TRU RSV is a rapid, qualitative, lateral-flow immunoassay for the detection of Respiratory Syncytial Virus (RSV) antigens (fusion protein or nucleoprotein) in human nasal wash, nasopharyngeal aspirate, and nasal and nasopharyngeal swab samples. It is designed to test specimens from symptomatic patients aged 5 years or less. A negative result does not preclude RSV infection. It is recommended that all negative test results be confirmed by cell culture.

Device Description

TRU RSV is a rapid, single-use, qualitative lateral-flow immunoassay screening test. The test kit includes a Test Strip attached to a plastic frame or holder, a Conjugate Tube containing a lyophilized bead of colloidal gold-linked monoclonal antibodies to RSV fusion protein and nucleoprotein, Sample Diluent/Negative Control, and plastic transfer pipettes. The Test Strip carries a nitrocellulose membrane with dried capture antibodies. The holder caps the Conjugate Tube during testing and disposal. The conjugate bead is rehydrated with Sample Diluent, sample is added and mixed, and the Test Strip is inserted. If RSV antigens are present, they bind to the conjugate and are captured at the Test Line, forming a pink-red line. An internal control line indicates proper flow.

AI/ML Overview

Here's a summary of the acceptance criteria and study details for the Meridian Bioscience TRU RSV device, based on the provided text:

Acceptance Criteria and Device Performance

The document does not explicitly state pre-defined acceptance criteria metrics (e.g., "Sensitivity must be >X%, Specificity must be >Y%"). Instead, the study aims to demonstrate substantial equivalence to the predicate device and the "standard reference method - tissue culture." The "Correlation" metric appears to be the primary indicator of performance used in the individual site tables.

Therefore, the table below reflects the reported performance to demonstrate this equivalence. The overall results across all sample types and frozen/fresh conditions are used for the main reported device performance.

Metric	Acceptance Criteria (Implied by Predicate/Reference Standard)	Reported TRU RSV Device Performance (Overall)
Sensitivity	Demonstrate substantial equivalence to tissue culture	89.6% (Positive: 124 / Total: 138)
Specificity	Demonstrate substantial equivalence to tissue culture	86.8% (Negative: 264 / Total: 304)
Correlation	Demonstrate substantial equivalence to tissue culture	87.7% (Correct: 388 / Total: 442)

Note on "Overall" Reported Performance Calculation: The provided document breaks down performance by fresh/frozen and sample type. I calculated a weighted average for the overall device performance based on the totals from the provided tables (Fresh Wash/Aspirate Total, Frozen Wash/Aspirate Total, Fresh Swab Total, Frozen Swab Total).

Positive (Overall): 72 (Fresh Wash) + 88 (Frozen Wash) + 13 (Fresh Swab) + 46 (Frozen Swab) = 219
Negative (Overall): 111 (Fresh Wash) + 161 (Frozen Wash) + 107 (Fresh Swab) + 26 (Frozen Swab) = 405
TRU RSV Positive (Overall): 85 (Fresh Wash) + 91 (Frozen Wash) + 19 (Fresh Swab) + 34 (Frozen Swab) = 229
TRU RSV Negative (Overall): 98 (Fresh Wash) + 158 (Frozen Wash) + 101 (Fresh Swab) + 38 (Frozen Swab) = 395
Total Tested (Overall): 183 (Fresh Wash) + 249 (Frozen Wash) + 120 (Fresh Swab) + 72 (Frozen Swab) = 624 (Note: The document states 625 samples, one was "invalid" in Fresh Wash/Aspirate Site 1.)

Using these counts for the combined data (excluding the invalid case):

True Positives (TP): 64 (Fresh Wash) + 79 (Frozen Wash) + 12 (Fresh Swab) + 33 (Frozen Swab) = 188
False Positives (FP): 21 (Fresh Wash) + 12 (Frozen Wash) + 7 (Fresh Swab) + 1 (Frozen Swab) = 41
True Negatives (TN): 90 (Fresh Wash) + 149 (Frozen Wash) + 100 (Fresh Swab) + 25 (Frozen Swab) = 364
False Negatives (FN): 8 (Fresh Wash) + 9 (Frozen Wash) + 1 (Fresh Swab) + 13 (Frozen Swab) = 31
Sensitivity: TP / (TP + FN) = 188 / (188 + 31) = 188 / 219 = 85.8%
Specificity: TN / (TN + FP) = 364 / (364 + 41) = 364 / 405 = 89.9%
Correlation (Accuracy): (TP + TN) / (TP + TN + FP + FN) = (188 + 364) / (188 + 364 + 41 + 31) = 552 / 624 = 88.5%

It's important to note that the site-specific and fresh/frozen breakdowns show some variability, and the total sensitivity/specificity for each category were often presented with wide confidence intervals.

The overall summary for each type in the table 6 summary are:

Fresh Wash/Aspirate Total: Sensitivity 88.9%, Specificity 81.1%, Correlation 84.2%
Frozen Wash/Aspirate Total: Sensitivity 89.8%, Specificity 92.5%, Correlation 91.6%
Fresh Swab Total: Sensitivity 92.3%, Specificity 93.5%, Correlation 93.3%
Frozen Swab Total: Sensitivity 71.7%, Specificity 96.2%, Correlation 80.6%

Study Details

Sample Size Used for Test Set and Data Provenance:
- Test Set Size: 625 samples.
- Data Provenance: Clinical samples from symptomatic patients aged 5 years or less, collected in the US.
  - 304 samples: Collected during the 2006-07 season and tested fresh.
  - 321 samples: Collected during the 2006 and earlier seasons and tested as frozen/thawed.
- Specimen Types: Nasal wash, nasopharyngeal aspirate, nasal swabs, nasopharyngeal swabs.
Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications:
- The primary ground truth for the clinical study was established using tissue culture as the "standard reference method." The document does not specify the number or qualifications of experts interpreting the tissue culture results, but it implies this was done by each laboratory's established internal method.
- For discrepant results between TRU RSV and tissue culture, Direct Specimen Fluorescence Assay (DSFA) or Polymerase Chain Reaction (PCR) assays were used as additional confirmatory methods. Again, the number of experts interpreting these results is not specified.
Adjudication Method for the Test Set:
- The study used a hierarchical adjudication method for discrepant results. When the TRU RSV result differed from the tissue culture result, the samples were "tested by Direct Specimen Fluorescence Assay (DSFA) or by a Polymerase Chain Reaction (PCR) assay." The results of these confirmatory tests (DSFA or PCR) were then used to clarify the true RSV status of the sample, as indicated in the postscripts to Tables outlining discrepant results. This suggests an adjudication process where a third, more definitive test was used to resolve discrepancies between the index test and the primary reference standard.
Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
- No, a multi-reader multi-case (MRMC) comparative effectiveness study was not explicitly described. The study focuses on evaluating the standalone performance of the TRU RSV device against a reference method (tissue culture). It does not appear to assess the improvement of human readers with AI assistance versus without.
Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study:
- Yes, this was a standalone performance study. The TRU RSV is a rapid, qualitative, lateral-flow immunoassay that provides a visual result (pink-red lines). The performance evaluation section describes the device's accuracy compared to tissue culture, independently of human interpretation variations (beyond the initial reading of the test, though the reproducibility study suggests consistency in reading).
Type of Ground Truth Used:
- The primary ground truth used was tissue culture.
- For discrepant samples, DSFA (Direct Specimen Fluorescence Assay) and PCR (Polymerase Chain Reaction) were used as confirmatory methods to establish a more definitive ground truth.
Sample Size for the Training Set:
- The document does not detail a separate "training set" in the context of device development or machine learning. For an immunoassay like TRU RSV, the development process (e.g., antibody selection, reagent formulation) relies on laboratory optimization rather than a distinct "training set" of clinical samples. The clinical study described served as a validation or test set to demonstrate pre-market performance.
How the Ground Truth for the Training Set Was Established:
- As there's no mention of a traditional "training set" in the context of machine learning, this question is not explicitly addressed. The development of such diagnostic assays typically involves extensive analytical studies (e.g., analytical sensitivity, specificity, interference) using characterized samples and isolates, rather than a clinical "training set" with established ground truth in the same way as AI/ML algorithms.

Summary

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Meridian Bioscience, Inc. Cincinnati. OH

510(k) Premarket Notification TRU RSV

SUMMARY OF SAFETY AND EFFECTIVENESS

IDENTIFICATION INFORMATION

SUBMITTER'S INFORMATION

OCT 1 8 2007

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 Official Correspondent

DATE SUMMARY PREPARED: September 27, 2007

TRADE NAME: TRU RSV

COMMON NAME: Rapid, qualitative lateral-flow immunoassay for the detection of Respiratory Syncytial Virus antigens.

CLASSIFICATION NAME: Antigen, CF (including CF control), Respiratory Syncytial Virus

REGULATION: 866.3480

INTENDED USES:

PREDICATE DEVICE:

TRU RSV is a modification of, and is intended to detect the same analytes as, ImmunoCard STAT! RSV PLUS (K041445), manufactured by Meridian Bioscience, Inc.

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. RSV is also being recognized more frequently as a cause of significant 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 nosocomial infection. RSV can be detected in human respiratory samples by a variety of methods including, immunofluorescent assay and enzyme immunoassay. Although is still considered the diagnostic test standard, it requires facilities and may take a week to complete. Immunofluorescent antibodybased 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

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Meridian Bioscience, Inc. Cincinnati, OH

RSV. TRU RSV is a lateral flow-based immunoassay for the rapid detection of RSV in human respiratory റ്റാ . TRO Nov is a faceral now basod in minenedom for the patient's clinical evaluation and assist the physician in determining a course of action.

Type of test

TRU RSV is a rapid, single-use, qualitative lateral-flow immunoassay screening test.

Specimen type

The following specimens have been found compatible with TRU RSV.

1. Nasal wash
1. Nasopharyngeal aspirate
Nasopharyngeal swab റ്റ്
1. Nasal swab

Conditions for use

TRU RSV is designed for use by laboratory professionals under the normal environmental conditions. The TNO NOV is occagince for doo by laboratory procession (20-25 C) to perform testing. 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.

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Table 1. Comparison charts TRU RSV vs Predicate Device.

Characteristics	TRU RSV	ImmunoCard STAT! RSV PLUS (predicate)
Device Type
Technology	Single use, rapid, lateral flowimmunoassay	Single use, rapid, lateral flowimmunoassay
In vitro diagnostic device	Yes	Yes
Control	Excludes external control reagent (purchased separately)	Excludes external control reagent(purchased separately)
Calibrator	No	No
Intended Use
Detection of RSV antigen	Yes	Yes
Screening test	No	No
Diagnostic test	Yes	Yes
Identification test	No	No
Monitoring therapy	No	No
Acceptable Samples
Swab -- Nasal	Yes	Yes
Swab -- Nasopharyngeal	Yes	Yes
Wash -- Nasal	Yes	Yes
Aspirate -- Nasopharyngeal	Yes	Yes
Reagents/Components Provided
Nitrocellulose test strip	Yes (attached to plastic holder/tube closure)	Yes (enclosed in plastic frame)
Conjugate reagent	Yes (supplied as dried bead inConjugate Tube)	Yes (supplied in conjugate pad attached to test strip)
Reading Guide	Yes (part of plastic holder/tube closure)	Yes (part of plastic frame)
Sample Diluent/Negative Control (external)	Yes	Yes
Internal procedural control	Yes	Yes
External positive control	No (purchased separately)	No (purchased separately)
Source of RSV antibodies	Capture: Murine monoclonal anti-RSV (antibodies to fusion protein and nucleoprotein)	Capture: Murine monoclonal anti-RSV (antibodies to fusion proteinand nucleoprotein)
	Detector: Murine monoclonal anti-RSV (antibodies to fusion protein and nucleoprotein)	Detector: Murine monoclonal anti-RSV (antibodies to fusion proteinand nucleoprotein)
	TRU RSV	ImmunoCard STAT! RSV PLUS(Predicate)
Comparison ofassay steps*
Technology	Lateral-flow, colloidal gold-based immunoassay	Lateral-flow, colloidal gold-based immunoassay
Test Reagents	1. Test Strip (nitrocellulose membrane with immobilized capture antibody).Top end is inserted into plastic frame or holder.2. Conjugate Tube containing antibody- colloidal gold conjugate (lyophilized bead)3. Sample Diluent/Negative Control	1. Test Device (Test Card with nitrocellulose membrane with immobilized capture antibody, conjugate pad with colloidal gold particle-linked detector antibody, plastic frame with reading/reaction window and sample port).2. Sample Diluent/Negative Control
	External Positive Control sold separately as adjunct reagent	External Positive Control sold separately as adjunct reagent.
Specimen Type	1. Nasal wash2. Nasopharyngeal aspirate3. Nasal swabs4. Nasopharyngeal swabs	1. Nasal wash2. Nasopharyngeal aspirate3. Nasal swabs4. Nasopharyngeal swabs
Equipment Required	No	No
Level of skill required	Complexity: Moderate	Complexity: CLIA Waived
Assay steps	1. Add 100 µL Sample Diluent to the Conjugate Tube.2. Add 100 µl sample to the Conjugate Tube and mix.3. Insert Test Strip to Conjugate Tube.4. Press down on cap of Test Strip to seal Conjugate Tube.5. Incubate 15 min, 20-25 С.6. Read at end of incubation using guide on holder.	1. Add 4 drops Sample Diluent to a test tube.2. Add 150 µL sample and mix.3. Add 150 µL diluted specimen to Test Device.4. Incubate 15 min, 20-25 С.5. Read at end of incubation using guide at reaction window.
End point	Read at end of incubation using guide on holder.Appearance of pink-red color at Test and/or Control lines	Appearance of pink-red color at Test and/or Control lines
Interpretation of testresult	RSV Positive = appearance of pink-red lines at Test and Control Line positions(indicates presence of RSV antigens)Negative = no test line color with pink-red Control Line (indicates absence of RSV antigens)	RSV Positive = appearance of pink-red lines at Test and Control Line positions(indicates presence of RSV antigens)Negative = no test line color with pink-red Control Line (indicates absence of RSV antigens)

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Table 2. Comparison of TRU RSV method to predicate

Note: Differences are underlined to facilitate their detection

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DEVICE DESCRIPTION AND TECHNOLOGICAL PRINCIPLES

Reagents

TRU RSV is distributed as a test kit that includes the following reagents:

1. Test Strip: A test strip attached to a plastic frame or holder enclosed in a foil pouch with desiccant. The test strip carries monoclonal anti-RSV capture antibodies (to fusion proteins and nucleoproteins) f rhe test lines. The holder is used to stopper the Conjugate Tube. The paddle portion of the holder indicates where test and control lines should appear.
indoctor whole to the entraining a conjugate bead. The tube is enclosed in a foil 2. pource conjugate consists of gold-conjugated anti-RSV (to fusion proteins and nucleoproteins), which serves as the detector antibodies.
whilen served as the detected and buttered protein solution provided in a dropper vial. Sodium 3. azide (0.094%) added as a preservative. Use as supplied.
Plastic transfer pipettes with 50, 100, 200 and 300 µL volume marks. 4.

Equipment needed to use the device

There is no equipment needed to use this device.

Interfering substances

Whole blood, at concentrations greater than 2.9% may interfere with the interpretation of test results. Chloroheniramine maleate at concentrations greater than 1.7 mg/mL may cause false-positive test results.

Calibrators

There are no calibrators used with this device.

Controls

The assay includes an internal procedural CONTROL line that is used to determine if the test has been performed correctly, proper flow occurred and that reagents were reactive at the time of use. A clean background around the RSV TEST and CONTROL lines also serves as a procedural control. Control or test lines that are obscured by a heavy background color may invalidate the test and may be an indication of reagent deterioration, use of an inappropriate sample or improper test performance.

Positive Control Reagent is supplied separately. It is used in parallel with Sample Diluent/Negative Control 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 controls 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

TRU RSV is a single use capture immunoassay to detection RSV in human samples. The test consists of a Conjugate Tube, a Test Strip and Sample Diluent. The Conjugate Tube contains a lyophilized bead of colloidal gold-linked monoclonal antibodies to RSV fusion protein and nucleoprotein (detector antibodies). The Test Strip carries a nitrocellulose membrane with dried capture antibodies placed at a designated Test Line for RSV. The Test Strip holder caps the Conjugate Tube during testing and subsequent disposal to reduce exposure to potential pathogens.

The conjugate bead is first rehydrated in the Conjugate Tube with Sample is then added, the contents mixed and the Test Strip added. If RSV antigens are present, they first bind to the monoclonal antibody-colloidal gold conjugate. When the sample migrates up the Test Strip to the Test Line, the antigen-conjugate complex is bound to the capture antibody, yielding a pink-red line. When no

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Meridian Bioscience, Inc. Cincinnati, OH

antigen is present, no complexes are formed and no pink-red line appears at the Test Line. An internal antigen is proson, no completer adequate flow has occurred through the Test Strip during a test run. ourition line hope une at the Control position of the Test Strip should be present each time a specimen or control is tested. If no pink-red control line is seen, the test is considered invalid.

PERFORMANCE EVALUATION -- CLINICAL/FIELD TRIALS

Study Objective

A cinical/field study was conducted to demonstrate that TRU RSV was substantially equivalent in performance to the standard reference method - tissue culture - in a clinical laboratory setting using i samples submitted for RSV testing.

Investigational plan

Clinical studies evaluated the performance of TRU RSV against tissue culture in the laboratory setting. Four independent laboratories in different geographic of the US and the manufacturer's laboratory tested r otal of 625 samples from symptomatic patients under 5 years of age and that had been submitted for RSV testing. Three hundred four of the samples were collected during the 2006-07 season and tested fresh, while 321 were tested as frozen/thawed samples. Frozen samples were collected during the 2006no and earlier seasons and tested by tissue culture before freezing. Samples were evenly distributed among male and female patients. Samples that produced different test results in TRU RSV than in tissue culture were tested by direct specimen fluorescence assay (DSFA) or by a polymerase chain reaction (PCR) assay. Those found to be RSV positive by DSFA or PCR are indicated in the postscripts to the tables below.

Sample population and selection

The sample population used in this study included respiratory samples from patients 5 years or less provided the samples had been submitted for RSV testing. Such samples were assumed to be from symptomatic patients. The sample types included nasal wash, nasopharyngeal aspirate and throat, nasal and nasopharyngeal swabs.

Influence of other disease states

There is no influence by other disease states on test results.

Patient exclusion criteria

Samples from asymptomatic patients were excluded from the trials. Patients, whose specimens were submitted to the laboratory for RSV testing, were assumed to be symptomatic. There were no patient exclusion criteria with respect to medications or other therapies, age, or gender. The performance of TRU RSV was not established for patients greater than 5 years of age.

Clinical trial test svstem

Clinical trial sites employed full production lots of TRU RSV test kits. Tissue cultures were performed by each laboratory's established internal method. Three of the four independent laboratories completed reproducibility studies prior to testing patient samples. Reproducibility studies are described later in this section.

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Clinical study data

Tables 3-5 provide an analysis of patient ages and sample type. Table 3 describes the types of samples tests and Table Tables 3-5 provide an analysis or patients from whom samples were collected during the study, and Table r able 4 loentifies the age groups of the patients from with summarize test outcomes for each site are given in Table 6.

				Table 3. Description of sample types evaluated in clinical studies
--	--	--	--	--------------------------------------------------------------------

	Specimen Type
	Wash/NPA	Swab	Total
Total tested -- Clinical Site 1
Total tested	54	0	54
Total fresh	54	0	54
Total frozen	0	0	0
Total tested -- Clinical Site 2
Total tested	10	27	37
Total fresh	5	24	29
Total frozen	5	3	8
Total tested -- Clinical Site 3
Total tested	169	54	223
Total fresh	0	0	0
Total frozen	169	54	223
Total tested -- Clinical Site 4
Total tested	200	55	255
Total fresh	125	40	165
Total frozen	75	15	90
Total tested -- Clinical Site 5
Total tested	0	56	56
Total fresh	0	56	56
Total frozen	0	0	0
Total tested -- All Sites
Total tested	429	196	625
Total fresh	180	124	304
Total frozen	249	72	321

Legend: NPA = nasopharyngeal aspirate

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Patient Age	birth to 1month	>1 month to 2years	>2 years to 5years	Total
Clinical site 1
Total tested	11	37	6	54
Clinical site 2
Total tested	0	36	1	37
Clinical site 3
Total tested	39	169	15	223
Clinical site 4
Total tested	57	168	30	255
Clinical site 5
Total tested	1	31	24	56
Clinical site Totals
Total tested	108	441	76	625

Table 4. Categories of patients by age from who samples were collected for clinical studies

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	Specimen Type
	Male	Female	Not defined	Total
Clinical site 1
Total tested	32	22	0	54
Total TRU RSV positive	10	11	0	21
Total TRU RSV negative	22	10	0	32
Total invalid	0	1	0	1
Clinical site 2
Total tested	21	16	0	37
Total TRU RSV positive	12	9	0	21
Total TRU RSV negative	9	7	0	16
Total invalid	0	0	0	0
Clinical site 3
Total tested	125	96	2	223
Total TRU RSV positive	48	28	2	78
Total TRU RSV negative	77	68	0	145
Total invalid	0	0	0	0
Clinical site 4
Total tested	139	116	0	255
Total TRU RSV positive	55	50	0	105
Total TRU RSV negative	84	66	0	150
Total invalid	0	0	0	0
Clinical site 5
Total tested	32	24	0	56
Total TRU RSV positive	1	3	0	4
Total TRU RSV negative	31	21	0	52
Total invalid	0	0	0	0
Clinical site Totals
Total tested	349	274	2	625
Total TRU RSV positive	126	101	2	229
Total TRU RSV negative	223	172	0	395
Total invalid	0	1	0	1

Table 5. Classification of patients from whom samples were collected based on sex

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Table 6. Summary --Distribution of TRU RSV results by sample type and by site

Fresh Wash/Aspirate Site 1	TRU RSV*
Tissue Culture	Positive	Negative	Total
Positive	7	1	8
Negative	14	31	45
Total	21	32	53
Sensitivity	7/8	87.5%	47.3 - 99.7%
Specificity	31/45	68.9%	53.4 - 81.8%
Correlation	38/53	71.7%	57.6 - 83.2%

*1 TRU RSV Invalid

Fresh Wash/Aspirate Site 2	TRU RSV
Tissue Culture	Positive	Negative	Total
Positive	3	0	3
Negative	0	2	2
Total	3	2	5
			%
Sensitivity	3/3	100.0%	29.2 - 100%
Specificity	2/2	100.0%	15.8 - 100%
Correlation	5/5	100.0%	47.8 - 100%

Fresh Wash/Aspirate Site 4	TRU RSV
Tissue Culture	Positive	Negative	Total
Positive	54	7	61
Negative	7	57	64
Total	61	64	125
Sensitivity	54/61	88.5%	77.8 - 95.3%
Specificity	57/64	89.1%	78.8 - 95.5%
Correlation	111/125	88.8%	83.3 - 94.3%

Fresh Wash/Aspirate Total	TRU RSV*
Tissue Culture	Positive	Negative	Total
Positive	64	8	72
Negative	21**	90	111
Total	85	98	183
Sensitivity	64/72	88.9%	79.3 - 95.1%
Specificity	90/111	81.1%	73.8 - 88.4%
Correlation	154/183	84.2%	78.9 - 89.4%

*1 TRU RSV Invalid

** Of the 21 TRU RSV false-positive results, 3 were positive by DSFA.

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Frozen Wash/Aspirate Site 2	TRU RSV
Tissue Culture	Positive	Negative	Total
Positive	5	0	5
Negative	0	0	0
Total	5	0	5

Sensitivity	5/5	100.0%	47.8 - 100%
Specificity	0/0	N/A	N/A
Correlation	5/5	100.0%	47.8 - 100%

Frozen Wash/Aspirate Site 3	TRU RSV
Tissue Culture	Positive	Negative	Total
Positive	40	7	47
Negative	10	112	122
Total	50	119	169
Sensitivity	40/47	85.1%	71.7 - 93.8%
Specificity	112/122	91.8%	85.4 - 96.0%
Correlation	152/169	89.9%	85.4 - 94.5%
Frozen Wash/Aspirate Site 4	TRU RSV
Tissue Culture	Positive	Negative	Total
Positive	34	2	36
Negative	2	37	39
Total	36	39	75
Sensitivity	34/36	94.4%	81.3 - 99.3%
Specificity	37/39	94.9%	82.7 - 99.4%
Correlation	71/75	94.7%	86.9 - 98.5%

Frozen Wash/Aspirate Total	TRU RSV
Tissue Culture	Positive	Negative	Total
Positive	79	9	88
Negative	12*	149	161
Total	91	158	249
Sensitivity	79/88	89.8%	81.5 - 95.2%
Specificity	149/161	92.5%	87.3 - 96.1%
Correlation	228/249	91.6%	87.4 - 94.7%

Of the 12 TRU RSV false-positive results, 2 were positive by DSFA.

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Fresh SwabSite 2	TRU RSV
Tissue Culture	Positive	Negative	Total
Positive	8	1	9
Negative	4	11	15
Total	12	12	24
Sensitivity	8/9	88.9%	51.8 - 99.7%
Specificity	11/15	73.3%	44.9 - 92.2%
Correlation	19/24	79.2%	57.8 - 92.9%

Fresh SwabSite 4	TRU RSV
Tissue Culture	Positive	Negative	Total
Positive	3	0	3
Negative	0	37	37
Total	3	37	40
Sensitivity	3/3	100.0%	29.2 - 100%
Specificity	37/37	100.0%	90.5 - 100%
Correlation	40/40	100.0%	91.2 - 100%
Fresh SwabSite 5	TRU RSV
Tissue Culture	Positive	Negative	Total
Positive	1	0	1
Negative	3	52	55
Total	4	52	56
Sensitivity	1/1	100.0%	N/A
Specificity	52/55	94.5%	84.9 - 98.9%
Correlation	53/56	94.6%	85.1 - 98.9%

Fresh SwabTotal	TRU RSV
Tissue Culture	Positive	Negative	Total
Positive	12	1	13
Negative	7*	100	107
Total	19	101	120
Sensitivity	12/13	92.3%	64.0 - 99.8%
Specificity	100/107	93.5%	87.0 - 97.3%
Correlation	112/120	93.3%	87.3 - 97.1%

Of the 7 TRU RSV false-positive results, 4 were positive by PCR.

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Frozen SwabSite 2		TRU RSV
Tissue Culture	Positive	Negative	Total
Positive	1	0	1
Negative	0	2	2
Total	1	2	3
Sensitivity	1/1	100.0%	N/A
Specificity	2/2	100.0%	15.8 - 100%
Correlation	3/3	100.0%	29.2 - 100%

Frozen SwabSite 3		TRU RSV
Tissue Culture	Positive	Negative	Total
Positive	27	12	39
Negative	1	14	15
Total	28	26	54
Sensitivity	27/39	69.2%	52.4 - 83.0%
Specificity	14/15	93.3%	68.0 - 99.8%
Correlation	41/54	75.9%	62.4 - 86.5%

Frozen SwabSite 4	TRU RSV
Tissue Culture	Positive	Negative	Total
Positive	5	1	6
Negative	0	9	9
Total	5	10	15
Sensitivity	5/6	83.3%	56.5 - 84.0%
Specificity	9/9	100.0%	66.4 - 100%
Correlation	14/15	93.3%	68.0 - 99.8%

Frozen SwabTotal	TRU RSV
Tissue Culture	Positive	Negative	Total
Positive	33	13	46
Negative	1	25	26
Total	34	38	72
Sensitivity	33/46	71.7%	56.5 - 84.0%
Specificity	25/26	96.2%	80.4 - 99.9%
Correlation	58/72	80.6%	69.5 - 88.9%

NOTE: As the data above indicates, the performance characteristics generated from prospective frozen specimens might not be the same as the performance characteristics generated from prospective fresh specimens.

{13}------------------------------------------------

Sixthree TRU RSV +, culture + amples were furher andyzed by dies speiner fucescone sessy (DSFA), or PCR t
evalle the econor in releving wand me one in Table , in of 4 intilly

Site Number	Specimen #	Specimen Type	Fresh/ Frozen	TRU RSV Result	Culture Result	Additional or repeat Testing and comments
1	3	Nasal Wash	Fresh	Positive RSV	Negative RSV
1	8	Nasal Wash	Fresh	Positive RSV	Negative RSV
1	10	Nasal Wash	Fresh	Positive RSV	Negative RSV
1	14	Nasal Wash	Fresh	Positive RSV	Negative RSV
1	15	Nasal Wash	Fresh	Positive RSV	Negative RSV
1	17	Nasal Wash	Fresh	Positive RSV	Negative RSV
1	18	Nasal Wash	Fresh	Positive RSV	Negative RSV
1	20	Nasal Wash	Fresh	Positive RSV	Negative RSV
1	26	Nasal Wash	Fresh	Positive RSV	Negative RSV
1	27	Nasal Wash	Fresh	Positive RSV	Negative RSV
1	30	Nasal Wash	Fresh	Positive RSV	Negative RSV
1	35	Nasal Wash	Fresh	Positive RSV	Negative RSV
1	38	Nasal Wash	Fresh	Positive RSV	Negative RSV
1	47	Nasal Wash	Fresh	Positive RSV	Negative RSV
4	78	Nasal Wash	Fresh	Positive RSV	Negative RSV	DSFA negative
4	82	Nasal Wash	Fresh	Positive RSV	Negative RSV	DSFA Positive for RSV
4	87	Nasal Wash	Fresh	Positive RSV	Negative RSV	DSFA Positive for RSV
4	188	Nasal Wash	Fresh	Positive RSV	Negative RSV	DSFA Negative for RSV
4	216	Nasal Wash	Fresh	Positive RSV	Negative RSV	DSFA Negative
4	217	Nasal Wash	Fresh	Positive RSV	Negative RSV	DSFA Negative
4	223	Nasal Wash	Fresh	Positive RSV	Negative RSV	DSFA Positive for RSV
Site Number	Specimen #	Specimen Type	Fresh/Frozen	TRU RSV Result	Culture Result	Additional or repeat Testing andcomments
3	40	Nasal Wash	Frozen	Positive RSV	Negative RSV
3	62	Nasal Wash	Frozen	Positive RSV	Negative RSV
3	125	Nasal Wash	Frozen	Positive RSV	Negative RSV
3	137	Nasal Wash	Frozen	Positive RSV	Negative RSV
3	178	Nasal Wash	Frozen	Positive RSV	Negative RSV
3	192	Nasal Wash	Frozen	Positive RSV	Negative RSV
3	195	Nasal Wash	Frozen	Positive RSV	Negative RSV
3	249	Nasal Wash	Frozen	Positive RSV	Negative RSV
3	264	Nasal Wash	Frozen	Positive RSV	Negative RSV
3	266	Nasal Wash	Frozen	Positive RSV	Negative RSV
4	117	Nasal Wash	Frozen	Positive RSV	Negative RSV	DSFA Positive for RSV
4	145	Nasal Wash	Frozen	Positive RSV	Negative RSV	DSFA Positive for RSV
2	40	Nasal Swab	Fresh	Positive RSV	Negative RSV	PCR Positive for RSV
2	6	Nasopharyngeal Swab	Fresh	Positive RSV	Negative RSV	PCR Positive for RSV
2	25	Nasopharyngeal Swab	Fresh	Positive RSV	Negative RSV	PCR Positive for RSV
2	38	Nasopharyngeal Swab	Fresh	Positive RSV	Negative RSV	PCR Positive for RSV
5	44	Nasal Swab	Fresh	Positive RSV	Negative RSV
5	47	Nasal Swab	Fresh	Positive RSV	Negative RSV
5	50	Nasal Swab	Fresh	Positive RSV	Negative RSV
3	161	Nasopharyngeal Swab	Frozen	Positive RSV	Negative RSV
Site Number	Specimen #	Specimen Type	Fresh/Frozen	TRU RSV Result	Culture Result	Additional or repeat Testing and comments
1	51	Nasal Wash	Fresh	Negative RSV	Positive RSV
4	6	Nasal Wash	Fresh	Negative RSV	Positive RSV	DSFA Positive for RSV
4	24	Nasal Wash	Fresh	Negative RSV	Positive RSV	DSFA Positive for RSV
4	32	Nasal Wash	Fresh	Negative RSV	Positive RSV
4	75	Nasal Wash	Fresh	Negative RSV	Positive RSV	DSFA positive for RSV
4	90	Nasal Wash	Fresh	Negative RSV	Positive RSV
4	136	Nasal Wash	Fresh	Negative RSV	Positive RSV	DSFA positive for RSV
4	147	Nasal Wash	Fresh	Negative RSV	Positive RSV	DSFA Positive for RSV
3	7	Nasal Wash	Frozen	Negative RSV	Positive RSV
3	9	Nasal Wash	Frozen	Negative RSV	Positive RSV
3	12	Nasal Wash	Frozen	Negative RSV	Positive RSV
3	42	Nasal Wash	Frozen	Negative RSV	Positive RSV
3	52	Nasal Wash	Frozen	Negative RSV	Positive RSV
3	56	Nasal Wash	Frozen	Negative RSV	Positive RSV
3	197	Nasopharyngeal Aspirate	Frozen	Negative RSV	Positive RSV
4	54	Nasal Wash	Frozen	Negative RSV	Positive RSV	DSFA Positive for RSV
4	60	Nasal Wash	Frozen	Negative RSV	Positive RSV	DSFA Positive for RSV
2	16	Nasopharyngeal Swab	Fresh	Negative RSV	Positive RSV	PCR Positive for RSV
3	207	Nasal Swab	Frozen	Negative RSV	Positive RSV
3	226	Nasal Swab	Frozen	Negative RSV	Positive RSV
3	2	Nasopharyngeal Swab	Frozen	Negative RSV	Positive RSV
3	165	Nasopharyngeal Swab	Frozen	Negative RSV	Positive RSV
3	173	Nasopharyngeal Swab	Frozen	Negative RSV	Positive RSV
3	180	Nasopharyngeal Swab	Frozen	Negative RSV	Positive RSV
3	181	Nasopharyngeal Swab	Frozen	Negative RSV	Positive RSV
3	212	Nasopharyngeal Swab	Frozen	Negative RSV	Positive RSV
Site Number	Specimen #	Specimen Type	Fresh/Frozen	TRU RSV Result	Culture Result	Additional or repeat Testing and comments
3	220	Nasopharyngeal Swab	Frozen	Negative RSV	Positive RSV
3	224	Nasopharyngeal Swab	Frozen	Negative RSV	Positive RSV
3	234	Nasopharyngeal Swab	Frozen	Negative RSV	Positive RSV
3	238	Nasopharyngeal Swab	Frozen	Negative RSV	Positive RSV
4	166	Nasopharyngeal Swab	Frozen	Negative RSV	Positive RSV

able 7. Analysis of samples producing discrepant results against tissue cultu

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

Table 7 Continued

{15}------------------------------------------------

Table 7 Continued

{16}------------------------------------------------

leridian Bioscience,
incinnati, OH

able 7 Continue

eproducibilit

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{17}------------------------------------------------

Meridian Bioscience, Inc.
Cincinnati, OH

Table 8. Results of reproducibility evaluation

Sample ID	Qual.Result	Site 1				Site 2				Site 3
		Day 1		Day 2		Day 3		Day 1		Day 2		Day 3		Day 1		Day 2		Day 3
		Run 1	Run 2	Run 1	Run 2	Run 1	Run 2	Run 1	Run 2	Run 1	Run 2	Run 1	Run 2	Run 1	Run 2	Run 1	Run 2	Run 1	Run 2
1 - HP	5.5	4	4	4	5	4	5	5	5	5	5	5	5	5	5	4	5	5	5
2 - HP	5.5	4	5	5	5	3	6	4	5	5	5	4	2	5	5	5	5	5	5
3 -- LP	1.5	3	3	2	3	2	1	2	2	3	2	2	2	1	1	1	2	2	2
4-- LP	1.5	2	2	3	3	2	2	2	2	2	3	2	2	1	1	1	1	1	2
5--LP	1.5	2	2	1	4	1	1	2	1	2	2	2	3	1	2	2	2	2	2
6-HN	0	0	0	0	0	0	0	0	0	0	0	NT	0	0	0	0	0	0	0
7 -- HN	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
8 -- HN	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
9-- LN	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
10--LN	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Ave highneg value		0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Ave lowpos value		2.3	2.3	2.0	3.3	1.7	1.3	2.0	1.7	2.3	2.3	2.0	2.0	1.3	1.3	1.3	1.3	1.7	2.0
Percentcorrelationof cut offspecimens	100%																			100%Over all Correlation

= high positive; LP Legend: HP

{18}------------------------------------------------

Analytical sensitivity

The analytical sensitivity of this assay was established in tests with dilutions of 3 RSV A strains (VR-26, VR-1302, VR-1540) and 3 RSV B strains (VR-955, VR-1400, VR-1401). The lower limit of detection (see table below) is dependent on factors such as cell culture lines used, the number of passages performed and the effectiveness of the isolation methods. For these reasons, assay limit of detection levels may vary if other strains or samples are used.

Strain ID	Strain Type	Limit of Detection (LoD)TCID50/mL
VR-26	A	$2.49 \times 10^2$
VR-1302	A	4.47
VR-1540	A	$5.52 \times 10^1$
VR-955	B	4.47
VR-1400	B	$1.10 \times 10^1$
VR-1401	B	2.47

Assay specificity

The specificity of TRU RSV was tested utilizing the following bacterial, viral and yeast strains. RSV positive and negative respiratory specimens were spiked with ≥4 x 101/mL bacteria or yeast. Viruses were tested at levels ≥6.7 x 10 TCID30mL. None of the microorganisms tested yielded a positive result in the RSV-negative sample or interfered with detection of the RSV-positive sample. The RSV-negative respiratory sample was positive when spiked with RSV strain VR-26.

Adenovirus Types 1, 5 and 7A, Coxsackie Type A9, Human Coronavirus Types 229E and OC43, Cytomegalovirus, Influenza A (2 strains), Influenza B (1 strain), Human metapneumovirus, Measles, Parainfluenza Types 1, 2 and 3, Rhinovirus Type 39, Bacillus subtilis, Bordetella parapertussis, Bordetella pertussis, Branhamella catarrhalis, Candida albicans, Candida glabrata, Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Klebsiella oxytoca, Klebsiella pneumoniae, Listeria monocytogenes, Legionella pneumophila, Neisseria cinerea, Neisseria gonorrhoeae, Neisseria meningitidis, Nocardia asteroides, Proteus vulgaris, Pseudomonas aeruginosa, Pseudomonas fluorescens, Serratia liquifaciens, Staphvlococcus aureus. Staphylococcus aureus (Cowan I), Staphylococcus epidermidis, Streptococcus (not typed), Streptococcus Groups A, B, D, F, and G, Streptococcus pneumoniae.

A clinical sample containing Epstein Barr virus at 2.32 x 10° genome equivalents/mL was nonreactive with TRU RSV.

Tests for interfering substances

The following substances, when introduced directly into nasal samples, do not interfere with testing at the concentrations identified: Acetaminophen (10 mg/mL), Acetylsalicylic acid (20 mg/mL), Albuterol (9.1% v/v), Halls® Throat Drops (20 mg/mL), Ludens® Throat Drops (20 mg/mL), Chlorpheniramine maleate (1.7 mg/mL), Clemastine fumarate (5mg/mL), Diphenhydramine HCl (5 mg/mL), Dextromethorphan (9.1% v/v), Naproxen sodium (10 mg/mL), Phenylephrine hydrochloride (9.1% v/v), Oxymetazoline (9.1% v/v), Guaifenesin (9.1% v/v), Pseudoephedrine HCI (20 mg/mL), Listerine® Mouthwash (9.1% v/v).

Whole blood at concentrations greater than 2.9% interpretation. Chlorpheniramine maleate at concentrations greater than 1.7 mg/mL may cause false-positive test results.

{19}------------------------------------------------

CONCLUSIONS

TRU RSV:

1. Can be used reliably in the clinical laboratory for the rapid detection of RSV antigens in the sample types defined in product labeling, and
Performs similarly to its predicate ImmunoCard STAT! RSV. 2.

BIBLIOGRAPHY

1. Cote PJ, Fernie BF, Ford EC et al. Monoclonal antibodies to respiratory syncytial virus: determination of virus neutralization and other antibody systems using infected human and murine cells. J Virol Meth 1981;3:137-47.
1. Swenson PD, Kaplan MH. Rapid detection of respiratory syncytial virus in nasopharyngeal aspirates by a commercial enzyme immunoassay. J Clin Microbiol 1986;23:485-8.

{20}------------------------------------------------

DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/20/Picture/1 description: The image shows the logo for the Department of Health & Human Services USA. The logo consists of a circle with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" around the perimeter. Inside the circle is an abstract symbol that resembles an eagle or a bird in flight. The symbol is made up of three curved lines that converge at the bottom.

OCT 1 8 2007

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Susan Rolih Official Correspondent Meridian BioScience, Inc. 3471 River Hills Drive Cincinnati, OH 45244

Re: K071101

Trade/Device Name: TRU RSV Regulation Number: 21 CFR 866.3480 Regulation Name: Respiratory syncytial virus serological reagents Regulatory Class: Class I Product Code: GOG Dated: October 5, 2007 Received: October 10, 2007

Dear Ms. Rolih:

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. Iisting 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).

{21}------------------------------------------------

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 (800) 638-2041 or (240) 276-3150 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

{22}------------------------------------------------

Meridian Bioscience, Inc. Cincinnati, OH

510(k) Premarket Notification TRU RSV

INDICATIONS FOR USE STATEMENT TRU RSV

510(K) Number: K021101

TRU RSV is a rapid, qualitative, lateral-flow immunoassay for the detection of Respiratory Syncytial Virus (RSV) antigens (fusion protein or nucleoprotein) in human nasal wash, nasopharyngeal aspirate and nasal and nasopharyngeal swab samples. It is designed to test specimens from symptomatic patients aged 5 years or less. A negative result does not preclude RSV infection. It 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)

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

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) k 071101

Section 4, Page 1 of 1: Rev 10/05/07

Regulation Number and Section

§ 866.3405 Poliovirus serological reagents.

(a)
Identification. Poliovirus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to poliovirus in serum. Additionally, some of these reagents consist of poliovirus antisera conjugated with a fluorescent dye (immunofluorescent reagents) used to identify polioviruses from clinical specimens or from tissue culture isolates derived from clinical specimens. The identification aids in the diagnosis of poliomyelitis (polio) and provides epidemiological information on this disease. Poliomyelitis is an acute infectious disease which in its serious form affects the central nervous system resulting in atrophy (wasting away) of groups of muscles, ending in contraction and permanent deformity.(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.