GENZYME OSOM INFLUENZA A & B TEST

K051244 · Genzyme Corp. · PSZ · Feb 21, 2006 · Microbiology

Device Facts

• Record ID: K051244
• Device Name: GENZYME OSOM INFLUENZA A & B TEST
• Applicant: Genzyme Corp.
• Product Code: PSZ · Microbiology
• Decision Date: Feb 21, 2006
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3328
• Device Class: Class 2
• Attributes: Pediatric

Intended Use

The OSOM Influenza A&B Test is an in vitro diagnostic immunochromatographic assay intended for the qualitative detection of influenza A and influenza B viral nucleoprotein antigens from nasal swab specimens in symptomatic patients. It is intended to aid in the rapid differential diagnosis of influenza A and/or B viral infections. This test is not intended for the detection of influenza C. viruses. A negative test is presumptive and it is recommended these results be confirmed by cell culture. Cross-reactivity with respiratory viruses other than influenza viruses has not been evaluated. The user is responsible for determining the cross-reactivity of other respiratory viruses with this test.

Device Story

Lateral flow immunochromatographic assay for rapid differential diagnosis of influenza A and B. Input: nasal swab specimen solubilized in extraction buffer. Principle: viral nucleoproteins migrate along a membrane; bind to colloidal gold-conjugated mouse monoclonal IgG antibodies; captured by secondary mouse anti-influenza antibodies on nitrocellulose. Output: visual pink/purple test lines (A, B, or both) and a control line. Used in clinical laboratories, health clinics, and physician offices by healthcare personnel. Provides rapid (10-minute) qualitative results to aid clinical decision-making; negative results require culture confirmation. Benefits: rapid identification of influenza A/B infections to guide patient management.

Clinical Evidence

Clinical trial (2004-2005) with 383 subjects (pediatric and adult) presenting with flu-like symptoms. Compared to cell culture. Influenza A: 73.8% sensitivity (95% CI 64.4-81.9%), 96.4% specificity (95% CI 93.4-98.2%). Influenza B: 60.0% sensitivity (95% CI 45.2-73.6%), 96.4% specificity (95% CI 93.8-98.1%). Reproducibility study across four sites showed 97% accuracy for Flu A and 94% for Flu B.

Technological Characteristics

Lateral flow immunochromatographic assay. Components: test stick, extraction buffer. Detection: mouse monoclonal IgG antibodies conjugated to colloidal gold. Membrane: nitrocellulose coated with mouse anti-influenza A/B antibodies. Visual readout: pink to purple lines. Standalone device; no instrumentation required.

Indications for Use

Indicated for qualitative detection of influenza A and B viral nucleoprotein antigens in symptomatic patients using nasal swab specimens. Not for influenza C detection. Negative results are presumptive and require confirmation 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

• Quidel QuickVue™ Influenza A+B Test (K031899)

Submission Summary (Full Text)

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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

A. 510(k) Number:
K052499

B. Purpose for Submission:
New device(s)

C. Measurand:
Influenza A and B nucleoprotein antigens

D. Type of Test:
Rapid chromatographic immunoassay that differentiates influenza A from influenza B virus

E. Applicant:
Genzyme Corporation

F. Proprietary and Established Names:
® Influenza OSOM A&B Test

G. Regulatory Information:
1. Regulation section: 21CFR 866.3330; Influenza Virus Serological Reagents
2. Classification: Class: I
3. Product code: GNX, Antigens, CF, including CF controls, Influenza A, B, and C.
4. Panel: 83 Microbiology

H. Intended Use:
The OSOM Influenza A&B Test is an in vitro diagnostic immunochromatographic assay intended for the qualitative detection of influenza A and influenza B viral antigens from nasal swab specimens. It is intended to aid in the rapid differential diagnosis of influenza A and/or B viral infections. A negative test is presumptive and should be confirmed by cell culture.

Cross-reactivity with other respiratory viruses in this assay has not been

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evaluated. The user is responsible for determining the cross-reactivity of other respiratory viruses with this test.

2. Indication(s) for use:
The OSOM Influenza A&B Test is an in vitro diagnostic immunochromatographic assay intended for the qualitative detection of influenza A and influenza B viral antigens from nasal swab specimens. It is intended to aid in the rapid differential diagnosis of influenza A and/or B viral infections. A negative test is presumptive and should be confirmed by cell culture.

Cross-reactivity with other respiratory viruses in this assay has not been evaluated. The user is responsible for determining the cross-reactivity of other respiratory viruses with this test.

3. Special conditions for use statement(s):
For prescription use

4. Special instrument requirements:
None

I. Device Description:
The OSOM Influenza A&B Test consists of a test stick that separately detects influenza A and B. The test procedure requires the solubilization of the nucleoproteins from a swab by mixing the swab in Extraction Buffer. The test stick is then placed in the sample mixture, which then migrates along the membrane surface. If influenza A and/or B viral antigens are present in the sample, it will form a complex with mouse monoclonal IgG antibodies to influenza A and/or B nucleoproteins conjugated to colloidal gold. The complex will then be bound by another mouse anti-influenza A and/or B antibody coated on the nitrocellulose membrane. A pink to purple control line must appear in the control region of the stick for results to be valid. The appearance of a second and possibly a third light pink to purple line will appear in the test line region indicating an A, B or A and B positive result.

J. Substantial Equivalence Information:

1. Predicate device name(s):
Viral cell culture, Quidel QuickVue® Influenza A+B Test

2. Predicate 510(k) number(s):
Comparison with predicate:

Table 1: Summary of Device Similarities and Differences

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| | OSOM Influenza A&B Test | Quidel QuickVue® Influenza A+B Test |
| --- | --- | --- |
| Intended use | Intended for the qualitative detection of influenza A and influenza B viral antigens from nasal swab specimens. It is intended to aid in the rapid differential diagnosis of influenza A and/or B viral infections. The test is for use in clinical laboratories, health clinics, and physician office laboratories. | Intended for the rapid, qualitative detection of influenza type A and influenza type B antigens from nasal swab, nasal wash and/or nasal aspirate specimens. This test is intended for use as an aid in the rapid differential diagnosis of acute influenza type A and type B virus infection. |
| Assay Format | Lateral flow immunoassay | Lateral flow immunoassay |
| Specimen | - nasal swabs | - nasal swabs
- nasal wash
- nasal aspirate |
| Antibodies (labeled and capture) | Mouse monoclonals | Mouse monoclonals |
| Conjugate | Colloidal gold | Latex |
| Objective Test Line | Pink to purple line | Red line |
| Internal Control | Yes – red line | Yes – blue line |
| Time To Result | 10 minutes | 10 minutes |

# K. Standard/Guidance Document Referenced (if applicable):

Not applicable

# L. Test Principle:

Immunochromatographic assay

# M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

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Assay Reproducibility

A reproducibility proficiency study was conducted to demonstrate that the OSOM Influenza A&B Test will perform acceptably in the hands of nurses, nurse practitioners and physicians' office personnel. A panel of swabs including negative (no virus), strong negative (below the limit of detection), low (near the limit of detection) and mid viral levels for influenza A and B were coded and masked to the operators. This study was conducted with three operators at three health centers in the eastern United States (2 physician's offices and 1 clinic site) and at Genzyme Diagnostics. The overall accuracy was 97% for flu A and 94% for flu B. Two invalid tests were considered as incorrect results in each analysis.

| | Correct Response for Flu A | | Lower 95% Confidence Interval | Upper 95% Confidence Interval |
| --- | --- | --- | --- | --- |
| A - Strong Neg | 12/12 | 100.0% | 73.0% | 100.0% |
| A - Low | 23/24* | 95.8% | 78.9% | 99.9% |
| A - Med | 11/12* | 91.7% | 61.5% | 99.8% |
| B - Strong Neg | 12/12 | 100.0% | 73.0% | 100.0% |
| B - Low | 23/24 | 95.8% | 78.9% | 99.9% |
| B - Med | 11/12 | 91.7% | 61.5% | 99.8% |
| AB - Med | 12/12 | 100.0% | 73.0% | 100.0% |
| Negative | 48/48 | 100.0% | 92.5% | 100.0% |
| Total | 152/156* | 97.4% | 93.6% | 99.3% |
| | Correct Response for Flu B | | Lower 95% Confidence Interval | Upper 95% Confidence Interval |
| A - Strong Neg | 12/12 | 100.0% | 73.0% | 100.0% |
| A - Low | 23/24* | 95.8% | 78.9% | 99.9% |
| A - Med | 11/12* | 91.7% | 61.5% | 99.8% |
| B - Strong Neg | 11/12 | 91.7% | 61.5% | 99.8% |
| B - Low | 21/24 | 87.5% | 67.6% | 97.3% |
| B - Med | 11/12 | 91.7% | 61.5% | 99.8% |
| AB - Med | 12/12 | 100.0% | 73.0% | 100.0% |
| Negative | 46/48 | 95.8% | 85.7% | 99.5% |
| Total | 147/156* | 94.2% | 89.3% | 97.3% |

*invalids due to insufficient volume or no control line.

b. Linearity/assay reportable range:
Not applicable

c. Traceability, Stability, Expected values (controls, calibrators, or methods):
Not applicable

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d. Detection limit:

Analytical Sensitivity

Dilutions of influenza A Kitakyushyu/159/93 (H3N2) and for influenza B Lee/40 virus were run in triplicate on three lots of the OSOM Influenza A&B Test. The approximate detection limits of the OSOM Influenza A&B Test are 4.4 x 10^{4} TCID_{50}/test for influenza A and 1.44 x 10^{5} TCID_{50}/test for influenza B.

Not applicable

e. Analytical specificity:

The OSOM Influenza A&B Test was evaluated with 25 bacterial isolates. Bacterial isolates were tested at a concentration of approximately 10^{8} cfu/mL. Very high levels of Staphylococcus aureus (>9x10^{8} cfu/mL) produced a positive result. All other bacteria listed gave negative responses. Cross-reactivity with other known respiratory viruses was not evaluated. Only influenza isolates were tested.

Bacterial Panel:

Acinetobacter calcoaceticus

Bordetella pertussis

Candida albicans

Corynebacterium diphteriae

Enterococcus faecalis

Enterococcus gallinarum

Escherichia coli

Haemophilus influenza

Klebsiella pneumoniae

Legionella pneumophilia

Moraxella catarrhalis

Mycobacterium avium

Mycobacterium tuberculosis

Neisseria meningitidis

Proteus mirabilis

Proteus vulgaris

Pseudomonas aeruginosa

Serratia marcescens

Staphylococcus aureus

Staphylococcus epidermidis

Streptococcus Group A

Streptococcus Group B

Streptococcus mutans

Streptococcus pneumoniae

Torulopsis glabrata

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# Influenza A/B Panel testing

A total of 46 human and animal influenza strains were tested with the OSOM Influenza A&B test. Viral titers $(\mathrm{TCID}_{50})$ for A/Kitakyushu/159/93 (H3N2) and B/Lee/40 were determined by inoculating MDCK cells, followed by standard procedures for cell culture viral assays. Aliquots of these controls with known $\mathrm{TCID}_{50}$ were then used to establish a standard curve in an ELISA assay. The concentrations of other influenza viruses were determined indirectly using the ELISA assay after the viruses had been inactivated. Influenza viruses were tested at an ELISA estimated $\mathrm{TCID}_{50}$ as listed in the table below.

All influenza virus isolates gave positive results with the test line at the expected location for the A, B and animal (positive for influenza A) isolates.

| Influenza A strains: | Sub-type | Estimated ELISA TCID50/mL |
| --- | --- | --- |
| Beijing/262/95 | H1N1 | 8.25E+07 |
| Brazil/11/78 | H1N1 | NA |
| Chile/1/83 | H1N1 | NA |
| New Jersey/8/76 | H1N1 | 2.78E+08 |
| Taiwan/1/86 | H1N1 | 3.47E+07 |
| Guizhou/54/89 | H3N2 | 7.54E+07 |
| OMS/5389/88 | H3N2 | NA |
| Beijing/32/92 | H3N2 | 3.97E+06 |
| England/427/88 | H3N2 | 4.73E+07 |
| Johannesburg/33/94 | H3N2 | 1.61E+07 |
| Leningrad/360/86 | H3N2 | 2.50E+06 |
| Mississippi/1/85 | H3N2 | NA |
| Philippines/2/82 | H3N2 | 9.75E+07 |
| Shangdong/9/93 | H3N2 | 1.67E+08 |
| Shanghai/16/89 | H3N2 | 3.49E+08 |
| Shanghai/24/90 | H3N2 | NA |
| Sichuan/2/87 | H3N2 | NA |
| Kitakyushyu/159/93 | H3N2 | 3.19E+08 |
| Akita/1/94 | H3N2 | 2.90E+08 |
| Beijing/262/95 | H1N1 | 1.71E+08 |
| Yamagata/32/89 | H1N1 | 7.28E+07 |
| New Caledonia/20/99 | H1N1 | 6.86E+07 |
| Panama/2007/99 | H3N2 | 1.40E+08 |
| Wyoming/03/03 | H3N2 | 7.40E+06 |
| Fujian/411/02 | H3N2 | 6.12E+07 |
| Influenza B strains: | Sub-type | Estimated ELISA TCID50/mL |
| --- | --- | --- |
| Ann Arbor/1/86 | | NA |
| Beijing1/87 | | 1.04E+07 |
| Guangdong/120/2000 | | 6.44E+07 |
| Hongkong/8/73 | | 1.74E+07 |
| Panama/45/90 | | 3.79E+07 |
| Singapore/222/79 | | 4.84E+07 |
| Yamagata/16/88 | | 1.78E+07 |
| Lee/40 | | 2.13E+08 |
| Mie/1/93 | | 4.84E+07 |
| Guangdong/05/94 | | 1.27E+07 |
| Johannesburg/5/99 | | 5.87E+07 |
| Shandong/7/97 | | 4.41E+07 |
| Shanghai/361/2002 | | NA |
| Animal influenza strains: | Sub-type | Estimated ELISA TCID50/mL |
| --- | --- | --- |
| A/Duck/Singapore-Q/F119-3/97 | H5N3 | 1.65E+08 |
| A/Equine/Prague/56 | H7N7 | 5.37E+06 |
| A/Duck/Wisconsin/1120/82 | H5N3 | 2.30E+08 |
| A/Hong Kong/483/97 | H5N1 | 1.06E+08 |
| A/Hong Kong/213/2003 | H5N1 | 1.84E+08 |
| A/Turkey/Ontario/71 | H7N3 | 8.12E+07 |
| A/Mallard/Wisconsin/479/79 | H7N3 | 2.08E+08 |
| A/Mallard/Saskatchewa | H7N3 | 2.46E+08 |

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f. Assay cut-off:

Not applicable

2. Comparison studies:

a. Method comparison with gold standard: See clinical studies.

b. Matrix comparison :

Not applicable

3. Clinical studies: A clinical trial was conducted during the 2004-2005 flu season in the United States at sites located in the east, central and west regions to establish the clinical sensitivity and clinical specificity of the OSOM Influenza A&B Test in detecting influenza A and influenza B antigens in nasal swab specimens. Sites included family practice and pediatric offices, emergency departments and clinics. All clinical samples were collected from patients with flu-like symptoms including fever, dry cough and myalgia. Nasal swab specimens were collected from a total of 383 subjects enrolled in the study. Of the 383 samples, 132 samples were from pediatric subjects (2-19 years) and 251 samples were from adults (≥ 20 years). The OSOM Influenza A&B Test was compared to cell culture to determine the comparative clinical sensitivity and clinical specificity for detection of influenza A and influenza B in nasal swab specimens

a. Clinical Sensitivity and specificity:

Comparison of OSOM Influenza A&B Test to Cell culture: Nasal Swab

| Flu A
OSOM
Influenza A&B | Culture | | | |
| --- | --- | --- | --- | --- |
| | A+ | Negative | Total | |
| A+ | 79 | 9^{1} | | 88 |
| A+B+ | 0 | 1^{2} | | 1 |
| Negative | 28^{3} | 266 | | 294 |
| | | | | |
| Total | 107 | 276 | | 383 |

Clinical sensitivity: 73.8% (79/107)<br/>
(95% CI 64.4% - 81.9%)

Clinical specificity: 96.4%. (266/276)<br/>
(95% CI 93.4% - 98.2%)

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| Flu B
OSOM
Influenza
A&B | Culture | | | |
| --- | --- | --- | --- | --- |
| | B+ | Negative | Total | |
| B+ | 30 | 11^{4} | | 41 |
| A+B+ | 0 | 1^{5} | | 1 |
| Negative | 20^{6} | 321 | | 341 |
| | | | | |
| Total | 50 | 333 | | 388 |

Clinical sensitivity: 60.0% (30/50)<br/>(95% CI 45.2-73.6%)

Clinical specificity: 96.4% (321/333)<br/>(95% CI 93.8% - 98.1%)

c. Other clinical supportive data (when a. and b. are not applicable):<br/>Not applicable

4. Clinical cut-off:<br/>Not applicable

5. Expected values/Reference range:<br/>Not applicable

N. Proposed Labeling:<br/>The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

O. Conclusion:<br/>The submitted information in this premarket notification is complete and supports a substantial equivalence decision.