenza A/B Assay tube. The user then scans the tube barcode to identify the test and scans sample barcode to code the sample ID using the Liat Tube is then inserted into the Liat Analyzer. The analyzer performs all test steps and outputs interpreted results in 20 minutes. A report of the interpreted results can be viewed in the View Results window, and printed directly through a USB connected printer.

No reagent preparation or addition steps are required, other than adding the sample to the Liat tube. Because all the reagents are contained within the Liat assay tube and no sample or reagent needs to be removed from the tube, cross-contamination between samples is minimized.

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## Predicate Device Comparison

Predicate Device: Cepheid Xpert® Flu Assay (K103766)

| | Device: | Predicate: |
|-----------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Item Name | Liat Influenza A/B | Cepheid Xpert Flu |
| Intended Use | The IQuum Liat™ Influenza A/B Assay<br>performed on the Liat™ Analyzer is an<br>automated multiplex real-time RT-PCR<br>assay for the rapid <i>in vitro</i> qualitative<br>detection and discrimination of<br>influenza A virus and influenza B virus<br>RNA in nasopharyngeal swab<br>specimens from patients with signs and<br>symptoms of respiratory infection in<br>conjunction with clinical and<br>epidemiological risk factors. The test is<br>intended for use as an aid in the<br>differential diagnosis of influenza A and<br>influenza B in humans and is not<br>intended to detect influenza C.<br><br>Negative results do not preclude<br>influenza virus infection and should not<br>be used as the sole basis for treatment or<br>other patient management decisions.<br>Conversely, positive results do not rule-<br>out bacterial infection or co-infection<br>with other viruses. The agent detected<br>may not be the definite cause of disease.<br><br>Performance characteristics for<br>influenza A were established when<br>influenza A/H1 and A/H3 were the<br>predominant influenza A viruses in<br>circulation. When other influenza A<br>viruses are emerging, performance<br>characteristics may vary.<br><br>If infection with a novel influenza A<br>virus is suspected based on current<br>clinical and epidemiological screening<br>criteria recommended by public health<br>authorities, specimens should be<br>collected with appropriate infection<br>control precautions for novel virulent | The Cepheid® Xpert Flu Assay is an<br>automated, multiplex real-time RT-<br>PCR assay intended for the <i>in vitro</i><br>qualitative detection and<br>differentiation of influenza A,<br>influenza B and 2009 H1N1 influenza<br>viral RNA. The Xpert Flu Assay uses<br>nasal aspirates/washes and<br>nasopharyngeal swab specimens<br>collected from patients with signs and<br>symptoms of respiratory infection in<br>conjunction with clinical and<br>epidemiological risk factors. The<br>Xpert Flu Assay is intended as an aid<br>in the diagnosis of influenza.<br><br>Negative results do not preclude<br>influenza virus infection and should<br>not be used as the sole basis for<br>treatment or other patient management<br>decisions.<br><br>Performance characteristics for<br>influenza A were established during<br>the 2009-2010 influenza season when<br>2009 H1N1 influenza was the<br>predominant influenza A virus in<br>circulation. When other influenza A<br>viruses are emerging, performance<br>characteristics may vary.<br><br>If infection with a novel influenza A<br>virus is suspected based on current<br>clinical and epidemiological screening<br>criteria recommended by public health<br>authorities, specimens should be<br>collected with appropriate infection<br>control precautions for novel virulent<br>influenza viruses and sent to state or<br>local health department for testing.<br>Viral culture should not be attempted in these cases unless a BSL 3+ facility |
| | | |
| | cases unless a BSL 3+ facility is | |
| | available to receive and culture | |
| | specimens. | |
| | <b>Device:</b> | <b>Predicate:</b> |
| Item Name | Liat Influenza A/B | Cepheid Xpert Flu |
| Regulation | 21 CFR 866.3980 | 21 CFR 866.3332 |
| Product Code | OCC, OOI | OQW, OCC, OOI |
| Assay Target | Influenza A<br>Influenza B | Influenza A<br>Influenza B<br>Influenza A subtype 2009 H1N1 |
| Sample Type | Nasopharyngeal Swab | Nasopharyngeal Swab<br>Nasal aspirates/washes |
| Internal Control | Yes | Yes |
| Influenza A Viral<br>Target | Matrix gene | Matrix gene |
| Influenza B Viral<br>Target | Non-structural protein (NSP) gene | Hemagglutinin gene |
| Assay Instrument | LiatTM Analyzer | GeneXpert instruments |
| Self-contained<br>System | Integrated PC, software, and touch-<br>screen display | External PC computer and software<br>for running tests and viewing the<br>results |
| All Assay<br>Reagents<br>Contained in<br>Disposable | No manual reagent addition required | Requires manual dispensing of<br>Binding Reagent into the chamber<br>with the small opening of the Xpert<br>Flu Assay Cartridge |
| Automated Assay | Yes, sample preparation, amplification,<br>detection and result interpretation | Yes, sample preparation,<br>amplification, detection and result<br>interpretation |
| Extraction Method | Sample preparation integrated in Liat Tube<br>and Liat Analyzer | Sample preparation integrated in<br>GeneXpert Cartridge and GeneXpert<br>Instrument |
| Assay Method | RT-PCR for detecting the presence /<br>absence of viral RNA in clinical<br>specimens | RT-PCR for detecting the presence /<br>absence of viral RNA in clinical<br>specimens |
| Detection<br>Technique | Multiplex assay using different reporter<br>dyes for each target | Multiplex assay using different<br>reporter dyes for each target |
| Result<br>Interpretation | Automated | Automated…