ImmunoCard STAT! HpSA

K153661 · Meridian Bioscience, Inc. · LYR · Mar 14, 2016 · Microbiology

Device Facts

• Record ID: K153661
• Device Name: ImmunoCard STAT! HpSA
• Applicant: Meridian Bioscience, Inc.
• Product Code: LYR · Microbiology
• Decision Date: Mar 14, 2016
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3110
• Device Class: Class 1

Indications for Use

The ImmunoCard STAT! HpSA is a rapid in vitro qualitative procedure for the detection of Helicobacter pylori antigens in human stool. The stool antigen detection is intended to aid in the diagnosis of H. pylori infection and to demonstrate loss of H. pylori stool antigen following treatment. Conventional medical practice recommends that testing by any method to confirm loss of antigen be done at least four weeks following completion of therapy.

Device Story

Rapid lateral flow immunoassay for qualitative detection of H. pylori antigens in human stool. Device consists of chromatography strips in plastic frame; utilizes dissociated monoclonal anti-H. pylori capture antibody and latex-conjugated detector antibodies. User adds stool sample to diluent; dispenses into device window. Antigen binds to detector antibody-latex conjugate; complex captured by membrane-bound antibody, forming visible pink/red line. Control line (blue) confirms adequate flow. Visual interpretation by clinician. Results aid in H. pylori infection diagnosis and post-treatment monitoring. Benefits include rapid, point-of-care assessment of infection status.

Clinical Evidence

Bench testing only. Reproducibility study across three sites using 90 contrived specimens showed 98.9% total agreement for moderate positives and 100% for low positives. Method comparison study against predicate device (n=150) showed 98.3% positive agreement and 98.9% negative agreement. Analytical specificity testing confirmed no cross-reactivity with 34 bacterial, viral, or yeast strains. Interfering substances (antacids, blood, fat, etc.) showed no effect on results.

Technological Characteristics

Rapid immunochromatographic assay for qualitative detection of H. pylori antigens in stool. Device is a standalone, non-automated diagnostic test.

Indications for Use

Indicated for the qualitative detection of Helicobacter pylori antigens in human stool to aid in the diagnosis of H. pylori infection and to monitor the loss of antigen following treatment in patients.

Regulatory Classification

Identification

Campylobacter fetus serological reagents are devices that consist of antisera conjugated with a fluorescent dye used to identify Campylobacter fetus from clinical specimens or cultured isolates derived from clinical specimens. The identification aids in the diagnosis of diseases caused by this bacterium and provides epidemiological information on these diseases. Campylobacter fetus is a frequent cause of abortion in sheep and cattle and is sometimes responsible for endocarditis (inflammation of certain membranes of the heart) and enteritis (inflammation of the intestines) in humans.

Submission Summary (Full Text)

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510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
ASSAY ONLY TEMPLATE

A. 510(k) Number:
K153661

B. Purpose for Submission:
To seek clearance for a modification of the ImmunoCard STAT! HpSA

C. Measurand:
H. pylori antigen

D. Type of Test:
Lateral flow immunoassay

E. Applicant:
Meridian Bioscience Inc.

F. Proprietary and Established Names:
ImmunoCard STAT! HpSA

G. Regulatory Information:
1. Regulation section:
21 CFR Part 866.3110 Campylobacter fetus serological reagents
2. Classification:
Class I
3. Product code:
LYR
4. Panel:
83, (Microbiology)

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H. Intended Use:

1. Intended use(s):

The ImmunoCard STAT! HpSA is a rapid in vitro qualitative procedure for the detection of *Helicobacter pylori* antigens in human stool. The stool antigen detection is intended to aid in the diagnosis of *H. pylori* infection and to demonstrate loss of *H. pylori* stool antigen following treatment. Conventional medical practice recommends that testing by any method to confirm loss of antigen be done at least four weeks following completion of therapy.

2. Indication(s) for use:

Same as the Intended Use.

3. Special conditions for use statement(s):

Not applicable

4. Special instrument requirements:

Not applicable

I. Device Description:

The ImmunoCard STAT! HpSA is a rapid lateral flow immunoassay. It consists of chromatography strips impregnated with dissociated monoclonal anti-*H. pylori* antibody as the capture antibody, red latex-conjugated detector antibody and blue latex-conjugated anti-protein as the detector antibodies for tests and controls respectively. Each strip is enclosed in a plastic frame with a window. The kit also contains a positive control which is a dilute suspension of inactivated *H. pylori* in a buffered solution containing <0.1% sodium azide as a preservative, and a specimen diluent which is a buffered salt solution. This device contained modifications in the monoclonal antibodies (dissociated monoclonal capture antibody) used on the capture and detector sides of the assay and the formulation of the sample and internal control diluent.

J. Substantial Equivalence Information:

1. Predicate device name(s):

ImmunoCard STAT! HpSA

2. Predicate 510(k) number(s):

K032222

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3. Comparison with predicate:

| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| | K153661 | K032222 |
| Intended Use | The ImmunoCard STAT! HpSA is a rapid in vitro qualitative procedure for the detection of Helicobacter pylori antigens in human stool. The stool antigen detection is intended to aid in the diagnosis of H. pylori infection and to demonstrate loss of H. pylori stool antigen following treatment. Conventional medical practice recommends that testing by any method to confirm loss of antigen be done at least four weeks following completion of therapy. | Same |
| Sample Type | Human stool samples (solid, semisolid, and liquid) | Same |
| Assay | Qualitative | Same |
| Assay Target | Helicobacter pylori antigens in human stool | Same |
| Reading Method | Visual interpretation of test results | Same |
| Fundamental Scientific Technology | Rapid immunochromatographic assay | Same |
| Reagents Provided | ICS HpSA Test Device Sample Diluent Positive Control | Same |
| Differences | | |
| --- | --- | --- |
| Item | Device K153661 | Predicate K032222 |
| Capture Antibody | Modified monoclonal anti-H. pylori antibody | Monoclonal anti-H. pylori antibody |

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

Not applicable

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L. Test Principle:

ImmunoCard STAT! HpSA uses capture solid phase technology to detect the presence of antigen in test specimens. To perform the test, patient stool is added to the Sample Diluent using the applicator stick that is part of the Sample Diluent Vial. The diluted stool sample (approximately a 1 in 10 dilution) is dispensed through the tip of the Sample Diluent Vial into the round sample window of the device. H. pylori antigen, if present in the diluted sample, binds to the detector antibody-latex conjugate as the sample moves through the device. The capture, dissociated monoclonal, antibody which is bound to the assay membrane at the reading window, binds the antigen-antibody latex complex. The result is a visible pink/red line. When no antigen is present, no complex is formed and no pink/red line will appear at the test position of the central window.

A control line, appearing at the control position in the test window, shows whether adequate flow has occurred through the device during a test run. The control line is derived from protein of non-mammalian origin. Blue latex particles are conjugated with a monoclonal antibody to this non-mammalian animal protein. Together they migrate as the monoclonal antibody/blue latex complex during the incubation step. A blue line at the control position on the device should be present each time a specimen or control is tested. If no blue control line is seen, the test is considered invalid.

M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

Studies were performed to demonstrate the inter-laboratory and intra-laboratory reproducibility of the modified device. Testing was performed by two technologists in three separate laboratories over the course of five days. Each technologist was supplied with a panel of coded specimens prior to testing. The specimens were diluted and tested according to the package insert method.

Contrived specimen panels were prepared by spiking H. pylori into negative pooled fecal specimens at antigen concentrations above, near and below the assay limit of detection for H. pylori antigen ATCC 43504. Each panel consisted of ten specimens: three moderately positive (6x LoD), three low positive (2x LoD), three high negative, and one natural negative specimen, that were randomly sorted within each panel. Two test kits were used during the study. The study results are summarized in Table 1. The reproducibility performance was acceptable.

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Table 1. Reproducibility Testing with the Modified Device

| Sample Type | Clinical Site 1 Percent Agreement | Clinical Site 2 Percent Agreement | Clinical Site 3 Percent Agreement | Total | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | | | Percent Agreement | | 95% CI | | |
| High Negative | 30/30 | 100.0 | 30/30 | 100.0 | 30/30 | 100.0 | 90/90 | 100.0 | 95.9 – 100.0 |
| Low Positive | 30/30 | 100.0 | 30/30 | 100.0 | 30/30 | 100.0 | 90/90 | 100.0 | 95.9 – 100.0 |
| Moderate Positive | 30/30 | 100.0 | 29/30 | 96.7 | 30/30 | 100.0 | 89/90 | 98.9 | 94.0 – 99.8 |
| Negative | 10/10 | 100.0 | 9/10 | 90.0 | 10/10 | 100.0 | 29/30 | 96.7 | 83.3 – 99.4 |
| Negative Control | 10/10 | 100.0 | 10/10 | 100.0 | 10/10 | 100.0 | 30/30 | 100.0 | 88.6 - 100.0 |
| Positive Control | 10/10 | 100.0 | 10/10 | 100.0 | 10/10 | 100.0 | 30/30 | 100.0 | 88.6 - 100.0 |

b. Linearity/assay reportable range:

Not applicable

c. Traceability, Stability, Expected values (controls, calibrators, or methods):

Not applicable

d. Detection limit:

The lower limit of detection of this assay is $64\mathrm{ng / mL}$ in tests with sonicated antigen prepared from H. pylori strain TV1970. This limit does not vary from formed (solid) to semi-solid stool.

e. Analytical specificity:

Cross reactivity

The specificity of ImmunoCard STAT! HpSA was tested with the following bacterial, viral and yeast strains. Positive and negative stools were spiked with $\geq 1\mathrm{X}10^{7}$ bacteria or yeast. Viruses were spiked at $10^{5}\mathrm{TCID}_{50} / \mathrm{mL}$ . None of the microorganisms tested yielded a positive result in the negative stool or interfered with detection of the positive stool. Both the negative and positive stool were positive when spiked with $H.$ pylori strain 43504.

Adenovirus Type 2

Adenovirus Type 40

Coxsackie Type B 1

Coxsackie Type B6

Echovirus Type 22

Feline calicivirus

Rotavirus

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Aeromonas hydrophila
Bacillus sp.
Campylobacter coli
Campylobacter jejuni
Candida albicans
Citrobacter freundii
Clostridium perfringens
Clostridium difficile (2)
Enterobacter cloacae
Enterococcus faecalis (2)
E. coli (2)
E. coli 0157:H7 (2)
E. fergusonii
Haemophilus influenzae
Helicobacter felis
Klebsiella pneumoniae
Proteus vulgaris
Pseudomonas aeruginosa
Salmonella dublin
Salmonella (Group B)
Salmonella hilversum
Salmonella minnesota
Salmonella typhimurium
Staphylococcus aureus
Staphylococcus aureus (Cowan I)
Staphylococcus epidermidis
Serratia liquifaciens
Shigella boydii
Shigella dysenteriae
Shigella flexneri
Shigella sonnei
Yersinia enterocolitica
Borrelia burgdorferi (Stool inoculated with antigen protein to a final cone. of 32 ug/mL)

## Interfering substances

The following substances were found to have no effect on results when present in stool at the concentrations indicated.

- Tums® Antacid (5 mg/mL)
- Tagamet® (5 mg/mL)
- Prilosec® (5 mg/mL)
- Mylanta® Antacid (1:20)
- Pepto-Bismol® (1:20)
- Barium sulfate (5%)
- Whole Blood (50%)
- Leukocytes (50%)
- Mucin (3.4%)
- Stearic acid/Palmitic acid (fecal fat) (4%)

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Hemoglobin (tarry stool) (12.5%)

f. Assay cut-off:

The assay cut off is 64 ng/mL of H. pylori antigen.

2. Comparison studies:

a. Method comparison with predicate device:

Method comparison testing was done to compare performance of the subject device using the modified dissociated monoclonal capture antibody to that of the predicate device using the unmodified monoclonal antibody.

The testing was performed with two operators who were blinded to the 150 prospectively collected and archived specimens. The specimens were collected from the intended use population. When tested with the predicate, the results were 57 positive and 93 negative. The results are summarized in Table 2 below.

Table 2. Performance Comparison between Modified Device and Predicate Device
| | ICS HpSA Predicate | | |
| --- | --- | --- | --- |
| ICS HpSA Modified | Positive | Negative | Total |
| Positive | 56 | 1 | 57 |
| Negative | 1 | 92 | 93 |
| Total | 57 | 93 | 150 |
| | | | 95% CI |
| Positive Agreement | 56/57(98.3%) | | 90.7-99.7% |
| Negative Agreement | 92/93(98.9%) | | 94.1-99.8% |

The percent positive and negative agreements compared to the predicate device were 98.3% (56/57, CI = 90.7 - 99.7%) and 98.9% (92/93, CI 94.1 - 99.8%), respectively. These results are acceptable.

b. Matrix comparison:

Not applicable

3. Clinical studies:

a. Clinical Sensitivity:

Not applicable

b. Clinical specificity:

Not applicable

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c. Other clinical supportive data:

Not applicable

4. Clinical cut-off:

See assay cut off above.

5. Expected values/Reference range:

Studies on the epidemiology of *H. pylori* have shown that this organism is present worldwide. The prevalence of *H. pylori* infection by various test methods in a given population can vary from 20% to 90%. In patients diagnosed with duodenal ulcers, however, it has been shown in every age group to be approximately 80%. The ImmunoCard STAT! HpSA test detects the presence of *H. pylori* antigens in human stool.

Expected values for a given population should be determined for each laboratory. The rate of positives may vary depending on geographic location, method of specimen collection, handling and transportation, test employed and general health environment of patient population under study.

N. Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

O. Conclusion:

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.