The Binax NOW® Legionella Urinary Antigen Test is an in vitro rapid immunochromatographic assay for the qualitative detection of Legionella serogroup 1 antigen (L. pneumophila serogroup 1 antigen) in urine specimens from patients with symptoms of pneumonia. It is intended to aid in the presumptive diagnosis of Legionella infection ("Legionnaires" Disease) caused by L. pneumophila serogroup 1 in conjunction with culture and other methods.

Device Description

The Binax NOW® Legionella Urinary Antigen Test is an immunochromatographic membrane assay to detect Legionella pneumophila serogroup 1 antigen in human urine. A test strip, containing gold-conjugated and immobilized anti-Legionella pneumophila serogroup 1 antibodies, and a swab well are mounted on opposite sides of a cardboard, book-shaped hinged test device. A Dacron swab is dipped into the urine to be tested and then inserted into the swab well. A single reagent is added to the swab well from a dropper bottle before closing the test device. Legionella urinary antigen captured by immobilized anti-Legionella pneumophila antibody reacts to bind anti-Legionella pneumophila conjugated antibody, forming the Sample Line. Immobilized control antibody captures anti-species conjugate, forming the Control Line. There are no transferring steps, the sample is contained, and results are available in 15 minutes.

AI/ML Overview

This document describes the Binax NOW® Legionella Urinary Antigen Test, an immunochromatographic assay for detecting Legionella pneumophila serogroup 1 antigen in urine specimens. The 510(k) submission (K070522) aimed to demonstrate substantial equivalence to the unmodified Binax NOW® Legionella Urinary Antigen Test (K982238) after modifications to the device.

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria Category	Specific Criteria	Reported Device Performance	Study Type
Method Comparison	100% agreement between modified and unmodified device for negative and positive samples.	100% agreement between the modified and unmodified devices for 70 negative urine samples and 15 positive urine samples.	Method Comparison
Cross-Reactivity	No positive results with clinically relevant concentrations of common pneumonia-associated organisms and urogenital tract flora.	None of the 11 organisms tested (at 1x10^6 to 2x10^3 concentrations) tested positive on the modified device.	Cross-Reactivity Testing
Loss of Signal (LOS)	The same dilution of positive urine specimen should provide loss of signal on both the unmodified and modified devices.	In all three studies, the same dilution of positive urine provided loss of signal on both the unmodified and modified devices.	Loss of Signal (LOS) Testing
Stability	Not explicitly stated in terms of acceptance criteria, but crucial for product efficacy.	Stability studies of the modified test are currently ongoing.	Stability Studies

2. Sample Sizes and Data Provenance

Test Set (Method Comparison):
- Negative Samples: 70 urine samples
- Positive Samples: 15 known positive urine specimens
- Data Provenance: The document states that the negative urine samples were "collected from presumed healthy individuals." The provenance of the positive samples is not explicitly detailed but they are described as "known positive urine specimens." It is retrospective data as it describes samples that were already collected and classified. The country of origin is not specified.
Test Set (Cross-Reactivity):
- Number of Organisms Tested: 11
- Concentrations: Ranged from 1 x 10^6 to 2 x 10^3 (depending on the organism).
- Data Provenance: Whole organism cross-reactivity testing was performed. The organisms were grown in culture. Details on the origin of the cultures or their geographical provenance are not provided.
Test Set (Loss of Signal):
- Positive Urine Specimen: 1
- Lots Tested: 3 separate lots of the modified device.
- Data Provenance: Serial two-fold dilutions of a known positive urine specimen. Details on the origin of the specimen are not provided.

3. Number of Experts and Qualifications for Ground Truth

The document does not mention the use of experts to establish ground truth for the test sets. For the method comparison study, "known positive urine specimens" and "presumed healthy individuals" were used, implying prior methods established positivity and negativity. For cross-reactivity, organisms were grown in culture, indicating laboratory-derived ground truth. For loss of signal, a "known positive urine specimen" was used.

4. Adjudication Method

No adjudication method is described for the test sets. The studies rely on direct comparison to the predicate device or established laboratory standards.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No MRMC comparative effectiveness study was mentioned or performed. This device is an in vitro diagnostic (IVD) test, not an imaging device or an AI application designed to assist human readers in interpretation. Therefore, the concept of human readers improving with AI vs without AI assistance is not applicable here.

6. Standalone Performance

Yes, a standalone performance assessment was conducted for the modified device by comparing its results directly with the unmodified predicate device, and by testing its performance in cross-reactivity and loss-of-signal experiments. The device itself generates a qualitative result (positive/negative) without human interpretation in the loop to determine the primary outcome of the test.

7. Type of Ground Truth Used

The ground truth used appears to be a combination of:

Predicate Device Comparison: For the method comparison, the results of the unmodified predicate device served as the established "truth" for agreement.
Pre-classified Samples: "Known positive urine specimens" and urine from "presumed healthy individuals" imply prior diagnostic classification or health status determining the ground truth for these samples.
Laboratory-derived Standards: For cross-reactivity, the presence or absence of specific cultured organisms at known concentrations served as the ground truth. For loss of signal, the serial dilution of a known positive specimen was used.

8. Sample Size for the Training Set

No training set is mentioned in the provided text. This device is a rapid immunochromatographic assay, not an algorithm that requires a training set in the conventional sense of machine learning. The "training" in this context would refer to the development and optimization of the assay components (antibodies, membrane, etc.) rather than a data-driven model.

9. How the Ground Truth for the Training Set Was Established

As no training set is described or applicable in the context of this type of device, the method for establishing ground truth for a training set is not provided.

Summary

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510(k) Summary

This 510(k) summary of safety and effectiveness information is being submitted in accordance with the requirements of SMDA and 21 CFR 807.92.

SUBMITTER

Binax, Inc. d/b/a Inverness Medical Professional Diagnostics 10 Southgate Road Scarborough, Maine 04074

MAR 1 5 2007

CONTACT PERSON

Karen Mortimer (207) 730-5705 (Office) (207) 730-5710 (Fax) Karen.mortimer@invmed.com

ALTERNATE CONTACT

Pamela Angell (207) 730-5738 (Office) (207) 730-5710 (Fax) Pam.angell@invmed.com

DATE PREPARED

February 13, 2007

TRADE NAME

Binax NOW® Legionella Urinary Antigen Test

COMMON NAME

Legionella ICT

CLASSIFICATION NAME

Haemophilus spp. Serological reagents (per 21 CFR 866.3300)

PREDICATE DEVICE

Binax NOW® Legionella Urinary Antigen Test (unmodified) 510 (k) number K982238

DEVICE DESCRIPTION

The Binax NOW® Legionella Urinary Antigen Test is an immunochromatographic membrane assay to detect Legionella pneumophila serogroup 1 antigen in human urine. A test strip, containing gold-conjugated and immobilized anti-Legionella pneumophila serogroup 1 antibodies, and a swab well are mounted on opposite sides of a cardboard, book-shaped hinged test device. A Dacron swab is dipped into the urine to be tested and then inserted into the swab well. A single reagent is added to the swab well from a dropper bottle before closing Legionella urinary antigen captured by immobilized anti-Legionella the test device. pneumophila antibody reacts to bind anti-Legionella pneumophila conjugated antibody, forming the Sample Line. Immobilized control antibody captures anti-species conjugate, forming the Control Line. There are no transferring steps, the sample is contained, and results are available in 15 minutes.

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nary (contir

INTENDED USE

TECHNOLOGICAL CHARACTERISTICS

The Binax NOW® Legionella Urinary Antigen Test uses lateral flow immunochromatographic technology. The test is a rapid immunoassay that employs specific antibodies immobilized onto a solid phase to capture and visualize Legionella pneumophila serogroup 1 antigen. (The modified and cleared Binax NOW® Legionella Urinary Antigen Tests share the same technological characteristics and antigen detection reagents. Assay procedure, intended use and product claims are unchanged for the modified device.)

PERFORMANCE SUMMARY

Stability, Method Comparison, Cross Reactivity and Loss of Signal testing were performed on the modified device to ensure its equivalence to the unmodified device. The changes to the NOW® Legionella Urinary Antigen Test have not affected its safety or effectiveness as detailed below:

STABILITY STUDIES:

Stability studies of the modified test are currently ongoing,

METHOD COMPARISON:

Seventy (70) urine samples, collected from presumed healthy individuals, were tested on the modified and cleared devices yielding negative results and demonstrating 100% agreement between the two devices. Fifteen (15) known positive urine specimens were tested on the modified and unmodified devices yielding positive results and again demonstrating 100% agreement.

CROSS-REACTIVITY TESTING:

In the original 510(K) submission, cross reactivity testing was performed using urines from patients diagnosed with other (non-Legionella) bacterial or fungal pneumonia or urinary tract infections. In lieu of this, whole organism cross-reactivity testing was performed to compare the modified and unmodified devices.

Given that modifications to the device do NOT impact the detection portion of the assay, a limited cross-reactant panel of 11 organisms was tested. The panel included organisms associated with pneumonia as well as those likely to be found in the urogenital tract as normal flora or as the result of a urinary tract infection. None of the organisms, grown in culture and tested at clinically relevant concentrations (depending on the organism 1 x 10° to 2 x 103), tested positive on the modified test.

LOSS OF SIGNAL (LOS) TESTING:

Serial two-fold dilutions of a known positive urine specimen were run on the unmodified and modified devices. Three (3) separate lots of the modified device were tested against

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510 (k) Summary (continued) 11:40:00

unmodified devices. In all three studies, the same dilution of the positive urine provided loss of signal on both the unmodified and modified devices.

lifell and amo 2116/07 ______________________________________________________________________________________________________________________________________________________________________________ Signed

Pamela Angell, Director, Worldwide Clinical Affairs Binax, Inc. d/b/a Inverness Medical Professional Diagnostics

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo features a stylized eagle with its wings spread, symbolizing protection and service. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES · USA" is arranged in a circular fashion around the eagle, indicating the department's name and national affiliation. The logo is presented in black and white, giving it a formal and official appearance.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Karen Mortimer Clinical Affairs Specialist Binax, Inc. Inverness Medical Professional Diagnostics 10 Southgate Road Scarborough, ME 04074

MAR 1 5 2007

Re: K070522

Trade/Device Name: BinaxNOW® Legionella Urinary Antigen Test Regulation Number: 21 CFR 866.3300 Regulation Name: Haemophilus spp. serological reagents Regulatory Class: Class II Product Code: MJH Dated: February 14, 2007 Received: February 23, 2007

Dear Ms. Mortimer:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and 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) that do not require approval of a premarket approval application (PMA). 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 (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240)276-0450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Sally, attorn

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 STATEMENT

510(k) Number (if known): _ Kn 705 32

Device Name: BinaxNOw® Legionella Urinary Antigen Test

Indications For Use:

The Binax NOW® Legionella Urinary Antigen Test is an in vitro rapid immunochromatographic assay for the qualitative detection of Legionella serogroup 1 antigen (L. pneumophila serogroup 1 antigen) in urine specimens from patients with symptoms of pneumonia. It is intended to aid in the presumptive diagnosis of Legionella infection (Legionnaires' disease) caused by L. pneumophila serogroup 1 in conjunction with culture and other methods.

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

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

Freddie Lu-Poole

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

070522

Regulation Number and Section

§ 866.3300

Haemophilus spp. serological reagents.(a)
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 identifyHaemophilus 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 genusHaemophilus and provides epidemiological information on diseases cause by these microorganisms. Diseases most often caused byHaemophilus spp. include pneumonia, pharyngitis, sinusitis, vaginitis, chancroid venereal disease, and a contagious form of conjunctivitis (inflammation of eyelid membranes).(b)
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.