The Binax NOW Streptococcus pneumoniae Urinary Antigen Test is a rapid immunochromatographic assay for the detection of S. pneumoniae antigen in urine specimens from patients with symptoms of pneumonia. It is intended to aid in the presumptive diagnosis of pneumococcal pneumonia in conjunction with culture and other methods.

Device Description

The Binax Now Streptococcus pneumoniae Antigen Test is a urinary immunochromatographic membrane assay used to detect Streptococcus pneumoniae (S. pneumoniae) antigen in human urine. A test strip, containing gold-conjugated and immobilized anti-S. pneumoniae antibodies, and a swab well are mounted on opposite sides of a cardboard, book-shaped hinged test device. A 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. Pneumococcal antigen present in the urine sample reacts to bind anti-S. pneumoniae antibody conjugated to gold. The resulting antigen-conjugate complexes are captured by immobilized anti-S. pneumoniae antibody, forming the Sample Line. Immobilized goat anti-rabbit IgG captures excess visualizing conjugate, forming the Control Line.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study details for the Binax NOW® Streptococcus pneumoniae Urinary Antigen Test, based on the provided 510(k) notification:

Acceptance Criteria and Reported Device Performance

The acceptance criteria for diagnostic devices like this are typically infered from the demonstrated performance that the FDA deems sufficient for market clearance, often in comparison to a predicate device. For this submission, the performance results are presented as the device's demonstrated capabilities.

Table 1: Acceptance Criteria and Reported Device Performance

Metric	Acceptance Criteria (Inferred from Study)	Reported Device Performance (Retrospective Study)	Reported Device Performance (Prospective Multi-center Study)
Clinical Sensitivity	(Sufficiently high to aid in diagnosis, comparable to predicate or clinical need)	86% (70.9% - 93.9% CI)	90% (74.6% - 96.4% CI)
Clinical Specificity	(Sufficiently high to avoid false positives, comparable to predicate or clinical need)	94% (90.9% - 96.0% CI)	75% (69.3% - 81.5% CI)
Overall Accuracy	(Sufficiently high for clinical utility)	93% (89.9% - 95.1% CI)	77% (71.9% - 83.0% CI)
Analytic Sensitivity	Detects common pathogenic serotypes	100% detection of 44 isolates representing 23 serotypes at 10^5 organisms/mL	Not separately reported for this criterion, but intrinsic to clinical performance
Analytic Specificity	No cross-reactivity with common related organisms/flora	No cross-reactivity with 143 of 144 organisms; 1 recognized cross-reactant (Streptococcus mitis)	Not separately reported for this criterion, but intrinsic to clinical performance
Interfering Substances	No interference from common urine components	No cross-reactivity with 19 common interfering substances (blood, cells, protein, glucose, turbidity)	Not separately reported, but included in overall performance
Reproducibility	Consistent results across different sites/operators	99.4% agreement among 3 sites with negative, low positive, moderate positive, and high positive controls	Not separately reported, but assessed in reproducibility study
Quality Control	Procedural controls indicate test failure	Procedural control indicated failures when devices were intentionally made defective	Not separately reported, but assessed in QC study
Pneumococcal Vaccine Impact	Acceptable impact of vaccine on test results	13% tested positive within 30 hours of vaccination, then negative by 48 hours. Product labeling will warn not to test within 48 hours of vaccination.	Not separately reported, but assessed in vaccine study

Study Details

2. Sample Sizes and Data Provenance for Test Set:

Retrospective Study:
- Total Samples: 373 urine specimens
- Positive Cases: 35 urine specimens from blood culture positive pneumococcal pneumonia patients.
- Negative Cases: 338 urine specimens from presumed S. pneumoniae negative patients (28 from bacteremic patients, 4 from empyema, 53 from pneumonia, 153 from UTIs, 100 from no known infection).
- Provenance: Not explicitly stated, but likely from a diverse patient population given the varied sources of negative samples. Described as "freshly collected and characterized frozen urine specimens," suggesting a mix of past and potentially more recent collections. This indicates a retrospective study.
Multi-center Prospective Study:
- Total Samples: 215 urine specimens
- Patients: Hospitalized or out-patients presenting with lower respiratory symptoms or sepsis, suspected of pneumococcal pneumonia.
- Provenance: "separate multi-center prospective study." This indicates a prospective study from multiple clinical sites. Country of origin not specified.
Analytic Sensitivity: 44 isolates representing 23 Streptococcus pneumoniae serotypes.
Analytic Specificity (Cross-Reactivity): 144 potential cross-reactants (organisms associated with pneumonia and urogenital tract flora).
Interfering Substances: 19 urine specimens with potentially interfering substances (e.g., blood, WBC, protein, glucose, turbidity).
Pneumococcal Vaccine: Number of study participants not explicitly stated, but implies a group received the vaccine.
Reproducibility: A panel of coded specimens (negative, low positive, moderate positive, high positive controls) used at 3 separate sites. Number of specimens in the panel is not specified.
Quality Control: 20 devices with induced defects.

3. Number of Experts and Qualifications for Ground Truth:

The document does not explicitly mention the use of experts to establish a "ground truth" through consensus or review for the clinical studies.
The ground truth for the clinical studies relies on blood culture results (see point 7).
For analytic sensitivity, the "known Streptococcus pneumoniae serotypes" imply a microbiological expert's identification and characterization.
For analytic specificity, the "known cross-reactants grown in culture" implies microbiological identification.

4. Adjudication Method for Test Set:

None explicitly stated for the clinical performance studies.
The ground truth for clinical cases (blood culture positive/negative) is an objective laboratory result, not typically subject to adjudication by multiple human readers for diagnostic accuracy.

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

No, a MRMC comparative effectiveness study was not conducted.
The study focuses on the standalone performance of the device against an objective standard (blood culture), not on how human readers' performance improves with or without the device's assistance.

6. Standalone Performance Study:

Yes, a standalone (algorithm only without human-in-the-loop performance) study was performed. The entire clinical performance section (Clinical Sensitivity and Specificity) describes the performance of the Binax NOW® test independently from human interpretation beyond reading the visual result.

7. Type of Ground Truth Used:

Blood Culture: For both the retrospective and multi-center prospective clinical studies, the primary ground truth used to determine the presence or absence of S. pneumoniae infection was blood culture results.
Microbiological Culture/Identification: For analytic sensitivity, the ground truth was the presence of known S. pneumoniae serotypes at a specified concentration via culture. For analytic specificity, it was the identification of specific microbial species/isolates.
Defined Chemical/Cellular Composition: For interfering substances, the ground truth was the known presence of elevated levels of specific substances (e.g., blood, WBC, protein, glucose, turbidity).

8. Sample Size for the Training Set:

The document does not specify a training set size. This is common for diagnostic device submissions where the device's design is often based on fundamental scientific principles (e.g., antibody-antigen binding) and optimized through iterative development rather than a distinct machine learning "training" phase with a large, labeled dataset in the way an AI algorithm might have. The studies described are performance validation studies.

9. How Ground Truth for Training Set Was Established:

As no explicit training set is identified, the method for establishing its ground truth is not applicable/not documented in this submission. The "performance verification" used "freshly collected and characterized frozen urine specimens," which were then used in the retrospective study, suggesting these types of samples were used in the development and initial validation process without being formally labeled as a "training set." The development of the assay itself would have involved establishing the optimal antibody pair and concentrations through laboratory testing against known positive and negative samples.

Summary

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K991726
5/11/99 Revision

Dinax, Inc. Binax NOW® Streptococcus pneumoniae Urinary Antigen Test 510(k) Notification

510 (k) SUMMARY OF SAFETY AND EFFECTIVENESS )AUG 27 1999 Binax NOW Streptococcus pneumoniae Urinary Antigen Test

This 510(k) summary of safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

Submitter: Binax, Inc. 217 Read Street Portland, Maine 04103

Attention: Pamela S. Angell (207) 772-3988 (Office) (207) 871-5751 (FAX) pangell@binax.com (email)

Binax NOW" Streptococcus pneumoniae Urinary Trade Name: Antigen Test

Strep pneumo ICT, Binax NOW® Strep pneumo Common Name : test

Classification Name: Streptococcus spp. serological reagents (per 21 CFR 8660.3740)
Wellcogen Bacterial Antigen Kit, 510(k) Predicate Device: number K854852
Binax Now Streptococcus pneumoniae Device Description: The Antigen Test is ਤੇ ਸ Ilrinary immunochromatographic membrane assay used to pneumoniae (S. Streptococcus detect pneumoniae) antigen in human urine. A test containing gold-conjugated and strip, immobilized anti-S. pneumoniae antibodies, and a swab well are mounted on opposite sides of a cardboard, book-shaped hinged test device. A 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 device. Pneumococcal the test closing antigen present in the urine sample reacts bind anti-S. pneumoniae conjugated to antibody. The resulting antigen-conjugate complexes are captured by immobilized anti-S. pneumoniae antibody, forming the Sample Line. Immobilized goat anti-rabbit IgG captures excess visualizing conjugate, forming the Control Line.

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SUMMARY OF SAFETY AND EFFECTIVENESS 510 (k) (Continued)

There are no transferring steps, the sample contained, and results are available is within 15 minutes.

NOW® Streptococcus pneumoniae Binax Intended Use: The Urinary Antigen Test is an in vitro rapid immunochromatographic assay for the detection of S. pneumoniae antigen in urine specimens from patients with symptoms of pneumonia. It is intended to aid in the presumptive diagnosis of pneumococcal pneumonia in conjunction with culture and other methods.

Both the Binax NOW® Streptococcus Technological pneumoniae Urinary Antigen and the Wellcogen Characteristics : Bacterial Antigen Tests are simple rapid tests with a visual result interpretation. Both use a solid phase coated with polyclonal antibody to detect S. pneumoniae antigen in human urine samples. However, the predicate device is a latex agglutination test employing antibody coated polystyrene beads that agglutinate in the presence of The Binax sufficient homologous antigen. Streptococcus pneumoniae Urinary NOW® Antigen Test is an immunochromatographic assay utilizing a colloidal gold conjugate and an antibody striped membrane to capture and visualize antigen.

Binax NOW® Streptococcus pneumoniae Performance Summary: The Urinary Antigen Test is substantially equivalent to the predicate device, the Wellcogen Bacterial Antigen Test (K854852), for the detection of S. pneumoniae urinary The performance of the Binax NOW antigen. Streptococcus pneumoniae Urinary Antigen Test was verified using freshly collected and characterized frozen urine specimens. PERFORMANCE attached to Refer CHARACTERISTICS .

Signed J. George Nitis Date 5/19/99.
J. Georges Nitis, Ph.D., MBA
Director, Regulatory Affairs

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Binax, Inc. Binax NOW® Streptococcus pneumoniae Urinary Antigen Test 510(k) Notification

510 (k) SUMMARY OF SAFETY AND EFFECTIVENESS (Continued)

PERFORMANCE CHARACTERISTICS BINAX NOW" STREPTOCOCCUS PNEUMONIAE URINARY ANTIGEN TEST

Analytic Sensitivity:

Twenty-three (23) of 83 known Streptococcus pneumoniae serotypes are responsible for at least 90% of serious pneumococcal infection worldwide. I Forty-four (44) isolates representing these 23 serotypes and one additional serotype were grown in culture and assayed in the Binax NOW test at a concentration of 10° organisms/mL. One hundred percent (100%) were positive, indicating that the Binax NOW test detects the most pathogenic S. pneumoniae serotypes.

Analytic Specificity (Cross-Reactivity) :

To demonstrate the immunologic specificity of the Binax NOW test, 144 potential cross-reactants were grown in culture and tested in the Binax NOW® test. The cross-reactant panel included organisms associated with pneumonia as well as those likely to be found in the urogenital tract as normal flora or as a result of urinary The Binax NOW test does not cross-react with 143 tract infection. of the 144 organisms when tested at concentrations of 10° to 10° The single positive organism, Streptococcus mitis, is an CFU/mL. expected cross-reactant as is shares the antigen against which the Binax NOW test is directed. Streptococcus mitis is associated with endocarditis, not pneumonia, and is not likely to appear with any frequency in the population intended to be tested with the NOW test.la

Clinical Sensitivity and Specificity:

The Binax NOW Streptococcus pneumoniae Urinary Antigen Test was evaluated in both prospective and retrospective clinical studies.

In the retrospective study, 35 urine specimens from blood culture positive pneumococcal pneumonia patients and 338 urine specimens from presumed S. pneumoniae negative patients were evaluated in the NOW test. Of the presumed negative urines, 28 were collected from bacteremic patients, 4 from patients with empyema, 53 from patients with pneumonia, 153 from patients with urinary tract infections, and 100 from patients with no known infection. Binax NOW test performance, calculated using standard methods, was 86% sensitivity, 94% specificity, and 93% overall accuracy. Ninetyfive percent (95%) confidence intervals are listed below.

1 Refer to Product Insert reference number 9.

la Howard, B.J., Clinical & Pathogenic Microbiology, 200 ed. 1994. Mosby-Year Book Inc., St. Louis, MO., pg 267.

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SUMMARY OF SAFETY AND EFFECTIVENESS 510 (k)

PERFORMANCE CHARACTERISTICS (Continued) BINAX NOW STREPTOCOCCUS PNEUMONIAE URINARY ANTIGEN TEST

		Blood Culture
		+	-
NOW®Result	+	30	21
	-	5	317
Sensitivity		= 86%	(70.9% - 93.9%)
Specificity		= 94%	(90.9% - 96.0%)
Accuracy		= 93%	(89.9% - 95.1%)

In a separate multi-center prospective study, 215 urine specimens
t and the colornitalized or out-patients presenting with lower In a separate multi-center prospective scady razont with lower
from either hospitalized or out-patients presenting with lower from either nospitalized respiratory symptoms or sepsis and result in the Now test. suspected of pneumococal pneumon was collected within 24 hours of
The confirmatory blood specimen was collected within 24 hours of Now test performance versus the conrinuation, and then cultured. standard methods, was 90% ne Sample ample and using re, calculated fusing Standard accuracy. Ninety 76% specificity, and 78% overall accuracy. blood sensitivity, sensitivity, 76% specificity, and 450-ar-listed below.
five percent (95%) confidence intervals are listed below.

		Blood Culture
		+	-
NOW®Result	+	28	45
	-	3	135
Sensitivity	=	90% (74.6% - 96.4%)
Specificity	=	75% (69.3% - 81.5%)
Accuracy	=	77% (71.9% - 83.0%)

Interfering Substances:

Interfering Substances: found not to cross-react with potentially Nineteen (19) urine The Binax Now test was reasons in urine.
interfering substances present of white blo interfering substances present in urne. Innovous of and blood specimens with elevated levels of urines with high turbidity, and cells, protein, and/or gilcose, 3 triles warameters were 5 urines normal with respect to each of act (20) specimens were the Binax NOW test. Twenty-eight (20) specimen with negative. The single invalid Cest, products by Self
elevated red blood cells, could not be interpreted due to the negative. elevated Ted brood Coller, extreme coloration of the test membrane.

Pneumococcal Vaccine:

ﻤﺴﺎﻫﻤﺎﺕ

Pheumococcal Vaccine on Binax NOW test performance impact of S. pheumoniae vaccine on blick home of the more of the the Lederle Pnu-Immune® was 23 before and after immunization with d atter immunization with the golive in the Binax NOW"
All study participants tested negative in the Binax positive vaccine. vaccine. All study participants cessed nogation of the tested positive
test before vaccination. Thirten percent (133) tested negative test before vaccination. Thirtcen possour in
within 30 hours of being vaccinated, but again tested negative

6 - 4

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Binax, Inc.
Binax Now® Streptococcus pneumoniae Urinary Antigen Test 10(k) Notification

510 (k) SUMMARY OF SAFETY AND EFFECTIVENESS

PERFORMANCE CHARACTERISTICS (Continued) BINAX NOW STREPTOCOCCUS PNEUMONIAE URINARY ANTIGEN TEST

within 48 hours of vaccination. Binax NGW test product labeling within 48 hours of Vaccination. " Binax Now " " " " " " " " " " " " " " " " " " false positive results in the Binax NOW® test in the 48 hours false positive results in the binnended that the Binax NOW" test following varchhatlon. Te is receiving the S. pneumoniae vaccine.

Reproducibility :

Reproductibility.
A blind study of the Binax NOW test was conducted at 3 separate A blind study of the Binax Row couraning negative, low sites using a panel of coded specialism positive urine controls.
positive, moderate positive and 2 different ave 99 4% of the positive, moderate posicive and ligh poent days. 99.4% of the Farcicipants porrolmed and correctly interpreted.

Quality Control:

The ability of the Binax NOW® Test procedural control to indicate test failure was evaluated when 3 operators each rain 200 kit test failure was evaluated which 5 openatib had been rendered controls in a panel of 20 oevices of defective and the defect itself were not apparent to the operator. Increase of the more in the itself were not apparent to the opensive, negative, negative, or invalid.

Preliminary Stability:

Preliminary Stability studies of the Binax NOW Streptococcus Preliminary Stability Studics of Chicals are ongoiny. Tost
pneumoniae Urinary Antigen Test and kit controls are ongoiny. Cleared ICT pheumoniae Urinary Ancigen Itso and Sinax 510 (k) cleared ICT
results are consistent with other is sticipated results are consistent with

6 - 5

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Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is a circular emblem with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES · USA" arranged around the top half of the circle. Inside the circle is a stylized image of an eagle with its wings spread.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

AUG 27 1999

Ms. Pamela S. Angell Program Manager Binax, Inc. 217 Read Street Portland, Maine 04103

Re: K991726

K991726
Trade Name: Binax Now® Streptococcus pneumoniae Urinary Antigen Test Regulatory Class: II Product Code: GTZ Dated: August 18, 1999 Received: August 23, 1999

Dear Ms. Angell:

We have reviewed your Section 510(k) notification of intent to market the device referenced We have reviewed your Section 510(x) notifically equivalent (for the indications for use above and we have determined the device is subscribes marketed in interstate commerce
stated in the enclosure) to legally marketed prodical of Desice Amendments, or to device stated in the enclosure) to legally marked predice in the Medice Amendments, or to devices that
prior to May 28, 1976, the enactment date of the Medical Food Drug, and prior to May 28, 1970, the enactinen date of the Federal Food, Drug, and have been reclassified in accordance with the provisions of as been to the general controls
Cosmetic Act (Act). You may, therefore, market the Action Actively requirements f Cosmetic Act (Act). You may, merciors, mance include requirements for annual provisions of the Act. "The general controls provisions of an and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III If your device is classified (see above) into cities in controls. Existing major regulations (Premarket Approval), it may be subject to sateral Regulations, Title 21, Parts 800 to 895.
affecting your device can be found in the Code of Federal Regulations Current Good affecting your device can be louid in the essumes compliance with the Current Good A substantially equivalent detemmination asset forth in the Quality System Regulation (OS) for
Manufacturing Practice requirements, as set forth in the Quality System Regula Manufacturing Practice requirements, as the rear 820) and that, through periodic QS
Medical Devices: General regulation (21 CFR Part & exchange with answers and Medical Devices: General regulation (2) CFR Part Party such assumptions. Failure to
inspections, the Food and Drug Administration (FDA) will sectify such assumptions, EDA inspections, the Food and Drug Aummistration in addition, FDA may publish
comply with the GMP regulation may result in regulation, Places note: this comply with the GMF Tegulation may result in the Federal Register. Please note: this further announcements concerning your doves not affect any obligation you might
response to your premarket notification submission the Electronic Product response to your premarker notheaton submission ave es under the Electronic Product nave under sections 551 through b 12 cFederal laws or regulations.

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Page 2

Under the Clinical Laboratory Improvement Amendments of 1988 (CLA-88), this device may
out of the may of the may in the minerified does, wou should contact the Under the Ciffical Laboratory improveinon. To determine if it does, you should contact the require a CLIA Complexity Sategorized on (CDC) at (770) 488-7655.

This letter will allow you to begin marketing your device as described in your 510(k) prematket This letter will allow you to begil nialiscung your device to a legally marketed
notification. The FDA finding of substantial equivalence of your device to notification. The ITA Inding of substantial oqur factive of thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and If you desire specific advice for your devices), please contact the Office of Compliance at
additionally 809.10 for in vitro diagnostic devices), please contactive of your de additionally 809.10 for m vitto diaguestions on the promotion and advertising of your device, (301) 594-4588. Additionally, for questions of the presses Also, please note the regulation please contact the Office of Comphance at (301) >> Teation"(21 CFR 807.97). Other general
entitled, "Misbranding by reference to premarket notification"(21 CFR 807.97). Oth entitled, "Misbranding by relectlifes under the Act may be obtained from the Division of Small
information on your responsibilities under the Act may be obtained from the 100 information on your responsibilities under (800) 638-2041 or (301) 443-6597, or at its
Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) - 1 Manufacturers 713515tailoo av fd . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Sincerely yours,

Steven Putman

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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Binax, Inc.
Binax, NOW® Streptococcus pneumoniae Urinary Antigen Test
Pressure if Contion Binax No"
510(k) Notification

APPENDIX B

INDICATIONS FOR USE FORM

510(k) Number (if known):

K991726

Device Name:

Binax NOW® Streptococcuss Binax NOW Borep
pneumoniae Urinary Antigen Test

Indications For Use:

The Binax NOW Streptococcus pneumoniae Urinary Antigen Test The Binax NOW® Streptococcus pneumoniae Orinary on of
is a rapid immunochromatographic as an adjunct to Streptococcus pneumoniae in human urine as an adjunct to is a rapid imman urine diagnosis of pneumococcal
culture for the presumptive diagnosis of pneumostic use the presumptive diagnosis or presumer ---------------------------------------------------------------------------------------------------------------------------------------pneumonia.

PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANCTHER PAGE IF NEDEDED)

45 be Norman ------------------------------------------------------------------------------Division Significal Laboratory Device 510(k) Number Over-The-Counter Use OR Prescription Use (Per 21 CFR 801.109)

(Optional Format 1-2-96)

Regulation Number and Section

§ 866.3740

Streptococcus spp. serological reagents.(a)
Identification. Streptococcus spp. serological reagents are devices that consist of antigens and antisera (excluding streptococcal exoenzyme reagents made from enzymes secreted by streptococci) used in serological tests to identifyStreptococcus spp. from cultured isolates derived from clinical specimens. The identification aids in the diagnosis of diseases caused by bacteria belonging to the genusStreptococcus and provides epidemiological information on these diseases. Pathogenic streptococci are associated with infections, such as sore throat, impetigo (an infection characterized by small pustules on the skin), urinary tract infections, rheumatic fever, and kidney disease.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 866.9.