BARTELS LEGIONELLA URINARY ANTIGEN ELISA TEST

K991074 · Intracel Corp. · MJH · Dec 21, 1999 · Microbiology

Device Facts

• Record ID: K991074
• Device Name: BARTELS LEGIONELLA URINARY ANTIGEN ELISA TEST
• Applicant: Intracel Corp.
• Product Code: MJH · Microbiology
• Decision Date: Dec 21, 1999
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3300
• Device Class: Class 2

Intended Use

Bartels Legionella Urinary Antigen ELISA Test is intended as an adjunct to culture for the presumptive diagnosis of past or current Legionnaires' Disease by qualitative detection of Legionella pneumophila Serogroup 1 antigen in human urine.

Device Story

Device is an enzyme-linked immunosorbent assay (ELISA) for qualitative detection of Legionella pneumophila Serogroup 1 antigen in human urine. Input: 100 µL urine specimen added to microelisa stripwells pre-coated with rabbit anti-Legionella capture antibodies. Process: Addition of HRP-conjugated rabbit antibodies; incubation; wash cycles; addition of TMB/H2O2 substrate; addition of phosphoric acid stop solution. Output: Colorimetric signal measured at 450 nm via plate reader or compared against visual interpretation card. Used in clinical laboratories; operated by laboratory personnel. Results aid clinicians in presumptive diagnosis of Legionnaires' Disease as an adjunct to culture, facilitating timely patient management.

Clinical Evidence

Clinical study of 274 urine specimens (94 culture-positive for L. pneumophila, 150 non-Legionella, 30 healthy). Compared to culture gold standard, device showed 94.7% sensitivity, 91.1% specificity, and 92.3% accuracy. Comparison of automated plate reader vs. visual interpretation card showed 92.6% sensitivity and 93.9% specificity for visual method.

Technological Characteristics

Antigen capture (sandwich) ELISA. Components: microelisa stripwells coated with purified rabbit anti-Legionella pneumophila Serogroup 1 IgG; HRP-conjugated rabbit anti-Legionella IgG; TMB/H2O2 substrate; phosphoric acid stop solution. Manual or automated wash procedure. Readout via 450 nm microelisa plate reader or visual interpretation card. Storage 2-8°C.

Indications for Use

Indicated for individuals suspected of acute infection by Legionella pneumophila Serotype 1 for the presumptive diagnosis of past or current Legionnaires' Disease via qualitative detection of antigen in human urine.

Regulatory Classification

Identification

Haemophilus spp. serological reagents are devices that consist of antigens and antisera, including antisera conjugated with a fluorescent dye, that are used in serological tests to identify Haemophilus spp. directly from clinical specimens or tissue culture isolates derived from clinical specimens. The identification aids in the diagnosis of diseases caused by bacteria belonging to the genus Haemophilus and provides epidemiological information on diseases cause by these microorganisms. Diseases most often caused by Haemophilus spp. include pneumonia, pharyngitis, sinusitis, vaginitis, chancroid venereal disease, and a contagious form of conjunctivitis (inflammation of eyelid membranes).

Special Controls

*Classification.* Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 866.9.

Predicate Devices

• Binax Legionella Urinary Antigen EIA

Submission Summary (Full Text)

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DEC 2 1 1999

K991074

000018

## 510(k) SUMMARY

### A. Name of Device and Classification

Bartels Legionella Urinary Antigen ELISA Test Trade Name:

Bartels Legionella Urinary Antigen ELISA Test is an enzyme-Classification: linked immunoassay that detects Legionella pneumophila Serogroup 1 antigen in human urine. This test has been classified as a Class II (performance standards) device, product code MJH (21 CFR 866.3300).

#### B. Legally Marketed Device

Bartels Legionella Urinary Antigen ELISA Test claims substantial equivalence to the Binax Legionella Urinary Antigen EIA.

#### C. Device Description

Bartels Legionella Urinary Antigen ELISA Test is an enzyme-linked immunoassay intended for the qualitative detection of Legionella pneumophila Serogroup 1 antigen in human urine. The kit consists of microelisa stripwells with lid, positive and negative control reagents, conjugate, wash concentrate, colorimetric substrate (2 components) and stop solution. Sufficient materials are provided to perform 96 analyses.

The microelisa wells have been pre-coated with purified rabbit antibodies to Legionella pneumophila Serotype 1 (capture antibody). An undiluted urine specimen (100 µL), or positive or negative controls (100 µL each) are each placed in a single microelisa well followed by the addition of 50 uL of Conjugate (horseradish peroxidase-conjugated rabbit antibodies to L. pneumophila). The loaded microelisa plate is then covered with the lid and incubated for 48 to 52 minutes at 34-37°C followed by 4 cycles of wash/aspiration using diluted Wash Solution (manual or automated wash procedure). Colorimetric substrate (tetramethyl benzidine/H2O2 100 µL/well) is then added and incubated for 10 to 12 minutes at 34-37℃ followed by the addition of Stop Solution (1M Phosphoric acid, 100 uL/well). The stopped plate is then read on a microelisa plate reader at 450 nm against an air blank. For a test to be considered valid, the Negative Control must have an optical density (OD) value of less than 0.100 and the Positive Control must be greater than the Positive Cutoff (pco). The pco is equal to 4X the O.D. value of the Negative Control value. Any specimen with an O.D. value ≥ the pco is considered positive. Any specimen with an O.D. value < the pco is considered negative. Alternatively, the results can be visually read. For this purpose, a visual interpretation card, and written instructions, are provided in the kit for interpretation of results. Any well that produces definite yellow color is considered to be positive.

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The following components are provided in each Bartels LUA ELISA kit:

- Micro Wells, 96 break-away coated wells with purified rabbit anti-Legionella 1. pneumophila Serogroup 1, IgG fraction. Ready to use. Store at 2-8°C.
- Conjugate, 6.5 mL bottle of purified rabbit anti-Legionella pneumophila 2. Serogroup 1 IgG conjugated to horseradish peroxidase (HRP) in a buffer with protein stabilizer in a red tracking dye. Ready to use. Store at 2-8°C.
- 3. Wash Concentrate (20X), 100 mL bottle of buffered saline with detergent and thimerosal. 20X concentrate; dilute 1:20 with distilled or deionized water before use. Store at 2-30°C.
- Substrate A, 12mL bottle of tetramethyl benzidine (TMB). Ready to use. 4. Store at 2-8°C.
- ર . Substrate B, 12mL bottle of hydrogen peroxide (H2O2). Ready to use. Store at 2-8°C.
- Stop Solution, 12mL bottle of 1M phosphoric acid. Ready to use. Store at 2-6. 30°C.
- Positive Control. 1.5mL bottle of human urine containing Legionella 7. pneumophila serogroup 1 antigen and preservative. Ready to use. Store at 2-8°C.
- 8. Negative Control, 1.5mL bottle of normal human urine and preservative. Ready to use. Store at 2-8°C.
- இ Visual Interpretation Card - Visual interpretation card displaying 5 levels of vellow color intensity.
- 10. Package Insert, Detailed description of test procedure and interpretation of results.

#### D. Intended Use

Bartels Legionella Urinary Antigen ELISA Test is intended as an adjunct to culture for the presumptive diagnosis of past or current Legionnaires' Disease by qualitative detection of Legionella pneumophila Serogroup 1 antigen in human urine.

#### E. Comparison with the Predicate Device

Bartels Legionella Urinary Antigen ELISA Test, bv the antigen capture sandwich ELISA technique described in this application, is substantially equivalent to the currently marketed Binax Legionella Urinary Antigen EIA which has been cleared by FDA through 510(k) premarket notification. Both kits share common intended use statements, target populations, design/format. kit materials, performance characteristics, absence of risk to patients, specimen type and analytes. The following table (Table 1) summarizes the similarities

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| Table 1: Comparison of Devices | | |
|-----------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Product Name | Bartels Legionella Urinary Antigen<br>ELISA Test | Binax Legionella Urinary Antigen<br>EIA |
| Intended Use<br>Statement | "Bartels Legionella Urinary Antigen<br>ELISA Test is intended as an adjunct<br>to culture for the presumptive<br>diagnosis of past or current<br>Legionnaires' Disease by qualitative<br>detection of Legionella pneumophila<br>Serogroup 1 antigen in human urine." | "This kit is an enzyme immunoassay<br>(EIA) based system intended for in<br>vitro diagnostic use to qualitatively<br>detect the presence of Legionella<br>pneumophila Serogroup 1 antigen (L.<br>pneumophila Serogroup 1 antigen) in<br>human urine as an adjunct to culture<br>for the presumptive diagnosis of past<br>or current Legionnaires' Disease." |
| Target Population | Individuals suspected of acute<br>infection by Legionella pneumophila<br>Serotype 1. | Individuals suspected of acute<br>infection by Legionella pneumophila<br>Serotype 1. |
| Design/format | Antigen capture (sandwich) enzyme<br>immunoassay. | Antigen capture (sandwich) enzyme<br>immunoassay. |
| Materials | Microelisa stripwells coated with<br>rabbit polyclonal antibodies to L.<br>pneumophila Serotype 1, HRP<br>polyclonal antibodies to L.<br>pneumophila Serotype 1, positive and<br>negative controls, wash concentrate,<br>tetramethyl benzidine/H2O2 (TMB)<br>colorimetric substrate, stop solution,<br>visual interpretation card, package<br>insert. | Microelisa stripwells coated with<br>rabbit polyclonal antibodies to L.<br>pneumophila Serotype 1, HRP<br>polyclonal antibodies to L.<br>pneumophila Serotype 1, positive and<br>negative controls, wash concentrate,<br>tetramethyl benzidine/H2O2 (TMB)<br>colorimetric substrate, stop solution,<br>package insert. |
| Performance<br>Characteristics<br>(Described in<br>Section 10). | Using culture method as "gold<br>standard":<br>Sensitivity: 94.7%<br>Specificity: 91.1%<br>Accuracy: 92.3% | Using culture method as "gold<br>standard":<br>Sensitivity: 87.2%<br>Specificity: 86.7%<br>Accuracy: 86.9% |
| Risk to patient | No unique issues of safety or<br>effectiveness. | No unique issues of safety or<br>effectiveness. |
| Specimen Type | Voided urine. | Voided urine. |
| Analyte | Legionella pneumophila Serotype 1<br>soluble urinary antigen | Legionella pneumophila Serotype 1<br>soluble urinary antigen |

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of Bartels Legionella Urinary Antigen ELISA Test and Binax Legionella Urinary Antigen EIA:

#### Performance Data F.

A clinical study was performed on 274 clinically well-defined urine specimens at a major infectious disease reference laboratory. The study consisted of: a) 94 urine specimens from patients whose respiratory specimens were culture-positive for Legionella pneumophila Serogroup 1; b) 150 urine specimens from who did not have a diagnosis of Legionella pneumophila; and c) 30 urine specimens from normal healthy volunteers. The Bartels Legionella Urinary Antigen ELISA Test had a sensitivity of 94.7%, specificity of 91.1% and accuracy of 92.3%. Substantial equivalence was established between the Bartels LUA and the predicate device.

In this study, a comparison was also made for the Bartels LUA ELISA Test between results obtained with the automated plate reader vs. the use of a visual interpretation card. The sensitivity of the visual interpretation was 92.6%, specificity was 93.9% and accuracy was 93.4%.

#### G. Conclusion

The Bartels Legionella Urinary Antigen ELISA Test is substantially equivalent to the Binax Legionella Urinary Antigen EIA. Furthermore, with the Bartels LUA ELISA Test, there is equivalence between reading the results with an automated plate reader and performing a visual interpretation.

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Confidential

## Name of Submitter:

INTRACEL Corporation 1330 Piccard Dr. Rockville, MD 20850 Phone: [phone] Fax:

Name of Contact Person:

Sheryl Ruppel Regulatory Affairs Manager INTRACEL Corporation 1330 Piccard Dr. Rockville, MD 20850 Phone: [phone] Ext. 1089 Fax:

March 30, 1999 Date Prepared:

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DEC 2 1 1999

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Sheryl Ruppel Regulatory Affairs Manager INTRACEL Corporation 1330 Piccard Drive Rockville, Maryland 20850

Re: K991074 Trade Name: Bartels Legionella Urinary Antigen ELISA Test Regulatory Class: II Product Code: MJH Dated: November 19, 1999 Received: November 19, 1999

Dear Ms. Ruppel:

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 legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act). 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 against 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 regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, 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 action. In addition, FDA may publish further announcements 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 regulations.

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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 Butman

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

Enclosure

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Page_1 of_1

# 510(k) Number (if known): K991074

Bartels Legionella Urinary Device Name:

Antigen ELISA Test

## Indications For Use:

Bartels Legionella Urinary Antigen ELISA Test is intended as an adjunct to culture for the presumptive diagnosis of past or current Legionnaires' Disease by qualitative detection of Legionella pneumophila serogroup l antigen in human urine.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Woody Dubois

(Division Sign Off)
Division of Clinical Laboratory Devices
510(k) Number K991074

Prescription Use
(Per 21 CFR 801.109)

OR

Over-The-Counter Use__________________________________________________________________________________________________________________________________________________________

(Optional Format 1-2-96)