(20 days)
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.
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.
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
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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.
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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.
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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.
§ 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.