XTAG RESPIRATORY VIRAL PANEL, MODELS I019A0110, I019C011, I019D0112, I019E0113, S019-0116

K091667 · Luminex Molecular Diagnostics, Inc. · OCC · Jun 25, 2009 · Microbiology

Device Facts

• Record ID: K091667
• Device Name: XTAG RESPIRATORY VIRAL PANEL, MODELS I019A0110, I019C011, I019D0112, I019E0113, S019-0116
• Applicant: Luminex Molecular Diagnostics, Inc.
• Product Code: OCC · Microbiology
• Decision Date: Jun 25, 2009
• Decision: SESE
• Submission Type: Special
• Regulation: 21 CFR 866.3980
• Device Class: Class 2

Intended Use

The xTAG Respiratory Viral Panel (RVP) is a qualitative nucleic acid multiplex test intended for the simultaneous detection and identification of multiple respiratory virus nucleic acids in nasopharyngeal swabs from individuals suspected of respiratory tract infections. The following virus types and subtypes are identified using RVP: Influenza A, Influenza A subtype H1, Influenza A subtype H3, Influenza B, Respiratory Syncytial Virus subtype A, Respiratory Syncytial Virus subtype B, Parainfluenza 1, Parainfluenza 2, and Parainfluenza 3 virus, Human Metapneumovirus, Rhinovirus, and Adenovirus. The detection and identification of specific viral nucleic acids from individuals exhibiting signs and symptoms of respiratory infection aids in the diagnosis of respiratory viral infection if used in conjunction with other clinical and laboratory findings. It is recommended that specimens found to be negative for Influenza B, Respiratory Synctial Virus subtype A and B, Parainfluenza 2, Parainfluenza 3 and Adenovirus, after examination using RVP be confirmed by cell culture. Negative results do not preclude respiratory virus infection and should not be used as the sole basis for diagnosis, treatment or other management decisions. Positive results do not rule out bacterial infection, or co-infection with other viruses. The agent detected may not be the definite cause of disease. The use of additional laboratory testing (e.g. bacterial culture, immunofluorescence, radiography) and clinical presentation must be taken into consideration in order to obtain the final diagnosis of respiratory viral infection. Due to seasonal prevalence, performance characteristics for Influenza A/H1 were established primarily with retrospective specimens. The RVP assay cannot adequately detect Adenovirus species C, or serotypes 7a and 41. The RVP primers for detection of rhinovirus cross-react with enterovirus. A rhinovirus reactive result should be confirmed by an alternate method (e.g. cell culture). Performance characteristics for Influenza A Virus were established when Influenza A/H3 and A/H1 were the predominant Influenza A viruses in circulation. When other Influenza A viruses are emerging, performance characteristics may vary. If infections with a 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 a state or local health department for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.

Device Story

Multiplex nucleic acid assay; utilizes nasopharyngeal swab samples. Components: PCR primer mix, target-specific primer extension (TSPE) primers, coupled bead mix, buffer, and TDAS RVP-I software. Principle: Multiplex PCR amplification followed by TSPE and bead-based detection. Used in clinical laboratories by trained personnel. Software processes raw data to identify specific viral nucleic acids. Output aids clinicians in diagnosing respiratory viral infections; results must be correlated with clinical presentation and other laboratory tests. Benefits: Rapid simultaneous identification of multiple respiratory pathogens.

Clinical Evidence

Clinical performance evaluated during 2009 Influenza A/H1N1 outbreak. Study 1 (n=375): 201 samples Flu A positive; 141 unsubtypeable by RVP. CDC rRT-PCR confirmation of 101 unsubtypeable samples showed 99 positive for 2009 H1N1. Study 2 (n=2,715): 1,265 Flu A positive; 1,108 unsubtypeable by RVP, all confirmed as 2009 H1N1 via CDC rRT-PCR.

Technological Characteristics

Multiplex nucleic acid assay; includes PCR primer mix, TSPE primers, coupled bead mix, and analysis software. Detection via bead-based multiplexing. Software: TDAS RVP-I.

Indications for Use

Indicated for qualitative detection/identification of respiratory viral nucleic acids in nasopharyngeal swabs from patients suspected of respiratory tract infections. Targets: Influenza A (H1, H3), Influenza B, RSV (A, B), Parainfluenza 1-3, Human Metapneumovirus, Rhinovirus, Adenovirus. Not for sole diagnostic use; results must be interpreted with clinical/lab findings.

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

• xTAG® RVP (K063765)
• xTAG® RVP (K081483)

Submission Summary (Full Text)

{0}------------------------------------------------

K091667

# 510(k) Summary

## 1.0 Submitted By:

JUN 25 2009

Gloria Lee, Ph.D. Manager, Regulatory Affairs (Global Submissions) Luminex Molecular Diagnostics Inc. 439 University Ave. Toronto, Ontario M5G 1Y8 Canada Tel: [phone] x374 Fax: [phone] Email: [e-mail]

## 2.0 Date Submitted

June 3, 2009

## 3.0 Device Name(s):

Proprictary Name: xTAG® RVP Classification Name: Respiratory Viral Panel Multiplex Nucleic Acid Assay [866.3980]

## Legally Marketed Device 4.0

xTAG® RVP claims substantial equivalence to the xTAG® RVP originally cleared under FDA 510(k) k063765 and cleared under Special 510(k) k081483.

#### 5.0 Device Description

The xTAG Respiratory Viral Panel includes the following components:

- Multiplex PCR primer mix (without dNTPs) .
- Multiplex target specific primer extension (TSPE) primers (includes dNTPs) .
- Coupled bead mix .
- 10x buffer �
- xTAG® Data Analysis Software (TDAS RVP-I) .

## 6.0 Intended Use

The xTAG Respiratory Viral Panel (RVP) is a qualitative nucleic acid multiplex test intended for the simultaneous detection and identification of multiple respiratory virus nucleic acids in nasopharyngeal swabs from individuals suspected of respiratory tract infections. The following virus types and subtypes are identified using RVP: Influenza A. Influenza A subtype H1, Influenza A subtype H3, Influchza B, Respiratory Syncytial Virus subtype A, Respiratory Syncytial Virus subtype B, Parainfluenza 1, Parainfluenza 2, and Parainfluenza 3 virus. Human Metapneumovirus, Rhinovirus, and Adenovirus. The detection and identification of specific viral nucleic acids from individuals exhibiting signs and symptoms of respiratory infection aids in the diagnosis of respiratory viral infection if used in conjunction with other clinical and laboratory findings. It is recommended that specimens found to be negative for Influenza B, Respiratory Synctial Virus subtype A and B, Parainfluenza 2, Parainfluenza 3 and

{1}------------------------------------------------

Adenovirus, after examination using RVP be confirmed by cell culture. Negative results do not preclude respiratory virus infection and should not be used as the sole basis for diagnosis, treatment or other management decisions. Positive results do not rule out bacterial infection, or co-infection with other viruses. The agent detected may not be the definite cause of disease. The use of additional laboratory testing (e.g. bacterial culture, immunofluorescence, radiography) and clinical presentation must be taken into consideration in order to obtain the final diagnosis of respiratory viral infection.

Due to seasonal prevalence, performance characteristics for Influenza A/H1 were established primarily with retrospective specimens.

The RVP assay cannot adequately detect Adenovirus species C, or serotypes 7a and 41. The RVP primers for detection of thinovirus cross-react with enterovirus. A rhinovirus reactive result should be confirmed by an alternate method (e.g. cell culture).

Performance characteristics for Influenza A Virus were established when Influenza A/H3 and A/H1 were the predominant Influenza A viruses in circulation. When other Influenza A viruses are emerging, performance characteristics may vary. If infections with a 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 a state or local health department for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.

## Comparison to the Predicate (Description of the Modification to the Legally 7.0 Marketed Device)

The xTAG Respiratory Viral Panel performance parameters remain unchanged.

## Summary of Performance Data 8.0

The xTAG RVP can detect the matrix gene of 2009 Influenza A/H1N1 but can not identify the hemagglutinin gene of the 2009 Influenza A/H1N1 in clinical specimens. The studies summarized below demonstrate that xTAG RVP is an effective aid in the detection of 2009 influenza A/HIN1 strains (Ginocchio & George, 2009; Ginocchio et al. 2009):

In a study carried out during the 2009 Influenza A HINI (swine flu) outbreak in New York (Ginocchio & George, 2009), a total of 1,382 patient nasopharyngeal swab samples were initially tested with a variety of method including rapid antigen tests (n=1095), direct immunofluorescence (n=1164), and rapid virus culture (n=1140). Samples that tested positive for Influenza A with any of these methods, or derived from patients with a high potential to be infected with the 2009 Influenza A HINI strain, were further tested with xTAG RVP (n=375). A total of 201 of these samples were identified as Flu A positive by the RVP assay, two samples contained Influenza B, and other respiratory viruses in 58 samples (adenovirus, metapheumovirus. Parainfluenza 1. 2. 3. RSV, and rhinovirus). Sixty of the 201 Flu A positive samples were identified by xTAG RVP as seasonal strains (2 as H1 and 58 as H3). The remaining 14 Flu A positive samples were negative for both H1 and H3 by xTAG RVP (unsubtypeable). Frozen residual portions of 101 of the 141 unsubtypeable samples were forwarded to the Laboratory of Viral Diseases (Albany, NY) for further testing with the CDC rRT-PCR assay for 2009 Influenza A HINI (swine flu). A total of 99 of the 101 specimens tested with the CDC assay were identified as positive for 2009 Influenza A/H/N1 (CT<37). The two remaining specimens produced weak positive signals (CT>37) on one or more of the influenza targets and could not be classified as positive for the 2009 Influenza A/H/N/ strain. These two samples also produced weak positive signals in the RVP assay.

{2}------------------------------------------------

A study by Ginocchio et al. (2009) evaluated the performance of a variety of diagnostic assays, including the xTAG RVP, for the 2009 Influenza A/H1N1 surveillance. In this study, a total of 2,715 patient nasopharyngeal swab samples were tested by xTAG RVP and 1265 of these were positive for influenza A. Of the 1265, 1108 were "flu A unsubtypeable", 151 were seasonal H3N2 and 6 were seasonal H1N1. Of the 1108 flu A unsubtypeable with the xTAG RVP, all were confirmed to be Influenza A/H1N1 with the CDC rRT-PCR assay.

{3}------------------------------------------------

DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with three tail feathers, representing the three levels of government: federal, state, and local. The eagle is enclosed in a circle with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

# JUN 25 2009

Gloria Lee, Ph.D. Manager, Regulatory Affairs Luminex Molecular Diagnostics Inc. 439 University Avenue Suite 2000 Toronto, ON M5G 1Y8 Canada

Re: K091667 Trade/Device Name: xTAG® Respiratory Viral Panel Regulation Number: 21 CFR 866.3980 Regulation Name: Respiratory viral panel multiplex nucleic acid assay Regulatory Class: Class II Product Code: OCC,OEM,OEP Dated: June 3, 2009 Received: June 9, 2009

Dear Dr. Lee:

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. Ilsting 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 such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

{4}------------------------------------------------

## Page 2 -

This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at 240-276-0450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at 240-276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at 240-276-3464. 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/cdrh/industry/support/index.html.

Sincerely yours,

Sally attaym

Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

{5}------------------------------------------------

# Section 7.0 Indication for Use Statement

# 510(k) Number (if known): K091667 Device Name: xTAG® Respiratory Viral Panel Indication For Use:

The xTAG Respiratory Viral Panel (RVP) is a qualitative nucleic acid multiplex test intended for the simultaneous detection and identification of multiple respiratory virus nucleic acids in nasopharyngeal swabs from individuals suspected of respiratory tract infections. The following virus types are identified using RVP: Influenza A, Influenza A subtype H1, Influenza A subtype H3, Influenza B; Respiratory Syncytial Virus subtype A, Respiratory Syncytial Virus subtype B, Parainfluenza 1, Parainfluenza 2, and Parainfluenza 3 virus, Human Metapneumovirus, Rhinovirus, and Adenovirus. The detection and identification of specific viral nucleic acids from individuals exhibiting signs and symptoms of respiratory infection aids in the diagnosis of respiratory viral infection if used in conjunction with other clinical and laboratory findings. It is recommended that specimens found to be negative for Influenza B, Respiratory Synctial Virus subtype A and B, Parainfluenza 1, Parainfluenza 3 and Adenovirus, after examination using RVP be confirmed by cell culture. Negative results do not preclude respiratory virus infection and should not be used as the sole basis for diagnosis, treatment or other management decisions. Positive results do not rule out bacterial infection, or co-infection with other viruses. The agent detected may not be the definite cause of disease. The use of additional laboratory testing (e.g. bacterial culture, immunofluorescence, radiography) and clinical presentation must be taken into consideration in order to obtain the final diagnosis of respiratory viral infection.

Due to seasonal prevalence, performance characteristics for Influenza A/H were established primarily with retrospective specimens.

The RVP assay cannot adequately detect Adenovirus species C, or serotypes 7a and 41. The RVP primers for detection of rhinovirus cross-react with enterovirus. A rhinovirus reactive result should be confirmed by an alternate method (e.g. cell culture).

Performance characteristics for Influenza A Virus were established when Influenza A/H3 and A/H1 were the predominant Influenza A viruses in circulation. When other Influenza A viruses are emerging, performance characteristics may vary. If infections with a novel Influenza A virus is suspected based on current clinical and enidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent Influenza viruses and sent to a state or local health department for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.

Prescription Use X (21 CFR Part 801 Subpart D)

And/Or

Over the Counter Use (21 CFR Part 801 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)

Uwe Schuf

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety 1091661 510(k)