(142 days)
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.
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.
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.
Here's an analysis of the acceptance criteria and the study that proves the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria in terms of specific sensitivity and specificity thresholds. However, the conclusion states that the device was shown to be "substantially equivalent" to predicate devices, implying that its performance characteristics were deemed acceptable compared to established methods.
Here's a table summarizing the reported device performance in the clinical evaluation against the cultural gold standard for direct patient specimens:
| Type of Flu | Performance Metric | Site 1 | Site 2 |
|---|---|---|---|
| Influenza A | Sensitivity | 80.0% (95% CI: 61.4% to 92.3%) | 58.8% (95% CI: 32.9% to 81.6%) |
| Specificity | 98.6% (95% CI: 93.6% to 100%) | 98.3% (95% CI: 95.7% to 99.5%) | |
| Influenza B | Sensitivity | 50.0% (95% CI: 15.7% to 84.3%) | 43.2% (95% CI: 28.4% to 59.0%) |
| Specificity | 100% (95% CI: 96.7% to 100%) | 98.1% (95% CI: 95.1% to 99.5%) |
The document also provides performance relative to predicate devices for culture confirmation, which consistently show 97.8% to 100% sensitivity and 100% specificity for both Influenza A and B, suggesting the device performs very well in this context.
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set:
- Site 1: 147 specimens
- Site 2: 252 specimens
- Data Provenance: The data is from "clinical evaluation" using "patient specimens." The specific country of origin is not explicitly stated, but given the submission is to the FDA, it is highly likely to be the USA. The study design appears to be prospective or a cross-sectional study collecting current patient specimens for evaluation, as it compares the new device's results to a "culture confirmation" method for those specimens.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not specify the number or qualifications of experts involved in establishing the ground truth. It refers to "culture confirmation" as the gold standard. For laboratory culture, the interpretation would typically be done by trained laboratory personnel (e.g., medical technologists, microbiologists), but their specific qualifications or number are not detailed.
4. Adjudication Method for the Test Set
The document does not mention an adjudication method for the test set. Given that "culture confirmation" is used as the ground truth, it implies that the culture results themselves were considered definitive without needing further independent adjudication of the initial test results.
5. If a Multi-Reader, Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, a multi-reader, multi-case (MRMC) comparative effectiveness study was not done. This study focuses on the standalone performance of the immunofluorescence assay against a gold standard (culture) and in comparison to predicate devices, not on human reader performance with or without AI assistance.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, a standalone performance evaluation was done. The Light Diagnostics SimulFluor™ Flu A/Flu B Immunofluorescence Assay is a laboratory test, and its "performance characteristics" (sensitivity, specificity) were assessed directly. The "visualization with a fluorescence microscope" is a human-in-the-loop step, but the performance metrics are of the device (the reagent's ability to correctly stain infected cells) against the gold standard, implying a standalone evaluation of the diagnostic method itself, interpreted by a human.
7. The Type of Ground Truth Used
The primary ground truth used for the clinical evaluation was culture confirmation. This means that after initial testing, specimens were cultured to grow and identify the influenza virus, providing a definitive diagnosis against which the immunofluorescence assay's results were compared.
8. The Sample Size for the Training Set
The document does not specify a training set for the device. Immunofluorescence assays typically rely on the specificity of monoclonal antibodies rather than machine learning algorithms that require separate training and test sets. The "non-clinical evaluation" involving testing against various microorganisms and cell lines can be considered an initial validation or characterization, but not a "training set" in the machine learning sense.
9. How the Ground Truth for the Training Set Was Established
Since there is no explicit training set in the context of the device's development as described, the method for establishing its ground truth is not applicable. The "non-clinical evaluation" involved challenging the conjugated monoclonal antibodies with known viruses and bacteria, where the "ground truth" was the identity of the specific microorganism.
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K14502
APR - 8 1998
510(k) Summary
| Submitter: | Light Diagnostics28835 Single Oak DriveTemecula, CA 92590Tel: 909/676-8080Fax: 909/676-9209 |
|---|---|
| ------------ | ------------------------------------------------------------------------------------------------------------- |
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:
- 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.
- 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* | - |
| Bacteria | - |
| 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 | - |
| Cell Lines | - |
| RMK | - |
| MRC5 | - |
| AS49 | - |
| Vero | - |
- Slides obtained from Bion; for in vitro diagnostic use for serological assays
-
- 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.
- Clinical evaluation:
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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Image /page/5/Picture/2 description: The image shows the seal of the U.S. Department of Health and Human Services. The seal features an abstract design of an eagle with three tail feathers, symbolizing health, services, and people. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" are arranged in a circular pattern around the eagle.
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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Page 2
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 (770)488-7655.
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 (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. 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 (800) 638-2041 or at (301) 443-6597 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
§ 866.3330 Influenza virus serological reagents.
(a)
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.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9.