PREMIER PLATINUM HPSA

K980076 · Meridian Diagnostics, Inc. · LYR · May 12, 1998 · Microbiology

Device Facts

• Record ID: K980076
• Device Name: PREMIER PLATINUM HPSA
• Applicant: Meridian Diagnostics, Inc.
• Product Code: LYR · Microbiology
• Decision Date: May 12, 1998
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3110
• Device Class: Class 1

Intended Use

The Premier Platinum HpSA enzyme immunoassay (EIA) is an in virro qualitative procedure for the detection of Helicobacter pylori antigens in human stool. Test results are intended to aid in the diagnosis of H. pylori infection in adult patients.

Device Story

Premier Platinum HpSA is an in vitro diagnostic enzyme immunoassay (EIA) for detecting Helicobacter pylori antigens in human stool samples. The device uses microwells coated with polyclonal anti-H. pylori capture antibodies. Patient stool samples and peroxidase-conjugated polyclonal antibodies are added to the wells and incubated. After washing to remove unbound material, a substrate is added; color development indicates the presence of bound enzyme. Results are interpreted visually or spectrophotometrically by laboratory technicians. The test aids clinicians in diagnosing H. pylori infection in symptomatic adults, providing a non-invasive alternative to biopsy-based testing.

Clinical Evidence

Clinical evaluation involved 200 symptomatic adults across four sites (US, Canada, Italy). Reference methods included culture, rapid urease, histology, and urea breath test (UBT). Patients were positive if culture was positive or if two or more other tests were positive. The device demonstrated 96.1% sensitivity, 95.7% specificity, and 95.9% overall correlation with H. pylori infection status. Reproducibility was assessed via intra- and inter-assay testing across multiple concentrations.

Technological Characteristics

Sandwich enzyme immunoassay (EIA) using polyclonal anti-H. pylori capture antibodies. Output is qualitative colorimetric change, read visually or spectrophotometrically (single wavelength 450nm or dual 450-630nm). Requires laboratory equipment for incubation and washing. No electronic software or connectivity components.

Indications for Use

Indicated for the qualitative detection of Helicobacter pylori antigens in human stool to aid in the diagnosis of H. pylori infection in symptomatic adult 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.

Predicate Devices

• CLOtest, rapid urease test for biopsy specimens

Submission Summary (Full Text)

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MAY 1 2 1998

### 510(k) Summary

K980076

### Identification Information

### Submitter's Information:

#### Submitter's Name and Address:

Meridian Diagnostics, Inc. River Hills Drive Cincinnati, OH 45244

Phone Number: 1-800-543-1980

Contact Person: Allen D. Nickol, PhD Director of Scientific and Regulatory Affairs

Date Summary Prepared: May 5, 1998

Name of Device: Premier Platinum HpSA.

- Classification Name: Campylobacter pylori, 83LYR
# Predicate Equivalent Device:

CLOtest, rapid urease test for biopsy specimens.

#### Description of Device:

The Premier Platinum HpSA test utilizes polyclonal anti-H. pylori capture antibody adsorbed to microwells. Diluted patient samples and a peroxidase conjugated polyclonal antibody are added to the wells and incubated for one hour at room temperature. A wash is performed to remove unbound material. Substrate is added and incubated for ten minutes at room temperature. Color develops in the presence of bound enzyme. Stop solution is added and the results are interpreted visually or spectrophotometrically.

#### Intended Use:

The Premier Platinum HpSA enzyme immunoassay (EIA) is an in virro qualitative procedure for the detection of Helicobacter pylori antigens in human stool. Test results are intended to aid in the diagnosis of H. pylori infection in adult patients.

### Comparison with Predicate Devices:

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The following comparison of the use, technology, function and performance supports the Statement of Equivalence between the Premier Platinum HpSA test The differences in technology does not raise additional and the CLO test. concerns regarding safety and effectiveness. Safety and effectiveness are demonstrated to be substantially equivalent.

| Method | Premier HpSA | Rapid<br>Urease |
|----------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | Detection of H. pylori antigens in<br>patient stool | Detection of H. pylori associated<br>urease activity in biopsy<br>specimens |
| Results | Qualitative | Qualitative |
| Specimen Required | Stool | Gastric or Duodenal biopsy |
| Technology | Sandwich Enzyme Immunoassay | H. pylori urease catalyzed pH<br>change visualize by color change<br>indicator |
| Level of Skill<br>Required | Laboratory Technician | Gastroenterologist for biopsy and<br>laboratory technician for reading<br>result and QA. |
| Function | 1. Specimen diluted 1/3 and<br>added to well containing<br>rabbit anti-H. pylori capture<br>Ab.<br>2. One drop HRP-conjugated<br>detection Ab added.<br>3. Incubation 1 hr at room<br>temperature.<br>4. Wash 5 times.<br>5. Add 2 drops substrate.<br>6. Incubate 10 minutes at room<br>temperature.<br>7. Add one drop stop solution<br>and read visually or<br>spectrophotometrically | 1. Biopsy specimen place in<br>device and incubated at 30-<br>40°C for 3 hours. The keep at<br>room temperature up to 24<br>hours.<br>2. Read results for visual color<br>change. Negatives at 24 hours<br>if still yellow. Positive turn<br>pink, orange or magenta. |
| Interpretation | Pos/Neg read visually or<br>spectrophotometrically. Fixed<br>cutoff 0.140 single wavelength<br>(450nm) or 0.100 dual<br>wavelength (450-630nm) | Pos/Neg |
| Method | Premier HpSA | Rapid<br>Urease |
| Sensitivity | 96.2% (90.4-98.9%) | 95.4% (89.6-98.5%) |
| Specificity | 95.7% (89.5-98.8%) | 100.0% (96.4-100.0%) |
| Correlation | 96.0% (92.2-98.2%) | 97.6% (94.5-99.2%) |

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# Response Items, Round 2: K980076 Premier Platinum HpSA

... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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# Performance Characteristics:

The Premier Platinum HpSA test was evaluated on 200 symptomatic adults at one midwestern United States location, one site in Canada, and two sites in Italy. The patients studied had a wide cross-section of gastric pathologies noted, including: antral gastritis (n=81), antral gastropathy (n=25), antral erosions (n=24), esophagitis (n=21), duodenal ulcer (n=15), erosive duodemitis (n=10), GERD (n=10), "normal" (n=10), duodenitis (n=9), gastric ulcer (n=8), total stomach gastritis (n=6), hiatal hernia (n=6), Schatzki's ring (n=4), pyloric ulcer (n=2), and esophageal ulcer (n=1). HpSA test results were compared to diagnosis of H. pylori infection as judged by objective reference methods (culture, rapid urease, histology and UBT). Patients were considered positive if culture was positive, or if two or more of the other three tests were positive. Nine patients with negative or no culture results, and only one other test positive, were considered unevaluable. The HpSA test was 96.1% sensitive, 95.7% specific and showed 95.9% correlation with H. pylori infection. Confidence intervals were calculated by the exact binomial method.

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| Trial | Site | #1 |
|-------|------|----|
| | | |

| Test | | Diagnosis | | Sensitivity<br>± 95% CI | Specificity<br>± 95% CI | Positive PV<br>± 95% CI | Negative PV<br>± 95% CI | Correlation<br>± 95% CI |
|--------|--------|-----------|--------------|-------------------------|-------------------------|-------------------------|-------------------------|-------------------------|
| Method | Result | Infected | Not Infected | | | | | |
| HpSA | Pos | 17 | 3 | 94.4% | 91.4% | 85.0% | 97.0% | 92.5% |
| EIA | Neg | 1 | 32 | 72.7 to 99.9% | 76.9 to 98.2% | 62.1 to 96.8% | 84.2 to 99.9% | 81.8 to 97.9% |

Reference Methods: Histology, Rapid Urease, Breath Test. Readings Single and Dual Wavelength.

#### Trial Site #2

| Test | Diagnosis | | Sensitivity<br>± 95% CI | Specificity<br>± 95% CI | Positive PV<br>± 95% CI | Negative PV<br>± 95% CI | Correlation<br>± 95% CI | |
|--------|-----------|----------|-------------------------|-------------------------|-------------------------|-------------------------|-------------------------|----------------|
| Method | Result | Infected | Not Infected | | | | | |
| HpSA | Pos | 9 | 0 | 100.0% | 100.0% | 100.0% | 100.0% | 100.0% |
| EIA | Neg | 0 | 8 | 66.4 to 100.0% | 63.1 to 100.0% | 66.4 to 100.0% | 63.1 to 100.0% | 80.5 to 100.0% |
| | Equ | 0 | 0 | | | | | |

Reference Methods: Histology, Rapid Urease, Culture, Breath Test. Readings Single and Dual Wavelength.

#### Trial Site #3

| Test | | Diagnosis | | Sensitivity<br>± 95% CI | Specificity<br>± 95% CI | Positive PV<br>± 95% CI | Negative PV<br>± 95% CI | Correlation<br>± 95% CI |
|--------|--------|-----------|--------------|-------------------------|-------------------------|-------------------------|-------------------------|-------------------------|
| Method | Result | Infected | Not Infected | | | | | |
| HpSA | Pos | 44 | 0 | 97.8% | 100.0% | 100.0% | 96.0% | 98.6% |
| EIA | Neg | 1 | 24 | 88.2 to 99.9% | 85.8 to 100.0% | 92.0 to 100.0% | 79.6 to 99.9% | 92.2 to 100.0% |
| | Equ | 1 | 0 | | | | | |

Reference Methods: Histology, Rapid Urease, Culture, Breath Test. Readings Single Wavelength.

#### Trial Site #4

| Test | Diagnosis | | Sensitivity<br>± 95% CI | Specificity<br>± 95% CI | Positive PV<br>± 95% CI | Negative PV<br>± 95% CI | Correlation<br>± 95% CI | |
|--------|-----------|----------|-------------------------|-------------------------|-------------------------|-------------------------|-------------------------|---------------|
| Method | Result | Infected | Not Infected | | | | | |
| HpSA | Pos | 29 | 1 | 93.5% | 96.3% | 96.7% | 92.9% | 94.8% |
| EIA | Neg | 2 | 26 | 78.6 to 99.2% | 81.0 to 99.9% | 82.8 to 99.9% | 76.5 to 99.1% | 85.6 to 98.9% |
| | Equ | 2 | 0 | | | | | |

Reference Methods: Histology, Rapid Urease. Readings Dual Wavelength.

#### Compiled Data From All Sites

| Test | | Diagnosis | | Sensitivity<br>± 95% CI | Specificity<br>± 95% CI | Positive PV<br>± 95% CI | Negative PV<br>± 95% CI | Correlation<br>± 95% CI |
|--------|--------|-----------|--------------|-------------------------|-------------------------|-------------------------|-------------------------|-------------------------|
| Method | Result | Infected | Not Infected | | | | | |
| HpSA | Pos | 99 | 4 | 96.1% | 95.7% | 96.1% | 95.7% | 95.9% |
| EIA | Neg | 4 | 90 | 90.4 to 98.9% | 89.5 to 98.8% | 90.4 to 98.9% | 89.5 to 98.8% | 92.2 to 98.2% |
| | Equ | 3 | 0 | | | | | |

Additional Information/Non-clinical Test Results:

#### Reproducibility:

Reproducibility of the Premier Platinum HpSA test was determined using negative (n=2), low positive (n=2). medium postive (n=2) and high positive (n=1) samples tested in triplicate in three separate batches / runs at each of two separate sites. Intra- and inter-assay coefficients of variation were determined and are presented below (ranges are the results from two different specimens):

| | Intra-Assay<br>Reproducibility: Read at | Inter-Assay<br>Reproducibility: Read at |
|--|-----------------------------------------|-----------------------------------------|
|--|-----------------------------------------|-----------------------------------------|

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# Response Items, Round 2: K980076 Premier Platinum HpSA

| Specimen Type | 450nm | 450-630nm | Visible | 450nm | 450-630nm | Visible |
|---------------------|-----------------|------------------|---------|------------------|------------------|---------|
| Negative | 4.3% -<br>5.1% | 8.1% -<br>13.5% | 100% | 10.6% -<br>13.2% | 51.0% -<br>57.5% | 100% |
| Low<br>Positive | 9.2% -<br>14.8% | 11.0% -<br>16.6% | 100% | 15.3% -<br>27.9% | 18.0% -<br>32.9% | 100% |
| Medium<br>Positive | 8.8% -<br>9.0% | 9.6% -<br>9.6% | 100% | 17.6% -<br>19.3% | 19.7% -<br>19.7% | 100% |
| High<br>Positive | 11.2% | 11.6% | 100% | 19.8% | 20.0% | 100% |
| Negative<br>Control | 6.2% | 20.2% | 100% | 15.3% | 60.2% | 100% |
| Positive<br>Control | 2.2% | 1.9% | 100% | 22.8% | 23.9% | 100% |

### Frozen Stools:

Samples were tested on day 0, then put through four freeze / thaw cycles, being tested each time. The data supports four freeze / thaw cycles.

### Cross-Reactivity:

The specificity of Premier Platinum HpSA was tested by utilizing the following bacterial or viral strains. Positive and negative stools were spiked with ≥1x10° organisms / ml and tested by Premier Platinum HpSA. H. pylori gave a positive result when tested. All organisms were found to be negative when spiked into the negative stool. In addition, they did not interfere with the positive specimen:

Microorganism or virus (# strains tested)

| Adenovirus Type II (1) | Rotavirus (1) |
|-----------------------------|------------------------------------|
| Campylobacter coli (1) | Mycobacterium smegmatis (1) |
| Campylobacter fetus (1) | Nocardia asteroides (1) |
| Campylobacter jejuni (1) | Proteus vulgaris (1) |
| Campylobacter lari (1) | Salmonella (Group B) (1) |
| Candida albicans (1) | Salmonella dublin (1) |
| Citrobacter freundii (1) | Salmonella hilversum (Group N) (1) |
| Clostridium difficile (2) | Salmonella minnesota (1) |
| Clostridium perfringens (2) | Salmonella typhimurium (1) |
| Enterococcus faecalis (1) | Serratia liquefaciens (1) |
| Enterobacter cloacae (1) | Shigella boydii (1) |
| Escherichia coli (2) | Shigella dysenteriae (1) |
| Escherichia fergusonii (1) | Shigella flexneri (1) |

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- Response Items, Round 2: K980076 Premier Platinum HpSA
- Escherichia hermanii (1) Helicobacter cinaedi (1) Helicobacter mustelae (1) Klebsiella pneumoniae (1) Providencia stuartii (1) Pseudomonas aeruginosa (1) Pseudomonas fluorescens (2)

Interfering Substances: None

- Shigella sonnei (1) Staphylococcus aureus (1) Staphylococcus aureus (Cowan I) (1) Staphylococcus epidermidis (1) Streptococcus agalactiae (1) Steptococcus faecalis (1) Yersinia enterocolitica (2)

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Image /page/7/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo is a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized image of a caduceus, a symbol often associated with healthcare and medicine.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

MAY 1 2 1998

Dr. Allen D. Nickol Meridian Diagnostics, Inc. Director, Scient. & Req. Affairs 3471 River Hills Drive Cincinnati, Ohio 45244

K980076 Re: Trade Name: Premier Platinum HpSA Requlatory Class: I Product Code: LYR Dated: April 8, 1998 Received: April 9, 1998

Dear Dr. Nickol:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to 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). 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, listing of devices, good manufacturing practice, labeling, and prohibitions aqainst misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (Premarket Approval), it may be subject to such additional controls. Existing major requlations affecting your device can be found in the Code of Federal Requlations, Title 21, Parts 800 to 895. ಡ substantially equivalent determination assumes compliance with the current Good Manufacturing Practice requirement, as set forth in the Quality System Requlation (QS) for Medical General regulation (21 CFR Part 820) and that, Devices: through periodic (QS) inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory In addition, FDA may publish further announcements actien. concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531

through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or requlations.

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#### Page 2

Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at [phone].

This letter will allow you to begin marketing your device as described in your 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 vour device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at [phone]. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number [phone] or at [phone], or at its internet address "http://www.fda.gov/cdrh/dsmamain.html".

Sincerely yours,

Steven Gutman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

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Response Items: K980076 Premier Platinum HpSA

# Indications For Use Statement

510(k) Number (if known): K980076

Device Name: Premier HpSA

Indications For Use:

The Premier Platinum HpSA enzyme immunoassay (EIA) is an in vitro qualitative procedure for the detection of Helicobacter pylori antigens in human stool. Test results are intended to aid in the diagnosis of H. pylori infection in adult symptomatic patients.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Woody Dubois

ision of Clinical Laboratory Devi 510(k) Number.

Prescription Jse X (Per 21 CFR 801.109)

OR

Over-The-Counter Use (Optional Format 1-2-96)

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