K Number
K041445
Date Cleared
2004-08-13

(73 days)

Product Code
Regulation Number
866.3480
Reference & Predicate Devices
Predicate For
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

ImmunoCard STAT!® RSV is a rapid, qualitative, lateral-flow immunoassay for the detection of Respiratory Syncytial Virus (RSV) antigens (fusion protein and internal protein) in human Nasal Wash, Nasopharyngeal Aspirate and Nasal and Nasopharyngeal Swab Samples. It is designed to test specimens from symptomatic neonatal and pediatric patients. It is recommended that all negative test results be confirmed by cell culture.

Device Description

ImmunoCard STAT! RSV is distributed as a test kit that includes the following reagents: ImmunoCard STAT! RSV Test Device: A chromatography strip housed in a plastic frame and enclosed in a foil pouch with a desiccant. The membrane carries immobilized monoclonal antibodies to RSV fusion and internal proteins at the TEST line and goat anti-mou nonotibordu at the CONTROL line. The strip also contains colloidal gold conjugated to monoconnal anti-RSV fusion protein and anti-RSV internal protein as the detector antibodies. Sample Diluent: A buffered protein solution containing sodium azide (0.095%) as a preservative. Positive Control: Inactivated RSV in a buffered solution containing sodium azide (0.095%) as a preservative.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study details for the ImmunoCard STAT! RSV device, based on the provided text:


1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly stated as distinct numerical targets (e.g., "Sensitivity must be >85%"). Instead, the study aims to demonstrate substantial equivalence to predicate devices, which implies that the device's performance should be comparable to or better than the predicates. The performance metrics presented below are directly from the clinical trials that serve as the basis for proving equivalence.

Performance MetricAcceptance Criteria (Implied by Predicate Equivalence)ImmunoCard STAT! RSV Reported Performance (Total Sites Combined, Resolved PCR Data)
Overall Agreement with Ground TruthComparable to predicate devices (e.g., Binax NOW RSV)92.1% (95% CI: 88.1% - 95.9%)
SensitivityComparable to predicate devices85.9% (95% CI: 78.0% - 94.0%)
SpecificityComparable to predicate devices96.3% (95% CI: 92.3% - 99.7%)
Positive Predictive Value (PPV)Comparable to predicate devices93.8% (95% CI: 88.3% - 99.7%)
Negative Predictive Value (NPV)Comparable to predicate devices91.2% (95% CI: 85.7% - 96.3%)

2. Sample Size Used for the Test Set and Data Provenance

  • Test Set Sample Size:

    • Total Samples (Combined Sites, unresolved): 174 (Table 6-5E)
    • Total Samples (Combined Sites, resolved against PCR data at Site 2): 178 (Table 6-5F)
    • Specific breakdown by sample type (resolved/unresolved not always distinct):
      • Wash/Aspirate (unresolved): 48 (28 positive, 20 negative by culture)
      • Wash/Aspirate (resolved): 52 (34 positive, 18 negative by culture)
      • Swab (unresolved): 126 (37 positive, 89 negative by culture)
  • Data Provenance: Retrospective and prospective. Samples were collected from symptomatic patients.

    • "archival (retrospective) or fresh (prospective) samples collected from symptomatic patients."
    • The study involved three independent clinical laboratories, implying data from different geographical locations, though specific countries are not mentioned beyond "USA alone" in the background section regarding RSV hospitalization statistics.

3. Number of Experts Used to Establish Ground Truth and Qualifications

The document does not specify the number of individual experts or their specific qualifications (e.g., "radiologist with 10 years of experience") for establishing the primary ground truth.

  • The ground truth methods used were tissue culture and PCR. These are laboratory-based diagnostic methods, not typically assessed by individual "experts" in the same way an image interpretation might be. The performance of these methods is inherent to the laboratory performing the assays, rather than a single individual's expertise. Clinical site 2 also performed PCR analysis for specimens with overgrowth in tissue culture or discrepant results, indicating a further analytical step by laboratory personnel.

4. Adjudication Method for the Test Set

  • Primary Adjudication: Clinical Site 2 performed PCR analysis on specimens that exhibited overgrowth in tissue culture or showed discrepant results between the immunoassay and initial tissue culture. This PCR data was then used to "correct" or resolve the initial tissue culture ground truth for those specific samples. This acts as an adjudication step specifically for cases where the primary ground truth (tissue culture) was problematic or led to discordance.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

  • No, an MRMC comparative effectiveness study was not done. This device is a diagnostic immunoassay (a rapid test for antigen detection), not an imaging device or algorithm requiring human interpretation. Therefore, assessing how human readers improve with AI assistance is not applicable. The comparison is between the device's performance and established laboratory reference methods (tissue culture, PCR).

6. Standalone Performance Study (Algorithm Only)

  • Yes, a standalone performance study was done. The entire clinical trial evaluates the ImmunoCard STAT! RSV device as a standalone diagnostic tool. Its performance (sensitivity, specificity, etc.) is directly compared against the established ground truth (tissue culture, sometimes resolved by PCR) without human interpretation as part of the device's output. The device itself produces a visual pink-red line for a positive result, and this is read directly.

7. Type of Ground Truth Used

  • Tissue Culture: This was the primary diagnostic test standard for RSV detection.
  • PCR (Polymerase Chain Reaction): Used as a secondary, confirmatory, or resolving ground truth for specific samples, particularly those with initial discrepant results or overgrowth in tissue culture.

8. Sample Size for the Training Set

  • Not explicitly stated. The document describes clinical trials for performance evaluation (test set) but does not provide details on a specific training set size or methodology for the development of the ImmunoCard STAT! RSV assay. Immunoassays typically rely on antibody development and binding characteristics, rather than a machine learning "training set" in the computational sense. The "training" in this context would likely refer to the iterative development and optimization of the assay components and parameters.

9. How the Ground Truth for the Training Set Was Established

  • Not explicitly described. As mentioned above, the concept of a "training set" with ground truth in the context of an immunoassay development differs from that of an AI algorithm. The development of the assay would have involved characterization of the monoclonal antibodies (directed at fusion and internal proteins of RSV) and optimization of the test device's chemical and physical properties to ensure reliable binding and signal generation. This process would inherently use characterized RSV samples (positive and negative) to establish optimal performance parameters, but these are not typically referred to as a "training set" with established "ground truth" in the same formal way as in AI/ML studies.

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K04-1445

ImmunoCard STAT! RSV

510(k) SUMMARY OF SAFETY AND EFFECTIVENESS

IDENTIFICATION INFORMATION

SUBMITTER'S INFORMATION

This summary of 510(k) safety and effectiveness is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.20.

SUBMITTER'S NAME AND ADDRESS: Meridian Bioscience, Inc. 3471 River Hills Drive Cincinnati, OH 45244

PHONE NUMBER: (513) 271-3700

FAX NUMBER: (513) 272-5213

CONTACT PERSON: Susan Rolih Vice President, Regulatory Affairs and Quality Assurance Official Correspondent

DATE SUMMARY PREPARED: August 5, 2004

NAME OF DEVICE: ImmunoCard STAT!® RSV

COMMON NAME: Reagent, Respiratory Syncytial Virus antigens

CLASSIFICATION NAME: Antigens, CF, Respiratory Syncytial Virus [83(GQG)]

REGULATION: 866.3480

INTENDED USES

ImmunoCard STAT!® RSV is a rapid, qualitative, lateral-flow immunoassay for the detection of Respiratory Syncytial Virus (RSV) antigens (fusion protein and internal protein) in human Nasal Wash, Nasopharyngeal Aspirate and Nasal and Nasopharyngeal Swab Samples. It is designed to test specimens from symptomatic neonatal and pediatric patients. It is recommended that all negative test results be confirmed by cell culture.

PREDICATE EQUIVALENT DEVICES:

ImmunoCard STAT! RSV is intended to detect the same analyte as other cleared devices including:

  • · Binax NOW® RSV [a rapid lateral-flow immunoassay cleared to market under 510(k) K032166] (Binax, Inc. South Portland, ME)
  • BD Directigen® EZ RSV [a rapid enzyme immunoassay cleared to market under 510(k) K022133J (Becton Dickinson & Co., Sparks, MD)

· RSV OIA® [an optical immunoassay cleared to market under 510(k) K023779] (Thermo-Biostar Inc., Louisville, CO)

BACKGROUND:

Respiratory Syncytial Virus (RSV) is the most important cause of pneumonia and bronchiolitis in infants and small children. Approximately 90,000 children are hospitalized each year due to RSV in the USA alone. Hospitalization due to RSV is more frequently associated with children that have underlying disease or premature birth. Mortality rates are estimated to be between 1 and 3% for children that are hospitalized with RSV.(1) RSV is also being recognized more frequently as a cause of significant

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respiratory disease in the elderly. RSV causes a wide range of respiratory symptoms that can be difficult to distinguish clinically from symptoms caused by other respiratory viruses such as influenza. Because of its high infectivity, the potential for prolonged patient shedding and the ability of the virus to survive for hours on environmental surfaces, RSV has emerged as a serious cause of nosomal infection. RSV can be detected in human respiratory samples by a variety of methods including tissue culture, immunofluorescent assay and enzyme immunoassay. Although tissue culture is still annsidered the diagnostic test standard, it requires tissue culture facilities and may take a week to complete. Immunofluorescent antibody-based tests are reasonably sensitive, yet highly dependent on specimen quality and preparation. Enzyme and microparticle-based immunoassays have become one the most frequently used methods for the detection of RSV. ImmunoCard STAT! RSV is a lateral from the nosed immunoassay for the rapid detection of RSV in human respiratory samples. The results from this test are used to support data available from the patient's clinical evaluation and assist the physician in determining a course of action.

Type of test

ImmunoCard STAT! RSV is a rapid, qualitative lateral-flow immunoassay screening test designed for use in clinical and doctor office laboratories.

Specimen type

The following specimens have been found compatible with ImmunoCard STAT! RSV.

  • Nasal wash 1.
    1. Nasopharyngeal aspirate
    1. Nasal and nasopharyngeal swabs

Conditions for use

ImmunoCard STAT! RSV is designed to be used under the normal environmental conditions existing in hospital and reference laboratories. The assay, which is stored at 2-8 C when not in use, is brought to room temperature prior to use. Normal laboratory lighting, humidity and temperature do not affect the performance of the assay.

Contraindications

There are no contraindications associated with the use of this product.

Special instrument requirements

No instruments are used with this product.

Combination with other medical devices

No other medical devices are used in combination with this device.

DEVICE DESCRIPTION AND TECHNOLOGICAL PRINCIPLES

Reagents

ImmunoCard STAT! RSV is distributed as a test kit that includes the following reagents:

ImmunoCard STAT! RSV Test Device: A chromatography strip housed in a plastic frame and enclosed in a foil pouch with a desiccant. The membrane carries immobilized monoclonal antibodies to RSV fusion and internal proteins at the TEST line and goat anti-mou nonotibordu at the CONTROL line. The strip also contains colloidal gold conjugated to monoconnal anti-RSV fusion protein and anti-RSV internal protein as the detector antibodies.

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Sample Diluent: A buffered protein solution containing sodium azide (0.095%) as a preservative.

Positive Control: Inactivated RSV in a buffered solution containing sodium azide (0.095%) as a preservative.

Equipment needed to use the device

There is no equipment needed to use this device.

Interfering substances

There are no known interfering substances that affect the performance of this device with the exception of whole blood at contaminating concentrations greater than 5%.

Calibrators

There are no calibrators used with this device.

Controls

The assay includes an internal CONTROL line that is used to demonstrate that sample has been applied, that it has flowed correctly and that the conjugated detector antibody is active at the time of testing. A clear, colorless background around the TEST and CONTROL. lines serves as a negative control and indicates that reagents were performing correctly at the time of use.

Positive Control Reagent and Sample Diluent (used for a negative control reagent) are supplied as external controls. These reagents also serve as indicators that the test was performed correctly, that the capture and detector antibodies were active at the time of use, and that the membrane supports proper sample flow.

Failure of the internal and external control to produce the expected results suggests the test was not performed correctly (ie, incorrect volume of reagents added; incorrect incubation temperature or times used or that reagents were not brought to room temperature prior to testing).

Technological principles

ImmunoCard STAT! RSV uses specific monoclonal antibodies directed at the fusion and internal proteins of RSV as the capture and detector antibodies are bound to the membrane of the Test Device at the reaction site marked TEST. Monoclonal anti-RSV fusion and anti-RSV internal protein antibodies are conjugated to colloidal gold and are suspended within the conjugate part. To perform the test, sample (nasal wash, nasopharyngeal aspirate, nasal and nasopharyngeal swabs) is first diluted with Sample Diluent, then added to the sample port of the Test Device. Antigens in the sample bind the conjugate detector antibodies as the sample migrates through the device. The RSVgold conjugate complexes will bind to the capture antibodies at the window site marked "Test" producing a visible pink-red line. In the absence of antigen, no pink-red line appears at this point.

Goat anti-mouse antibody is bound at the membrane site marked "Control". A visible pink-red line should appear at this position each time a sample or control reagent is tested. Failure to obtain a visible pink-red control line invalidates the test and is an indication of assay failure,

SUBSTANTIAL EQUIVALENCE TO PREDICATE DEVICES

The performance characteristics of ImmunoCard STAT! RSV were compared to several predicate devices. The comparison is shown in the next two tables.

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The predicate devices to which ImmunoCard STAT! RSV was compared are as follows: Binax NOW® RSV (Binax, Inc.) BD Directigen® EZ RSV (Becton Dickinson, Inc.) RSV OIA® (ThermoElectron Corp.)

CharacteristicsMeridianICSRSVBinax NOWRSVDirectigenEZ RSVThermobiostarRSV OIA®
Device Type
In vitro diagnostic deviceYesYesYesYes
ControlNoNoNoNo
CalibratorNoNoNoNo
Intended Use
Detection RSV in nasal samplesYesYesYesYes
Screening testYesYesYesYes
Diagnostic testNoNoNoNo
Monitoring therapyNoNoNoNo
Acceptable Sample
Nasal washYesYesYesYes
Nasopharyngeal aspirateYesNoYesYes
Nasal and nasopharyngeal swabsYesNoYesNo
Nasal wash or swab in transport mediumYesNoYesYes
Performance Characteristics (rounded) inMeridianBinax NOWDirectigenThermobiostar
Direct Comparison to Clinical Status orICSRSVRSVEZ RSVRSV OIA®
Condition
Sensitivity (wash/aspirate)23/28 (82%)88%76.9-87.2%86.8%
Sensitivity (swab)32/37 (87%)93%66.7-71.8%66.7%
Specificity (wash/aspirate)15/20 (75%)98%85.5-91.6%83.2%
Specificity (swab)86/89 (97%)93%95.0-91.6%96.4%
Predictive Value of a Positive Test (wash/aspirate)23/28 (82%)NDNDND
Predicate Value of a Positive Test (swab)32/35% (91%)NDNDND
Predictive Value of a Negative Test (wash/aspirate)15/20 (75%)NDNDND
Predicate Value of a Negative Test (swab)86/91 (95%)NDNDND
Agreement (wash/aspirate)38/48 (79%)93-96%NDND
Agreement (swab)118/126 (94%)NDNDND
Laboratory Equivalence with (Predicate(culture)(culture)(culture)(culture)
Device) combined totals
Concordance of positive tests with culture (wash/aspirate)23/28 (82%)45/51 (88%)NDND
Concordance of positive tests with culture (swab)32/37 (86%)NDNDND
Discordance of positive tests with culture (wash/aspirate)5/28 (18%)6/51 (12%)NDND
Discordance of positive tests with culture (swab)5/37 (14%)NDNDND
Concordance of negative tests with culture (wash/aspirate)15/20 (75%)196/199 (98%)NDND
Concordance of negative tests with culture (swab)86/89 (97%)NDNDND
Discordance of negative tests with culture (wash/aspirate)5/20 (25%)3/199 (2%)NDND
Discordance of negative tests with culture (swab)3/89 (3%)NDNDND
Performance characteristics
Precision/Reproducibility (intra-assay)94-100%100%99.1%95%
Precision/Reproducibility (inter-assay)100%100%99.1%95%
Linearity/reportable rangeN/AN/AN/AN/A
Limit of detection10-10,000 v/mL1.56 x 10⁴ - 5 x10⁴ TCID₅₀400-790 TCID501 x 10⁹ - 1 x10¹⁰⁹⁵% TCID₅₀
Assay cutoffN/AN/AN/AN/A

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CharacteristicICSRSVBinax NOW RSVBD Directogen EZ RSV
Intended useQualitative detection ofRSV in specimens fromneonatal and pediatricpatientsQualitative detection ofRSV in specimens frompediatric patientsQualitative detection ofRSV in specimens frompediatric patients
Specimen Required1. Nasal wash2. Nasopharyngealaspirate3. Nasal andnasopharyngeal swabs1. Nasal wash1. Nasal wash2. Nasal swab3. Nasopharyngealaspirate4. Nasopharyngeal swab5. sputum6. Tracheal aspirates7. Other swabs
TechnologyLateral flow, colloidal gold-based immunoassayLateral flow, colloidal gold-based immunoassayLateral flow, colloidal gold-based immunoassay
Level of skill requiredComplexity: ModerateCLIA waivedModerate complexity
Assay steps1. Add 4 drops sample diluent toa tube2. Add 150 uL sample and vortexto mix3. Add 150 uL diluted specimento Test Device.4. Incubate 15 min., 20-26 C.5. Read at end of incubation1. Add 100uL diluted specimen toTest Device.4. Incubate 15 min., 20-26 C.5. Read at end of incubation1. Add 3 drops sample diluent toa tube2. Add 250 uL sample and vortexto mix3. Add 3 drops diluted specimento Test Device.4. Incubate 15 min., 20-26 C.5. Read at end of incubation
End pointVisible pink-red lineVisible purple-pink lineVisible reddish purple
Interpretation of testresultPositive = appearance of pink-redtest and control lines (indicatedpresence of RSV antigens)Negative = no test line color withpink-red control line (indicatesabsence of RSV antigenPositive = appearance of purple-pink test and control lines(indicated presence of RSVantigens)Negative = no test line color withpurple -- pink control line (indicatesabsence of RSV antigenPositive = appearance of red-purple test and control lines(indicated presence of RSVantigens)Negative = no test line color withred-purple control line (indicatesabsence of RSV antigen

Comparison of Assay Methods

DEMONSTRATION OF EQUIVALENCE Clinical trials

Two independent laboratories and Meridian's Development Laboratory performed testing on archival (retrospective) or fresh (prospective) samples collected from symptomatic patients and that had been submitted because of a respiratory syndrome. Each laboratory tested the samples by its own reference method (if applicable), the predicate device Binax NOW RSV and ImmunoCard STAT! RSV.

Investigators were required to record the age and sex of the patient, and the type and age of each specimen at the time of testing, if available. Samples were tested fresh (stored at 2-8 C for no more than 72 hours) or after frozen storage at < -20 C.

Patient characteristics (patient age, sex) and sample type

Patient characteristics and sample characteristics are shown in the following tables. The age of the patients included in the clinical trial ranged from <1 to 71 years, and as expected, the majority of tests were performed on samples less than 6 years of age. Males and female patients were equally represented. Table 6-1 shows there were no significant differences in test results were no patient age or sample storage. Table 6-2shows patient sex had no affect on test results. Tables 6-3

absence of RSV antigen

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and 6-4 show there was no significant affect of sample source (or type), sample storage parameters or patient gender on test outcomes.

Table 6-1. Patient age, sample storage statistics and mean positive reaction strengths

Patient Age and Sample Storage<1 Yr.1-5 Yrs6-15 Yrs> 15 YrsNot defined
Clinical site 1
Total tested Fresh3612150
Mean positive reaction strength3.04.0No posNo posN/A
Positive reaction range1-64N/AN/AN/A
Total tested Frozen203000
Mean positive reaction strength3.61.0N/AN/AN/A
Positive reaction range1-71N/AN/AN/A
Clinical site 2
Total tested Fresh295000
Mean positive reaction strengthNot Recorded*Not RecordedN/AN/AN/A
Positive reaction rangeNot RecordedNot RecordedN/AN/AN/A
Total tested Frozen00000
Mean positive reaction strengthN/AN/AN/AN/AN/A
Positive reaction rangeN/AN/AN/AN/AN/A
Clinical site 3
Total tested Fresh00000
Mean positive reaction strengthN/AN/AN/AN/AN/A
Positive reaction rangeN/AN/AN/AN/AN/A
Total tested Frozen000068
Mean positive reaction strengthN/AN/AN/AN/A4.2
Positive reaction rangeN/AN/AN/AN/A0.5-9
Clinical site Totals
Total tested Fresh6517150
Mean positive reaction strength34No posNo posN/A
Positive reaction range1-64N/AN/AN/A
Total tested Frozen2030068
Mean positive reaction strength3.61N/AN/A4.2
Positive reaction range1-71N/AN/A0.5-9
Patient Age and Sample Storage<1 Yr.1-5 Yrs6-15 Yrs> 15 YrsNot defined

Site protocol did not require grading of reaction strengths.

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Table 6-2. Patient gender statistics and mean positive reaction strengths

MaleFemaleNot defined
Clinical site 1
Total tested47300
Mean positive reaction strength3.33.4N/A
Positive reaction range1-61-7N/A
Clinical site 2
Total tested24100
Mean positive reaction strengthNot RecordedNot RecordedN/A
Positive reaction rangeNot RecordedNot RecordedN/A
Clinical site 3
Total tested0068
Mean positive reaction strengthN/AN/A4.2
Positive reaction rangeN/AN/A0.5-9
Clinical site Totals
Total tested714068
Mean positive reaction strength3.33.44.2
Positive reaction range1-61-70.5-9

Table 6-3. Specimen sample type and mean positive reaction strengths

Specimen Type
SwabWashNPANot defined
Total tested -- Clinical Site 1
Total tested76100
Mean positive reaction strength3.42N/AN/A
Positive reaction range1-72N/AN/A
Total tested -- Clinical Site 2
Total tested03400
Mean positive reaction strengthN/ANot RecordedN/AN/A
Positive reaction rangeN/ANot RecordedN/AN/A
Total tested -- Clinical Site 3
Total tested500180
Mean positive reaction strength2.2N/A5N/A
Positive reaction range0.5-5N/A2-9N/A
Total tested - All Sites
Total tested12635180
Mean positive reaction strength3.225N/A
Positive reaction range0.5-722-9N/A

Legend: NPA = nasopharyngeal aspirate

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Table 6-4. Specimen sample storage parameters and mean positive reaction strengths

Specimen Type
FreshFrozenNot recorded
Total tested -- Clinical Site 1
Total tested54230
Mean positive reaction strength3.23.5N/A
Positive reaction range1-61-7N/A
Total tested -- Clinical Site 2
Total tested3400
Mean positive reaction strengthNot RecordedN/AN/A
Positive reaction rangeNot RecordedN/AN/A
Total tested -- Clinical Site 3
Total tested0680
Mean positive reaction strengthN/A4.2N/A
Positive reaction rangeN/A0.5-9N/A
Total tested -- All Sites
Total tested88910
Mean positive reaction strength3.23.9N/A
Positive reaction range1-60.5-9N/A

Clinical trial data summarized

The compiled results from clinical trials are summarized as follows:

Table 6-5. Results of clinical evaluations

6-5A

Clinical site 1ICS RSVBinax Now RSV
PosNegTotalPosNegTotal
Tissue Culture Pos3043427633
Tissue Culture Neg0434304343
Total304777274976
Concordant rate (%)Positive30/34 (88%)27/33 (82%)
Negative43/43 (100%)43/43 (100%)
Discordant rate (%)Positive4/34 (12%)6/33 (18%)
Negative0/43 (0%)0/43 (0%)
Agreement73/77 (94.8%)95% CI90.1% - 99.9%70/76 (92.1%)
Sensitivity30/34 (88.2%)77.0%-99.0%27/33 (81.8%)
Specificity43/43 (100%)N/A43/43 (100%)
Predictive value positive test30/30 (100%)N/A27/27 (100%)
Predictive value negative test43/47 (91.5 %)82.8% - 99.2%43/49 (87.8 %)

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6-5B

Clinical site 2ICS RSVBinax Now RSV
PosNegTotalPosNegTotal
Tissue Culture Pos729729
Tissue Culture Neg5152051520
Total121729121729
Concordant rate (%)
Positive7/9 (78%)7/9 (78%)
Negative15/20 (75%)15/20 (75%)
Discordant rate (%)
Positive2/9 (22%)2/9 (22%)
Negative5/20 (25%)5/20 (25%)
95% CI
Agreement22/29 (75.9%)60.5% - 91.5%22/29 (75.9%)
Sensitivity7/9 (77.8%)51.0% - 100%7/9 (77.8%)
Specificity15/20 (75.0%)56.0% - 94.0%15/20 (75.0%)
Predictive value positive test7/12 (58.3%)30.2% - 85.8%7/12 (58.3%)
Predictive value negative test15/17 (88.2%)72.5% - 100%15/17 (88.2%)

Clinical Site 2 performed PCR analysis on specimens that exhibited overgrowth in tissue culture or discrepant results between Immune on spesiments that cannines overyown in Insure of indicated that culture results were falsely ne 77th . Test results are recalculated based on the PCR data and given in table immediately hegative. Test results are matched to individual samples in Table 6-6.

6-5C
Clinicalsite 2 dataAFTERcorrection to PCR resultsICS RSVBinax Now RSV
PosNegTotalPosNegTotal
Tissue Culture Pos1321513215
Tissue Culture Neg1171811718
Total141933141933
Concordant rate (%)
Positive13/15 (87%)13/15 (87%)
Negative17/18 (94%)17/18 (94%)
Discordant rate (%)
Positive2/15 (13%)2/15 (13%)
Negative1/18 (6%)1/18 (6%)
95% CI
Agreement30/33 (90.9%)81.2% - 100%30/33 (90.9%)
Sensitivity13/15 (86.7%)70.0% - 100%13/15 (86.7%)
Specificity17/18 (94.4%)83.0% - 100%17/18 (94.4%)
Predictive value positive test13/14 (92.9 %)79.7% - 100%13/14 (92.9 %)
Predictive value negative test17/19 (89.5%)74.9% - 100%17/19 (89.5%)

e-SD

Clinical site 3ICS RSVBinax Now RSV
PosNegTotalPosNegTotal
Tissue Culture Pos1842217421
Tissue Culture Neg3434604646
Total214768175067
Concordant rate (%)
Positive18/22 (82%)17/21 (81%)
Negative43/46 (93%)46/46 (100%)
Discordant rate (%)
Positive4/22 (18%)4/21 (19%)
Negative3/46 (7%)0/46 (0%)
95% CI
Agreement61/68 (89.7%)82.9% - 97.1%63/67 (94.0%)
Sensitivity18/22 (81.8%)65.9% - 98.1%17/21 (81.0%)
Specificity43/46 (93.5%)85.6% - 100%46/46 (100%)
Predictive value positive test18/21 (85.7%)71.1% - 100%17/17 (100%)
Predictive value negative test43/47 (91.5%)82.8% - 99.2%46/50 (92.0%)

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6-5E

Total Sites Combined Data - Comparison to StandardICS RSV
PosNegTotal
Tissue Culture Pos551065
Tissue Culture Neg8101109
Total63111174
Concordant rate (%)
Positive55/65 (85%)
Negative101/109 (93%)
Discordant rate (%)
Positive10/65 (15%)
Negative8/109 (7%)
95% CI
Agreement156/174 (89.7%)88.1% - 94.5%
Sensitivity55/65 (84.6%)76.4% - 93.6%
Specificity101/109 (92.7%)88.3% - 97.7%
Predictive value positive test55/63 (87.3%)78.8% - 95.2%
Predictive value negative test101/111 (91.0%)85.7% - 96.3%

e-5E

Total Sites Combined Data - Comparison to Standard resolved againstPCR data at Site 2.ICS RSV
PosNegTotal
Tissue Culture Pos611071
Tissue Culture Neg4103107
Total65113178
Concordant rate (%)
Positive61/71 (86%)
Negative103/107 (96%)
Discordant rate (%)
Positive10/71 (14%)
Negative4/107 (4%)
95% CI
Agreement164/178 (92.1%)88.1% - 95.9%
Sensitivity61/71 (85.9%)78.0% - 94.0%
Specificity103/107 (96.3%)92.3% - 99.7%
Predictive value positive test61/65 (93.8%)88.3 % - 99.7%
Predictive value negative test103/113 (91.2%)85.7% - 96.3%

Characterization of samples producing discordant results

The data collected during clinical trials is shown in the spreadsheets provided at the end of these sections. The results can be summarized as follows:

SampleNumberICS RSVResultsCulture ResultsCommentsPCR Results
1-4NegRSVFNNo repeat testing performed
1-56NegRSVFNNo repeat testing performed
1-57NegRSVFNNo repeat testing performed
1-61NegRSVFNNo repeat testing performed
2-21NegOvergrownOvergrownNeg
2-27PosOvergrownOvergrownPos RSV A
2-41NegRSVFNNeg
2-42PosNegFPPos RSV A
2-44PosOvergrownOvergrownPos RSV A
2-45PosNegFPPos RSV A& B
2-46PosNegFPPos RSV A
2-59NegRSVFNNo repeat testing performed
2-69NegOvergrownOvergrownPos RSV A
2-70PosOvergrownOvergrownEquivocal
2-72PosNegFPNeg
2-73PosNegFPPos RSV A
3-7NegRSVFNNo repeat testing performed
3-18Pos 0/1Para 3FPNeg
3-32Pos 1NegFPNeg
3-39Pos 1NegFPNeg
3-62NegRSVFNNo repeat testing performed
3-64NegRSVFNNo repeat testing performed
3-67NegRSVFNNo repeat testing performed

Table 6-6. Samples producing discrepant results.

Legend: ICS RSV = ImmunoCard STAT! RSV, FN = false negative, FP = false positive

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The following data sets given in Table 6-7 provide analysis of clinical data by sample type (wash/aspirate vs swab). The data in these tables show there is no significant differences in outcomes of tests performed with wash, aspirate or swab samples.

Table 6-7. Results of comparison to predicate device

6-7A

Wash/Aspirate SpecimensNot resolvedICS RSVBinax Now RSV
PosNegTotalPosNegTotal
Tissue Culture Pos2352822527
Tissue Culture Neg5152051520
Total282048272047
Concordant rate (%)
Positive23/28 (82%)22/27 (81%)
Negative15/20 (75%)15/20 (75%)
Discordant rate (%)
Positive5/28 (18%)5/27 (19%)
Negative5/20 (25%)5/20 (25%)
Agreement38/48 (79.2%)37/47 (78.7%)
67.2% - 90.8%
Sensitivity23/28 (82.1%)22/27 (81.5%)
68.3% - 95.7%
Specificity15/20 (75.0%)15/20 (75.0%)
55.4% - 94.6%
Predictive value positive test23/28 (82.1%)22/27 (81.5%)
68.3% - 95.7%
Predictive value negative test15/20 (75.0%)15/20 (75.0%)
55.4% - 94.6%

Note to table above: 5 overgrown specimens not included, 1 QNS to run on Binax

6-7B

Wash/Aspirate SpecimensResolvedICS RSVBinax Now RSV
PosNegTotalPosNegTotal
Tissue Culture Pos2953428533
Tissue Culture Neg1171811718
Total302252292251
Concordant rate (%)
Positive29/34 (85%)28/33 (85%)
Negative17/18 (94%)17/18 (94%)
Discordant rate (%)
Positive5/34 (15%)5/33 (15%)
Negative1/18 (6%)1/18 (6%)
Agreement46/52 (88.5%)78.2% - 97.8%45/51 (88.2%)
Sensitivity29/34 (85.3%)73.2% - 96.8%28/33 (84.8%)
Specificity17/18 (94.4%)82.2% - 100%17/18 (94.4%)
Predictive value positive test29/30 (96.7%)91.1% - 100%28/29 (96.6%)
Predictive value negative test17/22 (77.3%)17/22 (77.3%)

Note to table above: 1 QNS to run on Binax, 1 Equivocal Specimen after PCR

6-7C

Swab SpecimensICS RSVBinax Now RSV
PosNegTotalPosNegTotal
Tissue Culture Pos3253729736
Tissue Culture Neg3868908989
Total35911262996125
Concordant rate (%)
Positive32/37 (86%)29/36 (81%)
Negative86/89 (97%)89/89 (100%)
Discordant rate (%)
Positive5/37 (14%)7/36 (19%)
Negative3/89 (3%)0/89 (0%)
Agreement118/126 (93.7%)118/125 (94.4%)
Sensitivity32/37 (86.5%)74.2% - 97.8%29/36 (80.6%)
Specificity86/89 (96.6%)93.1% - 100%89/89 (100%)
Predictive value positive test32/35 (91.4%)81.2% - 100%29/29 (100%)
Predictive value negative test86/91 (94.5%)90.1% - 97.9%89/96 (92.7%)

Note to table above: 1 Binax Invalid Result, No resolved data. PCR was negative for the 3 false positive samples

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Reproducibility

Two reproducibility panels, each consisting of eight coded specimens, were sent to the three clinical sites. Five of these samples in each set were classified by the predicate device Binax NOW RSV as positive. One additional sample was at the limit of detect of ImmunoCard STAT! RSV. The samples were expected to produce a positive or negative result. Even though the trial sites were instructed to grade reactions, there were no criteria regarding the strength of a positive reaction that was expected. Tables 6-8 show that all samples in Panel 1 and 7/8 samples in Panel 2 demonstrated intra- and inter-assay reproducibility of 100%. One sample (Panel 2) gave a reproducible rate of 94%.

Clinical Site 3Clinical Site 1Clinical Site 2
Sample IDDay 1Day 2Day 3Day 1Day 2Day 3Day 1Day 2Day 3
1 LP521121222
2 LP34.55223312
3 MP655.5342334
4 MP112222111
5 HP768466565
6 N000000000
7 N000000000
8 Limit of detect000000000
Total positive score2218.521.5121614141314
Average positive score4.43.74.32.43.22.82.82.62.8
Percent correlation100100100100100100100100100

Table 6-8. Results with reproducibility test panel #1

Legend: LP = low positive, MP = moderate positive, HP = high positive, N = negative,

Clinical Site 1Clinical Site 2Clinical Site 3
Sample IDDay 1Day 2Day 3Day 1Day 2Day 3Day 1Day 2Day 3
1 LP1410111.521
2 LP464344144
3 MP4445636.557
4 MP565564776.5
5 HP511376897
6 N000000000
7 N000000000
8 Limit of detect0001001.518
Total positive score192115162418242725.5
Average positive score3.84.23.03.24.83.64.85.45.1
Percent correlation10010010087.5100100100100100

Table 6-9. Results with reproducibility test panel #2

Legend: LP = low positive, MP = moderate positive, HP = high positive, N = negative,

High dose hook effect

There was no high dose hook effect observed in verification or clinical testing performed with this assay.

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CONCLUSIONS

ImmunoCard STAT! RSV:

  • Can be used reliably for the rapid detection of RSV antigens in human respiratory samples. 1.
    1. Performs similarly to the predicate device Binax NOW RSV.
ICS RSVNOW RSV
PosNegTotalPosNegTotal
Culture Pos551065511263
Culture Neg81011095104109
Total6311117456116172
Concordance rate (% to culture)
Positive55/65 (85%)51/63 (81%)
Negative101/109 (93%)104/109 (95%)

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/13/Picture/1 description: The image shows the logo for the Department of Health & Human Services USA. The logo features a stylized eagle with three stripes forming its body and wing. The eagle is facing right. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular fashion around the eagle.

Public Health Service

AUG 1 3 2004

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Susan Rolih Vice President, Regulatory Affairs/Quality Assurance Meridian Bioscience, Inc. 3471 River Hills Drive Cincinnati, OH 45244

Re: K041445

Trade/Device Name: Immuno Card STAT! RSV Regulation Number: 21 CFR 866.3480 Regulation Name: Respiratory Syncytial Virus Serological Reagents Regulatory Class: Class I Product Code: GQG Dated: May 28, 2004 Received: June 10, 2004

Dear Ms. Rolih:

We have reviewed your Section 510(k) premarket notification of intent to market the device wt nave reviewed your bected. or substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate for use stated in the enactment date of the Medical Device Amendments, or to conninered processified 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). and Cosmetic (1 to (1 to ) that the device, subject to the general controls provisions of the Act. The 1 ou may, incresere, mass 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 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 nav 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 that I Dr Has Intactions and regulations administered by other Federal agencies. You must or any I catal statutes and enginements, 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).

{14}------------------------------------------------

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 information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). 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) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Salamatys

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

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Meridian Bioscience, Inc. Cincinnati, OH

510(k) Notification ImmunoCard STAT! RSV

INDICATIONS FOR USE STATEMENT ImmunoCard STAT! RSV

510(K) Number: K041445

ImmunoCard STAT! RSV is a rapid, qualitative, lateral-flow immunoassay for the detection of Intribution Syncytial Virus (RSV) antigens (fusion protein or internal protein) in human nasal wash, nasophary Gyhoylar Viras (1107) anigene nasopharyngeal swab samples. It is designed to test hasophalyngear aspirate and naddr and necopial yngoal of is recommended that all negative test results be confirmed by cell culture.

Prescription Use _____________________________________________________________________________________________________________________________________________________________ (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use _ (21 CFR 807 Subpart C)

Division Sign Off
Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Office of In Vitro Diagnostic Device Evaluation and Safety

510(%) . _ K204 144 S

Tab 8, Page 1

§ 866.3480 Respiratory syncytial virus serological reagents.

(a)
Identification. Respiratory syncytial virus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to respiratory syncytial virus in serum. Additionally, some of these reagents consist of respiratory syncytial virus antisera conjugated with a fluorescent dye (immunofluorescent reagents) and used to identify respiratory syncytial viruses from clinical specimens or from tissue culture isolates derived from clinical specimens. The identification aids in the diagnosis of respiratory syncytial virus infections and provides epidemiological information on diseases caused by these viruses. Respiratory syncytial viruses cause a number of respiratory tract infections, including the common cold, pharyngitis, and infantile bronchopneumonia.(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 § 866.9.