LIGHT DIAGNOSTICS SIMULFLUOR FLU A/FLU B

K974302 · Light Diagnostics · GNW · Apr 8, 1998 · Microbiology

Device Facts

• Record ID: K974302
• Device Name: LIGHT DIAGNOSTICS SIMULFLUOR FLU A/FLU B
• Applicant: Light Diagnostics
• Product Code: GNW · Microbiology
• Decision Date: Apr 8, 1998
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3330
• Device Class: Class 1

Indications for Use

The Light Diagnostics SimulFluor™ Flu A/Flu B Immunofluorescence Assay is intended for the detection and identification of influenza A and influenza B in respiratory specimens such as throat, nasal and nasopharyngeal swabs, nasopharyngeal aspirates, broncho-alveolar lavages from patients with febrile respiratory illness and following amplification of virus in cell culture. Specimens found to be negative on direct specimen examination must be confirmed with culture. For in vitro diagnostic use.

Device Story

Assay uses single reagent containing monoclonal antibodies specific to influenza A nucleoprotein and influenza B nucleoprotein; antibodies labeled with distinct fluorescent markers. Input: respiratory specimens (swabs, aspirates, lavages) or cell culture isolates. Process: reagent binds to viral antigens; unbound reagent rinsed with PBS; complexes visualized via fluorescence microscopy. Output: apple-green fluorescence for influenza A; yellow-gold for influenza B; dull red for uninfected cells (Evans blue counterstain). Used in clinical laboratories by trained personnel. Enables rapid identification of influenza A/B; assists clinicians in diagnosis and management of febrile respiratory illness. Single-well detection replaces need for separate wells required by predicate kits.

Clinical Evidence

Clinical evaluation compared subject device to culture confirmation and predicate reagents. Study 1 (n=147): Sensitivity 80.0% (Flu A), 50.0% (Flu B); Specificity 98.6% (Flu A), 100% (Flu B) vs culture. Study 2 (n=252): Sensitivity 58.8% (Flu A), 43.2% (Flu B); Specificity 98.3% (Flu A), 98.1% (Flu B) vs culture. Comparison to Bartels reagents showed high concordance (97.8-100% sensitivity, 100% specificity). Non-clinical testing confirmed specificity against various respiratory viruses and bacteria.

Technological Characteristics

Direct immunofluorescence assay. Reagent contains monoclonal antibodies conjugated with two different fluorescent labels. Employs Evans blue counterstain. Visualized via fluorescence microscope. Requires phosphate-buffered saline (PBS) for rinsing. In vitro diagnostic use.

Indications for Use

Indicated for detection and identification of influenza A and B in patients with febrile respiratory illness. Specimens include throat, nasal, nasopharyngeal swabs, nasopharyngeal aspirates, and broncho-alveolar lavages. Negative direct specimen results require culture confirmation.

Regulatory Classification

Identification

Influenza virus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to influenza in serum. The identification aids in the diagnosis of influenza (flu) and provides epidemiological information on influenza. Influenza is an acute respiratory tract disease, which is often epidemic.

Predicate Devices

• BARTELS Influenza A and B Reagents
• DAKO IMAGEN Influenza Virus A and B

Reference Devices

• Light Diagnostics Respiratory Virus Panel I IFA

Submission Summary (Full Text)

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K14502

APR - 8 1998

## 510(k) Summary

| Submitter: | Light Diagnostics<br>28835 Single Oak Drive<br>Temecula, CA 92590<br>Tel: [phone]<br>Fax: [phone] |
|------------|-------------------------------------------------------------------------------------------------------------|
|------------|-------------------------------------------------------------------------------------------------------------|

Contact Person: Cindy Penny

## Product Name:

Trade Name: Light Diagnostics SimulFluor™ Flu A/Flu B Common Name: Immunofluorescence Assay Classification Name: Influenza virus Classification Number: 866.3330

## Intended Use:

The Light Diagnostics SimulFluor™ Flu A/Flu B Immunofluorescence Assay is intended for the detection and identification of influenza A and influenza B in respiratory specimens such as throat, nasal and nasopharyngeal swabs, nasopharyngeal aspirates, broncho-alveolar lavages from patients with febrile respiratory illness and following amplification of virus in cell culture. Specimens found to be negative on direct specimen examination must be confirmed with culture.

For in vitro diagnostic use.

# Predicate Devices:

1) BARTELS Influenza A and B Reagents

The Bartels Influenza A and B reagents are part of the Viral Respiratory Screening and Identificaton Kit. The reagents are intended for the detection of influenza A and B viruses in direct specimen and for culture confirmation. For in vitro diagnostic use.

2) DAKO IMAGENTM Influenza Virus A and B

The IMAGEN™ Influenza virus A and B test is a qualitative direct immunofluorescence test for the detection and differentiation of Influenza A virus and Influenza B virus in clinical samples or for the confirmation and differentiation of Influenza virus A and B in cell cultures. For in vitro diagnostic use.

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## Device description:

Light Diagnostics SimulFluor™ Flu A/Flu B Immunofluorescence Assay utilizes a single reagent for the simultaneous detection and identification of influenza A and influenza B. The primary component, specific for influenza A, will bind to influenza A nucleoprotein in influenza A-infected cells. The secondary component, specific for influenza B, will bind to influenza B nucleoprotein in influenza B-infected cells. Unbound reagent is removed by rinsing with phosphate-buffered saline (PBS). The complexes are visualized with a fluorescence microscope. The influenza A antigenantibody complex will exhibit an apple-green fluorescence and the influenza B antigenantibody complex will be yellow-gold. Uninfected cells stain a dull red due to the presence of Evans blue in the reagent.

antibodies ensures increased specificity of the reagent and reduces the risk of non-specific background or interference.

# Technological Comparison of Methods:

The Light Diagnostics SimulFluor™ Flu A/Flu B Immunofluorescence Assay is substantially equivalent to DAKO IMAGEN Influenza Virus A and B and Bartels Influenza A and B reagents:

- A. All three methods are intended for use in the detection of influenza A and influenza B antigens in patient specimens and infected cells.
- B. All three methods are in vitro test methods.
- C. All three methods use a direct immunofluorescence assay procedure for staining of slides.

The methods differ in that:

- A. The Light Diagnostics SimulFluor™ Flu A/Flu B Immunofluorescence Assay contains only one reagent which contains specific monoclonal antibodies labeled with two different fluorescent labels. This allows visualization of both viruses in one well, whereas hoth DAKO and BARTELS kits contain two separate reagents, each of which contains FITC-labeled monoclonal antibodies directed against either influenza A or B. Two separate wells are necessary to detect both viruses in one sample.
Performance Data for Light Diagnostics SimulFluor™ Flu A/Flu B Immunofluorescence Assay:

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- I. Non-clinical evaluation:
With the exception of one monoclonal antibody to influenza B (clone 22D), the monoclonal antibodies used in this reagent are identical to those used in the Influenza A and Influenza B reagents that are part of the Light Diagnostics Respiratory Virus Panel I IFA, cleared for in vitro diagnostic use.

The conjugated monoclonal antibodies used in the SimulFluor™ Flu A/Flu B reagent were tested against a variety of viruses and bacteria found in the respiratory tract, and cell lines commonly used to isolate influenza A and B viruses. The results are indicated in the table below.

| Microorganisms | SimulFluorTM Flu A/B |
|-----------------------------------------------|----------------------|
| Viruses | |
| Adenovirus: AD-75 CDC V5-002 | - |
| Coxsackievirus A9; ATCC VR-186 | - |
| Coxsackievirus B1; NIH | - |
| Cytomegalovirus; clinical isolate | - |
| Enterovirus 70; ATCC VR-836 | - |
| Enterovirus 71; ATCC VR-784 | - |
| Echovirus 4; ATCC VR-34 | - |
| Echovirus 6; ATCC VR-36 | - |
| Echovirus, 9; ATCC VR-39 | - |
| Echovirus 11; ATCC VR-41 | - |
| Echovirus 30; ATCC VR-322 | - |
| Herpes simplex virus type 1; clinical isolate | - |
| Herpes simplex virus type 2; clinical isolate | - |
| Influenza A: | |
| H1N1: 6 strains | + |
| H2N2: 1 strain | + |
| H3N2: 8 strains | + |
| Influenza B; 6 strains | + |
| Mumps; | - |
| Measles | - |
| Parainfluenza 1; CDC V6-004 | - |
| Parainfluenza 2; CDC V7-003 | - |
| Parainfluenza 3; CDC V5-003 | - |
| Parainfluenza 4A; VR1378 Strain M-25 | - |
| Respiratory syncytial virus; clinical isolate | - |
| Pneumocystis carinii, rat lung | - |
| Varicella zoster virus; clinical isolate | - |

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| Microorganisms | SimulFluorTM Flu A/B |
|------------------------------------------------|----------------------|
| Parainfluenza 1: CDC V6-004 | - |
| Parainfluenza 2; CDC V7-003 | - |
| Parainfluenza 3; CDC V5-003 | - |
| Parainfluenza 4A; VR1378 Strain M-25 | - |
| Respiratory syncytial virus: clinical isolate* | - |
| PCP; rat derived | - |
| Varicella zoster virus; clinical isolate* | - |
| <b>Bacteria</b> | - |
| Bordetella bronchiseptica; ATCC 10580 | - |
| Bordetella pertussis; ATCC 9340 | - |
| Branhamella catarrhalis; ATCC 25238 | - |
| Chlamydia trachomatis; ATCC | - |
| Chlamydia pneumoniae | - |
| Corynebacterium diphtheriae; ATCC 13812 | - |
| Legionella micdadei; ATCC 33204 | - |
| Legionella pneumophila; ATCC 33156 | - |
| Mycobacterium tuberculosis; ATCC 25177 | - |
| Mycoplasma hominis; ATCC 23114 | - |
| Mycoplasma pneumoniae; ATCC 15531 | - |
| Neisseria meningitidis; ATCC 13077 | - |
| <b>Cell Lines</b> | - |
| RMK | - |
| MRC5 | - |
| AS49 | - |
| Vero | - |

* Slides obtained from Bion; for in vitro diagnostic use for serological assays

- 2. Clinical evaluation:
The Light Diagnostics SimulFluor™ Flu A/Flu B Immunofluorescence Assay was compared in clinical evaluation to culture confirmation for the detection and identification of influenza A and B viruses and patient specimens. The SimulFluor™ Flu A/Flu B was compared to the Bartels Influenza A and Influenza B reagents, and the Dako IMAGEN Influenza Virus A and B reagents for the detection and identification of influenza A and B viruses following isolation in culture.

One hundred and forty-seven specimens were evaluated at Site 1. On patient specimens the SimulFluor™ Flu A/Flu B reagent had a sensitivity of 80.0% (95% Confidence Interval of 61.4% to 92.3%) and a specificity of 98.6% (95% Confidence Interval of 93.6% to 100%) compared to culture for the identification

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of influenza A and a sensitivity of 50.0% (95% Confidence Interval of 15.7% to 84.3%) and a specificity of 100% (95% Confidence Interval of 96.7% to 100%) compared to culture for the identification of influenza B.

When compared to Bartels Influenza A and B reagents for culture confirmation, the Light Diggnostics SimulFluor™ Flu A/Flu B Immunofluorescence Assay had a sensitivity of 97.8% (95% Confidence Interval of 93.8% to 100%) and a specificity of 100% (95% Confidence Interval of 96.4% to 100%) for influenza A and a sensitivity of 100% (95% Confidence Interval of 75.3% to 100%) and a specificity of 100% (95% Confidence Interval of 97.3% to 100%) for influenza B.

Two hundred and fifty-two specimens were evaluated at Site 2. On patient specimens the SimulFluor™ Flu A/Flu B reagent had a sensitivity of 58.8% (95% Confidence Interval of 32.9% to 81.6%) and a specificity of 98.3% (95% Confidence Interval of 95.7% to 99.5%) compared to culture for the identification of influenza A and a sensitivity of 43,2% (95% Confidence Interval of 28.4% to 59.0%) and a specificity of 98.1% (95% Confidence Interval of 95.1% to 99.5%) compared to culture for the identification of influenza B.

When compared to Bartels Influenza A and B reagents for culture confirmation, the Light Diagnostics SimulFluor™ Flu A/Flu B Immunotluorescence Assay had a sensitivity of 100% (95% Confidence Interval of 79.4% to 100%) and a specificity of 100% (95% Confidence Interval of 98.4% to 100%) for influenza A and a sensitivity of 100% (95% Confidence Interval of 92.6% to 100%) and a specificity of 100% (95% Confidence Interval of 98.2% to 100%) for influenza B.

## 3. Conclusions drawn from evaluations:

Light Diagnostics SimulFluor™ FJu A/Flu B Immunofluorescence Assay uses a standard direct immunofluorescence assay procedure for the detection of influenza A and B viruses in patient specimens and in cell culture. The monoclonal antibodies used in the reagent have been characterized so as to ensure specificity and reliability of the product. In clinical evaluations, the performance characteristics of the reagent was shown to be substantially equivalent to those of Bartels Influenza A and Influenza B reagents and Dako IMAGEN Influenza Virus A and B.

The characterization and clinical evaluation of the Light Diagnostics SimulFluor™ Flu A/Flu B Immunofluorescence Assay demonstrates the safety and effectiveness of this product when used as intended, as described in the product insert.

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APR - 8 1900 Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Cindy D. Penny Quality Assurance Manager Light Diagnostics 28835 Single Oak Drive Temecula, CA 92590

Re: K974302 Trade Name: Light Diagnostics SimulFluor Flu A / Flu B Regulatory Class: I Product Code: GNW Dated: February 4, 1998 Received: February 5, 1998

Dear Ms. Penny:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we 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). 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 (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (OS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.

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Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at [phone].

This letter will allow you to begin marketing your device as described in your 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 vour device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at [phone]. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll free number [phone] or at [phone] or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"

Sincerely yours,

Steven Sutman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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K974302 510(k) Number (if known):

Device Name: Light Diagnostics SimulFluor™ Flu A/Flu B Immunofluorescence Assav

SimulFluor™ Flu A/Flu The Light Diagnostics в Indications For Use: Immunofluorescence Assay is intended for the detection and identification of influenza A and influenza B in respiratory specimens such as throat, nasal and nasopharyngeal swabs, nasopharyngeal aspirates, broncho-alveolar lavages from patients with febrile respiratory illness and following amplification of virus in cell culture. Specimens found to be negative on direct specimen examination must be confirmed with culture. For in vitro diagnostic use.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use (Per 21 CFR 801.109)

Over-The-C

Over-The-Counter-Use

R. Kent

(Optional Format 1-2-96)

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number. K974302

OR