IMMUNOCARD STAT! FLU A & B

K041626 · Meridian Bioscience, Inc. · PSZ · Mar 16, 2005 · Microbiology

Device Facts

• Record ID: K041626
• Device Name: IMMUNOCARD STAT! FLU A & B
• Applicant: Meridian Bioscience, Inc.
• Product Code: PSZ · Microbiology
• Decision Date: Mar 16, 2005
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3328
• Device Class: Class 2

Intended Use

ImmunoCard STAT!® Flu A&B is a rapid, qualitative, lateral-flow immunoassay for detecting both influenza A and influenza B viral nucleoprotein antigens in human nasal wash, nasopharyngeal aspirate, and nasopharyngeal swab samples. It is designed to test samples from symptomatic patients. It is recommended that all negative test results be confirmed by cell culture.

Device Story

Lateral-flow immunoassay for rapid, qualitative detection of influenza A and B viral nucleoproteins. Input: nasal wash, nasopharyngeal aspirate, or nasopharyngeal swab samples. Principle: sample migrates through membrane containing colloidal gold-conjugated anti-influenza A and B antibodies; if antigens present, they bind to immobilized capture antibodies at test lines, forming visible pink-red lines. Control line confirms proper flow and reagent activity. Used in clinical laboratory settings by professionals. No instrumentation required. Results support clinical evaluation to assist physician in determining patient management and antiviral treatment course.

Clinical Evidence

Clinical performance evaluated using prospective (fresh) and retrospective (frozen) nasal wash, aspirate, and swab samples from symptomatic patients. Compared against cell culture (gold standard). Sensitivity and specificity metrics were calculated for both influenza A and B. Reproducibility was assessed across three clinical sites using a 14-specimen panel, showing 100% inter-assay and intra-assay reproducibility. No high-dose hook effect observed.

Technological Characteristics

Lateral-flow immunoassay; nitrocellulose membrane with immobilized monoclonal antibodies; colloidal gold-conjugated detector antibodies. Sample diluent contains 0.095% sodium azide. No instrumentation required. Storage at 2-8°C. Manual visual interpretation of test lines.

Indications for Use

Indicated for the qualitative detection of influenza A and B viral nucleoprotein antigens in nasal wash, nasopharyngeal aspirate, and nasopharyngeal swab samples from symptomatic patients. Negative results should be confirmed by cell culture.

Regulatory Classification

Identification

An influenza virus antigen detection test system is a device intended for the qualitative detection of influenza viral antigens directly from clinical specimens in patients with signs and symptoms of respiratory infection. The test aids in the diagnosis of influenza infection and provides epidemiological information on influenza. Due to the propensity of the virus to mutate, new strains emerge over time which may potentially affect the performance of these devices. Because influenza is highly contagious and may lead to an acute respiratory tract infection causing severe illness and even death, the accuracy of these devices has serious public health implications.

Special Controls

*Classification.* Class II (special controls). The special controls for this device are:(1) The device's sensitivity and specificity performance characteristics or positive percent agreement and negative percent agreement, for each specimen type claimed in the intended use of the device, must meet one of the following two minimum clinical performance criteria: (i) For devices evaluated as compared to an FDA-cleared nucleic acid based-test or other currently appropriate and FDA accepted comparator method other than correctly performed viral culture method: (A) The positive percent agreement estimate for the device when testing for influenza A and influenza B must be at the point estimate of at least 80 percent with a lower bound of the 95 percent confidence interval that is greater than or equal to 70 percent. (B) The negative percent agreement estimate for the device when testing for influenza A and influenza B must be at the point estimate of at least 95 percent with a lower bound of the 95 percent confidence interval that is greater than or equal to 90 percent. (ii) For devices evaluated as compared to correctly performed viral culture method as the comparator method: (A) The sensitivity estimate for the device when testing for influenza A must be at the point estimate of at least 90 percent with a lower bound of the 95 percent confidence interval that is greater than or equal to 80 percent. The sensitivity estimate for the device when testing for influenza B must be at the point estimate of at least 80 percent with a lower bound of the 95 percent confidence interval that is greater than or equal to 70 percent. (B) The specificity estimate for the device when testing for influenza A and influenza B must be at the point estimate of at least 95 percent with a lower bound of the 95 percent confidence interval that is greater than or equal to 90 percent. (2) When performing testing to demonstrate the device meets the requirements in paragraph (b)(1) of this section, a currently appropriate and FDA accepted comparator method must be used to establish assay performance in clinical studies. (3) Annual analytical reactivity testing of the device must be performed with contemporary influenza strains. This annual analytical reactivity testing must meet the following criteria: (i) The appropriate strains to be tested will be identified by FDA in consultation with the Centers for Disease Control and Prevention (CDC) and sourced from CDC or an FDA-designated source. If the annual strains are not available from CDC, FDA will identify an alternative source for obtaining the requisite strains. (ii) The testing must be conducted according to a standardized protocol considered and determined by FDA to be acceptable and appropriate. (iii) By July 31 of each calendar year, the results of the last 3 years of annual analytical reactivity testing must be included as part of the device's labeling. If a device has not been on the market long enough for 3 years of annual analytical reactivity testing to have been conducted since the device received marketing authorization from FDA, then the results of every annual analytical reactivity testing since the device received marketing authorization from FDA must be included. The results must be presented as part of the device's labeling in a tabular format, which includes the detailed information for each virus tested as described in the certificate of authentication, either by: (A) Placing the results directly in the device's § 809.10(b) of this chapter compliant labeling that physically accompanies the device in a separate section of the labeling where the analytical reactivity testing data can be found; or (B) In the device's label or in other labeling that physically accompanies the device, prominently providing a hyperlink to the manufacturer's public Web site where the analytical reactivity testing data can be found. The manufacturer's home page, as well as the primary part of the manufacturer's Web site that discusses the device, must provide a prominently placed hyperlink to the Web page containing this information and must allow unrestricted viewing access. (4) If one of the actions listed at section 564(b)(1)(A)-(D) of the Federal Food, Drug, and Cosmetic Act occurs with respect to an influenza viral strain, or if the Secretary of Health and Human Services (HHS) determines, under section 319(a) of the Public Health Service Act, that a disease or disorder presents a public health emergency, or that a public health emergency otherwise exists, with respect to an influenza viral strain: (i) Within 30 days from the date that FDA notifies manufacturers that characterized viral samples are available for test evaluation, the manufacturer must have testing performed on the device with those viral samples in accordance with a standardized protocol considered and determined by FDA to be acceptable and appropriate. The procedure and location of testing may depend on the nature of the emerging virus. (ii) Within 60 days from the date that FDA notifies manufacturers that characterized viral samples are available for test evaluation and continuing until 3 years from that date, the results of the influenza emergency analytical reactivity testing, including the detailed information for the virus tested as described in the certificate of authentication, must be included as part of the device's labeling in a tabular format, either by: (A) Placing the results directly in the device's § 809.10(b) of this chapter compliant labeling that physically accompanies the device in a separate section of the labeling where analytical reactivity testing data can be found, but separate from the annual analytical reactivity testing results; or (B) In a section of the device's label or in other labeling that physically accompanies the device, prominently providing a hyperlink to the manufacturer's public Web site where the analytical reactivity testing data can be found. The manufacturer's home page, as well as the primary part of the manufacturer's Web site that discusses the device, must provide a prominently placed hyperlink to the Web page containing this information and must allow unrestricted viewing access.

Predicate Devices

• Binax NOW® Flu A + B (K021649, K021646)
• BD Directigen® Flu A+B (K001364)
• Thermo-Biostar Inc. (K023556)
• QuickVue® Influenza A+ B Test (K031899)
• Xpect® Flu A/B (K031565)
• Zstatflu® Test (K982429)

Submission Summary (Full Text)

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### MAR 1 6 2005

### 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: [phone]

FAX NUMBER: [phone]

CONTACT PERSON: Susan Rolih Official Correspondent

DATE SUMMARY PREPARED: March 11, 2005

TRADE NAME: ImmunoCard STAT! Flu A & B

COMMON NAME: Rapid, qualitative lateral-flow immunoassay for the detection of Influenza A and B antigen

CLASSIFICATION NAME: Antigen, CF (including CF control), influenza virus A, B, C

REGULATION: 866.3330

#### INTENDED USES:

ImmunoCard STAT!® Flu A&B is a rapid, qualitative, lateral-flow immunoassay for detecting both influenza A and influenza B viral nucleoprotein antigens in human nasal wash, nasopharyngeal Influenza A and Innuchiza D Mar naoloop swab samples. It is designed to test samples from aspirate and nuour and has navymanded that all negative test results be confirmed by cell culture.

#### PREDICATE DEVICES:

ImmunoCard STAT! Flu A & B is intended to detect the same analytes as other cleared devices including:

- · Binax NOW® Flu A + B [a rapid lateral-flow immunoassay cleared to market under 510(k)s K021649 and K021646] (Binax, Inc. South Portland, ME)
- BD Directigen® Flu A+B [a rapid enzyme immunoassay cleared to market under 510(k) K001364) (Becton Dickinson & Co., Sparks, MD)
- · (Dector) Dicklinsdir & Oct, Open to market under 510(K) K023556] (Thermo-Biostar Inc., 1 Louisville, CO)
- Quickyue® Influenza A+ B Test [a rapid lateral-flow immunoassay cleared to market under 510(k) K031899] (Quídel, Inc., San Diego, CA)
- · Xpext® Flu A/B [a rapid immunochromatographic assay cleared to market under 510(k) K031565] (Remel, Inc., Lenexa, KS)

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- Zstatflu® Test for Influenza types A & B Virus [an endogenous viral-encoded enzyme assay cleared to market under 510(k) K982429] (ZymeTx, Inc., Oklahoma City, OK)
#### BACKGROUND:

Influenza is a highly contagious, epidemic to pandemic acute viral respiratory disease caused by into he rera for the Orthornyxoviridae family. Influenzavirus A and Influenzavirus B are the two general most commonly associated with disease in humans. (1,2) Influenza infection rates tend to be highest in pediatric populations, while serious complications from influenza disease are more common in the elderly. (2) Clinical signs and symptoms begin after a 1-4 day incubation period and include cough, fever, myalgia and malaise. The clinical presentation of influenza can range from asymptomatic infection to fatal pneumonia. (1) Influenza co-circulates with other respiratory pathogens, hence it is important to differentiate influenza from other respiratory diseases. (2) Antiviral drugs in general have shown more significant clinical benefit when administered within 48 hours of the appearance of symptoms, which obviates the need for the rapid detection of influenza. Not all antiviral drugs are effective against both influenza A and influenza B, therefore it is important to distinguish between the two. (2.4)

Influenza A and B can be detected in human respiratory samples by a variety of methods including cell culture, immunofluorescent assay and enzyme immunoassay. Cell culture isolation remains the gold standard for the detection of influenza, yet the procedure can take 7 days to complete. (1) Immunofluorescent antibody-based tests are moderately sensitive, yet highly dependent on specimen quality and preparation. The rapid detection of influenza using enzyme and microparticle-based immunoassays has become an important aspect of patient management in patients of all ages with acute respiratory disease due to influenza. (1,3,4) The results from this test are used to support data available from the patient's clinical evaluation and assist the physician in determining the course of action.

#### Type of test

ImmunoCard STAT! Flu A & B is a rapid, qualitative lateral-flow immunoassay screening test.

#### Specimen type

The following specimens have been found compatible with ImmunoCard STAT! Flu A & B

- 1. Nasal wash
- 2. Nasopharyngeal aspirate
- 3. Nasopharyngeal swab
- 4. Nasal swab

#### Conditions for use

ImmunoCard STAT! Fly A & B is designed for use by laboratory professionals under the normal environmental conditions. 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.

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### Combination with other medical devices

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

## DEVICE DESCRIPTION AND TECHNOLOGICAL PRINCIPLES

#### Reagents

lmmunoCard STAT! Flu A & B is distributed as a test kit that includes the following reagents:

ImmunoCard STAT! Flu A & B Test Device: A chromatography strip housed in a plastic ImmunoCard STAT! Fid A & B Test Bevice. "A childners application carries immobilized frame and enclosed in a for poden with a declosen... " http://www.nation.com/sident.com/wated monoconal antibody at the CONTROL ine. The strip an contains colloidal gold conjugated
anti-mouse antibody at the CONTROL line. The strip and continentials a anti-influenza anti-influenza A and anti-influenza B as the detection antibodies.

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

Positive Control: Inactivated influenza A and influenza B virus 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

Whole blood, at concentrations greater than 0.5% may interfere with the interpretation of test results.

#### 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 rne assury frolded an menter and that the conjugated detector antibody is active at the time appliou, that knowled on the background around the Flu A and Flu B 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).

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### Technological principles

ImmunoCard STAT! Flu A & B uses specific monoclonal antibodies directed at the nucleoproteins of ImmunoCard STAT! Flu A & B uses specific and detector antibodies. Motorclonal influenza A and influenza A or influenza B as the capitire and celest device at the reaction site marked
monoclonal influenza B are immobilized on the membrane of the test device at monoclonal influenza B are immobilized on the infunza B coniugated to colloidal gold
FLU A and FLU B, respectively. Monoclonal influenza B consignted to coloider one of FLU A and FLU B, respectively. Monocolial infrience A Caral Wash, nasopharyngeal
are suspended within the membrane. Toly in Cristilitad with Sample (nasely to the are suspended within the membrane. I to pendint the test, sample the same of the raded to the aspirate, nasopharyngeal swap, historial swap, be new os infor sample bind the conjugate
sample port of the Test Device. Influenza A or influenza A antigens A-cold conjug sample port of the Test Device. Thinderizates of through the shileniza A-gold conjugate
detector antibodies as the sample migrates through the society on visible a pinkdetector antibodies as the sample migrates in rough the similary and line. Similarly, a pinkcomplex will bind at the window site maked FLO A producing a winds alth e window site marked FLU
red line will appear when the influenza B-gold conjugate complex bindex fil.U red line will appear when the militenza b-gold conjugate out province.
B. In the absence of antigen, no pink-red line appears at either the FLU A or FLU B sites.

Goat antibody is bound at the membrane site marked "Control". A visible pink-red line Goat anti-mouse antibody is bound at the memblance ot in tested. Failure to obtain a should appear at this position cadin time a sample an indication of assay failure.

## DEMONSTRATION OF EQUIVALENCE TO PREDICATE DEVICES

#### The Limit of Detection (LOD)

To determine the LOD, the assay was evaluated with influenza A and influenza B antigen preparations To delemine the LOD, the assay was Crained with intessed im azide (PBSA). Table 6-1 shows (ATCC) differ the strains of influenza tested. For the purposes of this evaluation, virions/mL is the same as TCID50/mL.

| Strain ID | Strain Type | Limit of Detection (LOD) |
|-----------|-------------|--------------------------|
| VR-102 | Flu B | 533 v/mL |
| VR823 | Flu B | 630,000 v/mL |
| VR101 | Flu B | 530,000 v/mL |
| VR295 | Flu B | 187 v/mL |
| VR790 | Flu B | 15,000 v/mL |
| VR-822 | Flu A | 74,000 v/mL |
| VR97 | Flu A | 5,300 v/mL |
| VR95 | Flu A | 35,000 v/mL |
| VR547 | Flu A | 8,800 v/mL |
| VR544 | Flu A | 890 v/mL |
| VR897 | Flu A | 5,600 v/mL |

## Table 6-1. LOD determination for ImmunoCard STAT! Flu A & B.

Legend: v/mL = virions per milliliter

#### Clinical trials

Three independent laboratories and Meridian's Development Laboratory performed testing on archival frozen (retrospective) or fresh (prospective) samples collected from symptomatic patients. Each Irozen (restospedito) or Troon (prosposor) in A and NOW Flu B and ImmunoCard STAT! Flu A & B (substantially equivalent devices), ImmunoCard STAT! Flu A & B and culture.

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Meridian Bioscience, Inc. Cincinnati, OH
The data in Table 6-2 shows the overall sensitivity of ImmunoCard STAT! Flu A&B in
The data in Table Station of Canainte and surph somnles . In Table 6-3, the The data in Table 6-2 shows the overall sensults. In Table 6-3, the data is futher divided to
comparison to culture with wash/aspirate and swabserty, In Table shoples, comparison to culture with wash/aspirate and swab samples. In Tuble of the many of the manages.
show the performance of prospective (freshly collected) versus retrospective

# Table 6-2 Performance of Wash/Aspirate Vs Swab samples

| Wash/Aspirate Specimens | ICS Flu A | | | Binax Flu A | | | ICS Flu B | | | Binax Flu B* | | |
|--------------------------|-----------|-----|-------|-------------|-----|-------|-----------|-----|-------|--------------|-----|-------|
| | Pos | Neg | Total | Pos | Neg | Total | Pos | Neg | Total | Pos | Neg | Total |
| Tissue Culture Pos (Std) | 35 | 4 | 39 | 34 | 5 | 39 | 4 | 3 | 7 | 4 | 3 | 7 |
| Tissue Culture Neg (Std) | 14 | 162 | 176 | 10 | 166 | 176 | 0 | 208 | 208 | 2 | 205 | 207 |
| Total | 49 | 166 | 215 | 44 | 171 | 215 | 4 | 211 | 215 | 6 | 208 | 214 |

*1 Binax Flu B Invalid

| Swab Specimens | ICS Flu A | | | Binax Flu A* | | | ICS Flu B | | | Binax Flu B* | | |
|--------------------------|-----------|-----|-------|--------------|-----|-------|-----------|-----|-------|--------------|-----|-------|
| | Pos | Neg | Total | Pos | Neg | Total | Pos | Neg | Total | Pos | Neg | Total |
| Tissue Culture Pos (Std) | 66 | 24 | 90 | 53 | 37 | 90 | 25 | 12 | 37 | 13 | 24 | 37 |
| Tissue Culture Neg (Std) | 9 | 329 | 338 | 4 | 333 | 337 | 0 | 391 | 391 | 31 | 359 | 390 |
| Total | 75 | 353 | 428 | 57 | 370 | 427 | 25 | 403 | 428 | 44 | 383 | 427 |

Total Total Total Total

## Table 6-3 Performance of prospective and retrospective samples

| Fresh samples -<br>Wash/Aspirate | ICS Flu A | | | Binax Flu A | | | ICS Flu B | | | Binax Flu B* | | |
|----------------------------------|-----------|-----|-------|-------------|-----|-------|-----------|-----|-------|--------------|-----|-------|
| | Pos | Neg | Total | Pos | Neg | Total | Pos | Neg | Total | Pos | Neg | Total |
| Tissue Culture Pos (Std) | 12 | 3 | 15 | 11 | 4 | 15 | 2 | 3 | 5 | 2 | 3 | 5 |
| Tissue Culture Neg (Std) | 8 | 110 | 118 | 5 | 113 | 118 | 0 | 128 | 128 | 1 | 126 | 127 |
| Total | 20 | 113 | 133 | 16 | 117 | 133 | 2 | 131 | 133 | 3 | 129 | 132 |

*1 Binax Flu B Invalid

| | | ICS Flu A | | | Binax Flu A* | | | ICS Flu B | | | Binax Flu B* | | |
|--------------------------|--|-----------|-----|-------|--------------|-----|-------|-----------|-----|-------|--------------|-----|-------|
| Fresh samples - Swab | | Pos | Neg | Total | Pos | Neg | Total | Pos | Neg | Total | Pos | Neg | Total |
| Tissue Culture Pos (Std) | | 29 | 11 | 40 | 19 | 21 | 40 | 19 | 6 | 25 | 9 | 16 | 25 |
| Tissue Culture Neg (Std) | | 2 | 229 | 231 | 2 | 228 | 230 | 0 | 246 | 246 | 0 | 245 | 245 |
| Total | | 31 | 240 | 271 | 21 | 249 | 270 | 19 | 252 | 271 | 9 | 261 | 270 |

*1 Binax Flu A Invalid, 1 Binax Flu B Invalid

| Frozen samples -<br>Wash/Aspirate | ICS Flu A | | | Binax Flu A | | | ICS Flu B | | | Binax Flu B | | |
|-----------------------------------|-----------|-----|-------|-------------|-----|-------|-----------|-----|-------|-------------|-----|-------|
| | Pos | Neg | Total | Pos | Neg | Total | Pos | Neg | Total | Pos | Neg | Total |
| Tissue Culture Pos (Std) | 23 | 1 | 24 | 23 | 1 | 24 | 2 | 0 | 2 | 2 | 0 | 2 |
| Tissue Culture Neg (Std) | 6 | 52 | 58 | 5 | 53 | 58 | 0 | 80 | 80 | 1 | 79 | 80 |
| Total | 29 | 53 | 82 | 28 | 54 | 82 | 2 | 80 | 82 | 3 | 79 | 82 |
| Frozen samples -- Swab | ICS Flu A | | | Binax Flu A | | | ICS Flu B | | | Binax Flu B | | |
| | Pos | Neg | Total | Pos | Neg | Total | Pos | Neg | Total | Pos | Neg | Total |
| Tissue Culture Pos (Std) | 37 | 13 | 50 | 34 | 16 | 50 | 6 | 6 | 12 | 4 | 8 | 12 |
| Tissue Culture Neg (Std) | 7 | 100 | 107 | 2 | 105 | 107 | 0 | 145 | 145 | 31 | 114 | 145 |
| Total | 44 | 113 | 157 | 36 | 121 | 157 | 6 | 151 | 157 | 35 | 122 | 157 |

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# Characterization of samples producing discordant results

The data collected during clinical trials is shown in the spreadsheets provided at the end of these The data collected Gunny Cliniour that 10-10-10-10-10-11
sections The results can be summarized as follows:

Table 6-4. Samples producing discrepant results.

| Sample<br>Number | ICSFAB<br>Results | Culture<br>Results | | Comments<br>PCR Results |
|------------------|-------------------|--------------------|-----------|-------------------------|
| 1-100 | Neg | A Pos | FN | Pos (Flu A) |
| 1-178 | Neg | A Pos | FN | Pos (Flu A) |
| 1-180 | Neg | B Pos | FN | Pos (Flu A) |
| 1-193 | Neg | B Pos | FN | Neg |
| 1-198 | Neg | A Pos | FN | Pos (Flu A) |
| 1-20 | A Pos | Neg | FP | Pos (Flu A) |
| 1-205 | Neg | B Pos | FN | No PCR |
| 1-206 | Neg | A Pos | FN | No PCR |
| 1-21 | Neg | A Pos | FN | No PCR |
| 1-216 | Neg | A Pos | FN | No PCR |
| 1-220 | Neg | A Pos | FN | No PCR |
| 1-224 | Neg | B Pos | FN | No PCR |
| 1-233 | Neg | A Pos | FP | No PCR |
| 1-24 | A Pos | Neg | FP | No PCR |
| 1-251 | Neg | B Pos | FN | Pos (Flu A) |
| 1-259 | Neg | A Pos | FN | Pos (Flu A) |
| 1-26 | Neg | A Pos | FN | Pos (Flu A) |
| 1-263 | Neg | A Pos | FN | No PCR |
| 1-269 | Neg | B Pos | FN | No PCR |
| 1-27 | Neg | A Pos | FN | No PCR |
| 1-270 | Neg | A Pos | FN | Pos (Flu A) |
| 1-271 | A Pos | Neg | FP | Pos (Flu A) |
| 1-278 | Neg | B Pos | FN | Pos (Flu A) |
| 1-288 | Neg | A Pos | FN | No PCR |
| 1-289 | Neg | B Pos | FN | No PCR |
| 1-29 | Neg | A Pos | FN | No PCR |
| 2-08 | A Pos | Neg | FP | Pos (Flu A) |
| 2-101 | A Pos | Neg | FP | No PCR |
| 2-106 | A Pos | Neg | FP | Pos (Flu A) |
| 2-15 | A Pos | Neg | FP | Pos (Flu A) |
| 2-52 | A Pos | Neg | FP | Pos (Flu A) |
| 2-54 | A Pos | Neg | FP | Pos (Flu A) |
| 2-61 | Neg | A Pos | FN | Pos (Flu A) |
| 2-62 | A Pos | Neg | FP | Pos (Flu A) |
| 3-120 | Neg | B Pos | FN | Pos (Flu A) |
| 3-121 | Neg | B Pos | FN | Pos (Flu A) |
| 3-123 | Neg | B Pos | FN | No PCR |
| 3-14 | Neg | A Pos | FN | Pos (Flu B) |
| 3-20 | Neg | A Pos | FN | No PCR |
| 3-22 | A Pos | Neg | FP | Pos (Flu B) |
| 3-31 | A Pos | Neg | FP | Pos (Flu B) |
| 3-4 | Neg | A Pos | FN | Pos (Flu B) |
| 3-48 | A Pos | Neg | FP | No PCR |
| 3-5 | Neg | A Pos | FN | Pos (Flu B) |
| 3-52 | A Pos | Neg | FP | Pos (Flu B) |
| 3-8 | Neg | A Pos | FN | No PCR |
| 3-82 | A Pos | Neg | FP | Pos (Flu B) |
| 4-137 | Neg | A Pos | FN | Pos (Flu B) |
| 4-142 | A Pos | Neg | FP | Pos (Flu A) |
| 4-152 | Neg | B Pos | FN | Pos (Flu A) |
| 4-171 | Neg | A Pos | FN | Pos (Flu A) |
| 4-180 | Neg | B Pos | FN | Pos (Flu A) |
| 4-182 | Neg | B Pos | FN | Pos (Flu A) |
| 4-188 | A Pos | Neg | FP | No PCR |
| 4-191 | A Pos | Neg | FP | No PCR |
| Sample<br>Number | ICSFAB<br>Results | Culture<br>Results | | Comments<br>PCR Results |
| 4-216 | A Pos | Neg | FP | No PCR |
| 4-39 | A Pos | Neg | FP | No PCR |
| 4-52 | A Pos | Neg | FP | Pos (Flu A) |
| 4-58 | A Pos | Neg | FP | Neg |
| 4-64 | Neg | A Pos | FN | Pos (Flu A) |
| 4-68 | Neg | A Pos | FN | No PCR |
| 4-69 | Neg | A Pos | FN | No PCR |
| 4-70 | Neg | A Pos | FN | No PCR |
| 4-71 | Neg | B Pos | FN | Neg |
| 4-82 | A Pos | Neg | FN | Neg |
| 4-89 | Neg | A Pos | FN | Neg |
| 2-25 | A Pos | Overgrown | Overgrown | Pos (Flu A) |
| 2-31 | A Pos | Overgrown | Overgrown | Pos (Flu A) |
| 2-50 | Neg | Overgrown | Overgrown | Neg |
| 2-57 | Neg | Overgrown | Overgrown | Neg |
| 2-60 | A Pos | Overgrown | Overgrown | Pos (Flu A) |

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#### Meridian Bioscience, Inc. Cincinnati, OH

#### Table 6-4 Continued

Legend: FN = false negative, FP = false positive

#### Reproducibility

A reproducibility panel, consisting of 14 coded specimens, were sent to three climical sites. Ten of these A reproducibility parti, consisting of 14 coded specificals, word NOW Flu B as positive. Two samples were classilled by the predicate devices binese from A & B and two samples were additional samples were at the limit of Geloor of in intersours of rative result. Even though the tital sites negalive. The samples were expected to produce a positive the strength of a positive readion that was were instructed to grade reactions, there were no ontent regaranty and inter-assay reproducibility of 100%.

#### High dose hook effect

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

#### CONCILUSIONS

ImmunoCard STAT! Flu A & B:

- Our CTAT: ha Fra L.
Can be used reliably for the rapid detection of influenza B antigens in human 1. respiratory specimens
- Performs similarly to the predicate devices Binax NOW Flu A and NOW Flu B. 2.

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| | | Clinical Site 1 | | | Clinical Site 2 | | | Clinical Site 3 | | |
|------------------------|-------|-----------------|-------|-------|-----------------|-------|-------|-----------------|-------|--|
| Sample ID | Day 1 | Day 2 | Day 3 | Day 1 | Day 2 | Day 3 | Day 1 | Day 2 | Day 3 | |
| 1 LP Flu A | 3 | 8 | 7 | 2 | 1 | 5 | 4 | Pos | 5 | |
| 2 LP Flu A | 3 | 3 | 3 | 2 | 0.5 | 1 | 3.5 | Pos | 4 | |
| 3 LP Flu B | 0.5 | 1 | 1 | 0.5 | 0.5 | 0.5 | 3 | 1 | 2 | |
| 4 LP Flu B | 3 | 4 | 4 | 1 | 2 | 3 | 6 | Pos | 5 | |
| 5 MP Flu A | 4 | 5 | 4 | 4 | 3 | 5 | 5 | Pos | 6 | |
| 6 MP Flu A | 4 | 3 | 4 | 2 | 3 | 3 | 6.5 | 2 | 1 | |
| 7 MP Flu B | 3 | 4 | 3 | 3 | 3 | 4 | 4.5 | Pos | 5 | |
| 8 MP Flu B | 5 | 5 | 6 | 3 | 5 | 4 | 5 | 6 | 6.5 | |
| 9 HP Flu A | 7 | 6 | 6 | 7 | 5 | 5 | 6.5 | 2 | 6.5 | |
| 10 HP Flu B | 9 | 9 | 8 | 7 | 8 | 8 | 9 | 10 | 10 | |
| 11 N | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
| 12 N | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
| 13 Limit of detect A | 1 | 2 | 2 | 1 | 0.5 | 1 | 2.5 | 2 | 1.5 | |
| 14 Limit of detect B | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | |
| Total positive score | 42.5 | 50.0 | 48.0 | 32.5 | 31.5 | 39.5 | 55.5 | 24 | 53.5 | |
| Average positive score | 3.5 | 4.2 | 4.0 | 2.7 | 2.6 | 3.3 | 4.6 | 3.4 | 4.5 | |
| Percent correlation | 100% | 100% | 100% | 100% | 100% | 100% | 100% | 100% | 100% | |

.

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

Percent (x)relation
Legend: I.P = low positive, MP = moderate positive, HP = high positive, N = negative,

.

:

.

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Image /page/8/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is circular and contains the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. In the center of the circle is an abstract symbol that resembles an eagle.

MAR 16 2005

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

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

k041626 Re:

K041620
Trade/Device Name: ImmunoCard STAT! Flu A&B PLUS Regulation Number: 21 CFR 866.3330 Regulation Name: Influenza virus serological reagents Regulatory Class: Class I Product Code: GNX Dated: February 28, 2005 Received: March 1, 2005

Dear Ms. Rolih:

We have reviewed your Section 510(k) premarket notification of intent to market the devices indication we have reviewed your Section > ro(t) premained is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate for use stated in the encrosule) to regally manat date of the Medical Device American be on to commerce provide way 28, 1976, the encordance with the provisions of the Federal Food. Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). and Costlience Act (Act) that do not require the general controls provisions of the Act. The f ou may, therefore, market the device, editor equirements for annual registration, listing of general controls provisions of the res, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), If your device is classified (360 dooro) in the subject to subject and affecting your device It may be subject to such additional comiser Listions (CFR), Paris 800 to 895. In addition, FDA can be found in This 21, Cours announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean Please be advised that I DA 3 issuants of rour device complies with other requirements of the Act that I DA has made a decerminations administered by other Federal agencies. You must of any recetal statutes and regaranents ancluding, but not limited to: registration and listing (21 Comply with an the Ave Brequire. Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

{9}------------------------------------------------

Page 2 -

This letter will allow you to begin marketing your device as described in your Section 510(k) This letter will allow you to begin marketing war antial equivalence of your device to a legally
premarket notification. The FDA finding of substantial equivalias and this p premarket notification. The PDA Inding of Subscantar of Marice and thus, permits your device to proceed to the market.

If you desire specific information about the application of labeling requirements to your device, and If you desire specific information advertising of your device, please contact the Office of In
or questions on the promotion and advertising of your device, please contact th or questions on the promotion and advertising of your active of 50-0484. Also, please note the Vitro Diagnosic Device Lyanadion and barey at (21). " (210FR Part 807.97).
regulation entitled, "Misbranding by reference to premarket notification and real regulation entitled, "Misoranting by reichers on your responsibilities under the Act from the You may obtain other general informations on your reopsitions of the manager Division of Siman [phone] or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html

Sincerely yours,

Saly, a Forg

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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# Indications for Use ImmunoCard STAT! Flu A&B PLUS

510(k) Number (if known): _K041626

Device Name:__________________________________________________________________________________________________________________________________________________________________

Indications For Use:

ImmunoCard STAT! Flu A&B PLUS is a rapid, qualitative, lateral-flow immunoassy for Immunocard STAT: TG A&D F EOS is a rapid, quality antigens in human nasal delecting both Innuenza / Cand Inndonia = a = a = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = aspirate, nasopharyngoal aspiratematic patients. It is recommended that all negative test results be confirmed by cell culture.

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

Over-The-Counter Use (21 CFR 801 Subpart C)

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Sallath
Division Sign-Off

Page 1 of

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) _______________________________________________________________________________________________________________________________________________________________________ K641626