(107 days)
The Clearview Advanced™ Strep A test is a rapid chromatographic immunoassay for the qualitative detection of Strep A antigen from throat swab specimens as an aid in the diagnosis of Group A Streptococcal infection.
The Clearview Advanced™ Strep A test is a qualitative, lateral flow immunoassay for the detection of Strep A carbohydrate antigen directly from a throat swab sample. To perform the test, Reagent 1 (R1) is added to the extraction tube which is coated with a mixture of conjugate antibodies and a lytic enzyme extraction reagent. The lytic enzyme is mixed with colloidal gold conjugated to rabbit anti-Strep A and a second colloidal gold control coniugate antibody. The reagents are dried onto the bottom of an extraction tube forming a red spot. The extraction/conjugate pellet is resuspended with R1 and the throat swab is added to the extraction tube. The Strep A antigen is extracted from the sample and the swab is removed. The test strip is immediately placed in the extracted sample. If Group A Streptococcus is present in the sample, it will react with the anti-Strep A antibody conjugated to the gold particle. The complex will then be bound by the anti-Strep A capture antibody and a visible red test line will appear, indicating a positive result. To serve as an onboard procedural control, the blue line observed at the control site prior to running the assay will turn red, indicating that the test has been performed properly. If Strep A antigen is not present, or present at very low levels, only a red control line will appear. If the red control line does not appear, or remains blue, the test result is invalid.
Here's a breakdown of the acceptance criteria and study details for the Clearview Advanced™ Strep A Test, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Metric | Acceptance Criteria (Implicit) | Reported Device Performance |
|---|---|---|
| Clinical Performance | ||
| Sensitivity | Not explicitly stated, but high sensitivity is crucial for diagnostic tests to minimize false negatives. | 91.5% (95% CI: 85.0% to 95.3%) |
| Specificity | Not explicitly stated, but high specificity is crucial to minimize false positives. | 95.0% (95% CI: 90.7% to 97.3%) |
| Analytical Sensitivity (Limit of Detection - LOD) | The concentration of Group A Streptococcus bacteria that produces positive results approximately 95% of the time. | 1 x 10^4 organisms/test |
| Analytical Specificity (Cross-Reactivity) | No false positives when tested against common commensal and pathogenic microorganisms. | All 38 tested microorganisms were negative at 1 x 10^6 organisms/test. |
| Reproducibility | Consistent results across different sites, days, and operators, especially for moderate positive and LOD concentrations. | Overall Detection:- Diluent (True Negative): 0% (0/179)- 1x10^5 (Moderate Positive): 99% (179/180)- 1x10^4 (LOD/C95 Concentration): 94% (170/180)- 3.2x10^3 (Near the cut-off/C50 Concentration): 49% (88/179) |
Note on Acceptance Criteria: The document does not explicitly state numerical acceptance criteria for sensitivity and specificity. However, regulatory bodies implicitly expect high performance from diagnostic tests for infectious diseases. The provided confidence intervals indicate a robust performance profile. For analytical sensitivity and specificity, the acceptance criteria are described directly in the text (e.g., "produces positive... approximately 95% of the time" for LOD, and "all... were negative" for cross-reactivity).
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size (Clinical Performance Test Set): A total of 297 throat swab specimens.
- Data Provenance:
- Country of Origin: United States.
- Retrospective or Prospective: Prospective clinical study.
- Study Design: Multi-center study conducted in 2008-2009 at five geographically diverse physician offices, clinics, and emergency departments.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
- The document does not specify the number of experts used to establish the ground truth or their qualifications. The ground truth ("bacterial culture") is an objective laboratory method rather than an expert interpretation in this context.
4. Adjudication Method for the Test Set
- The document does not describe an adjudication method. The comparison is directly between the Clearview Advanced Strep A test results and the bacterial culture results.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No, an MRMC comparative effectiveness study was not done. This study assesses the performance of a device (immunoassay) against a gold standard (bacterial culture), not how human readers improve with or without AI assistance.
6. Standalone Performance Study
- Yes, a standalone performance study was done. The entire clinical performance section describes the algorithm's (device's) performance without human intervention in interpreting the test result. The test is a qualitative, lateral flow immunoassay where the visual appearance of a line directly indicates a positive or negative result, and its accuracy is compared to the bacterial culture.
7. Type of Ground Truth Used
- Bacterial Culture. The clinical performance of the Clearview Advanced Strep A test was established by comparing its results to bacterial culture, which is considered the gold standard for diagnosing Group A Streptococcal infection.
8. Sample Size for the Training Set
- The document does not specify a separate training set or its sample size. The description of the clinical study refers to the "test set" or "evaluation set" for performance metrics. For traditional immunoassay devices like this, there isn't typically a distinct "training set" in the machine learning sense. The device's design and parameters are developed through analytical studies (e.g., LOD, cross-reactivity) rather than through training on a large dataset of patient samples.
9. How the Ground Truth for the Training Set Was Established
- Since there's no explicitly defined "training set" in the context of machine learning for this device, a ground truth establishment method for it is not applicable/not described. The robust design of the immunoassay, informed by analytical studies, serves as its "training" or development process.
{0}------------------------------------------------
13
SEP 0 4 2009
SUBMITTER
Binax, Inc. 10 Southgate Rd Scarborough, ME 04074 (207) 730-5824 (Office) (207) 730-5717(Fax)
CONTACT PERSON
Erin E. Kenaley Erin.Kenaley@invmed.com (email)
DATE PREPARED
August 13, 2009
TRADE NAME
Clearview Advanced ™ Strep A Test
COMMON NAME
Rapid Strep A test, Strep A dipstick test
CLASSIFICATION NAME
Antigens, All Groups, Streptococcus Spp. Serological Reagents (GTY) (per 21 CFR 866.3740)
PREDICATE DEVICES
Genzyme OSOM® Ultra Strep A Test (K992658)
DEVICE DESCRIPTION:
The Clearview Advanced™ Strep A test is a qualitative, lateral flow immunoassay for the detection of Strep A carbohydrate antigen directly from a throat swab sample. To perform the test, Reagent 1 (R1) is added to the extraction tube which is coated with a mixture of conjugate antibodies and a lytic enzyme extraction reagent.
The lytic enzyme is mixed with colloidal gold conjugated to rabbit anti-Strep A and a second colloidal gold control coniugate antibody. The reagents are dried onto the bottom of an extraction tube forming a red spot. The extraction/conjugate pellet is resuspended with R1 and the throat swab is added to the extraction tube. The Strep A antigen is extracted from the sample and the swab is removed. The test strip is immediately placed in the extracted sample. If Group A Streptococcus is present in the sample, it will react with the anti-Strep A antibody conjugated to the gold particle. The complex will then be bound by the anti-Strep A capture antibody and a visible red test line will appear, indicating a positive result. To serve as an onboard procedural control, the blue line observed at the control site prior to running the assay will turn red, indicating that the test has been performed properly. If Strep A antigen is not present, or present at very low levels, only a red control line will appear. If the red control line does not appear, or remains blue, the test result is invalid.
{1}------------------------------------------------
INTENDED USE
The Clearview Advanced Strep A test is a rapid chromatographic immunoassay for the qualitative detection of Strep A antigen from throat swab specimens as an aid in the diagnosis of Group A Streptococcal infection.
TECHNOLOGICAL CHARACTERISTICS
The Clearview Advanced Strep A test and the Genzyme OSOM Ultra Test utilize similar lateral flow immunochromatographic technology. Both tests are rapid immunoassays that employ specific antibodies immobilized onto a solid phase to capture and visualize Group A Streptococcal antigens.
PERFORMANCE SUMMARY
Clinical Performance
The clinical performance of the Clearview Advanced Strep A test was established in a multi-center, prospective clinical study conducted in 2008-2009 at five geographically diverse physician office, clinics, and emergency departments within the United States.
A total of 297 throat swab specimens were evaluated by comparing the Clearview Advanced Strep A test to bacterial culture. In this study, sensitivity was 91.5% (95% Cl 85.0% to 95.3%) and specificity was 95.0% (95% Cl 90.7% to 97.3%).
| Bacterial Culture Results | |||
|---|---|---|---|
| Positive | Negative | ||
| Clearview Advanced Strep A | Positive | 107 | 9 |
| Test Results | Negative | 10 | 170 |
| Total | 117 | 179 |
denotes 95% Confidence Interval Sensitivity-91.5% (85.0% to 95.3%)* Specificity-95.0% (90.7% to 97.3%)*
Analytical Sensitivity (Limit of Detection)
The Clearview Advanced Strep A test limit of detection (LOD), defined as the concentration of Group A Streptococcus bacteria that produces positive Clearview Advanced Strep A test results approximately 95% of the time, was identified by evaluating different concentrations of Group A Streptococcus in the Clearview Advanced. Strep A test. The detection limit of the Clearview Advanced Strep A test was determined to be 1x104 organisms/test.
Analytical Specificity (Cross-Reactivity)
To determine the analytical specificity of the Clearview Advanced Strep A test, 38 commensal and pathogenic microorganisms including bacteria, viruses and yeast that may be present in the mouth or throat were tested. All of the following microorganisms were negative when tested at a concentration of 1x10° organisms/test.
Streptococcus salivarius Haemophilus parainfluenzae. Streptococcus Group B Neisseria subflava Proteus vulgaris Arcanobacterium haemolyticum Haemophilus influenzae Streptococcus Group C Pseudomonas aeruginos Streptococcus Group F Bordetella pertussis Klebsiella pneumoniae
{2}------------------------------------------------
Streptococcus Group G. Streptococcus anginosus Streptococcus mitis Streptococcus mutans Streptococcus oralis Streptococcus pneumoniae Streptococcus sanguis
Candida albicans Corynebacterium diphtheriae Enterococcus faecalis Enterococcus faecium. Escherichia coli Fusobacterium necrophorum. Haemophilus parahaemolyticus
Moraxella catarrhalis Moraxella lacunata Neisseria gonormoeae Neisseria lactamica Neisseria meningitides Neisseria mucosa Neisseria sicca
Serratia marcescens. Staphylococcus aureus Staphylococcus epidermidis Staphylococcus haemolyticus Yersinia enterocolitica
Reproducibility
A blind study of the Clearview Advanced Strep A test was conducted at 3 separate sites using panels of blind coded specimens. Participants tested each sample multiple times on 5 different days, with no significant difference between runs (5 different days), between sites (3 sites), and between operators (6 operators). The results are presented below:
| Sample | Site 1Detection | Site 2Detection | Site 3Detection | OverallDetection |
|---|---|---|---|---|
| Diluent (True Negative) | 0% (0/60) | 0% (0/60) | 0% (0/59)** | 0% (0/179) |
| 1x105 (Moderate Positive) | 100% (60/60) | 98% (59/60) | 100% (60/60) | 99% (179/180) |
| 1x104 (LOD/C95 Concentration) | 100% (60/60) | 100% (60/60) | 83% (50/60) | 94% (170/180) |
| 3.2x103 (Near the cut-off/C50Concentration) | 80% (48/60) | 58% (34/59)* | 10% (6/60) | 49% (88/179) |
2 invalid results excluded from the data analysis
Signed Angela Lupdale Date 8/14/09
Angela Drysdale Sr. Manager of Clinical Affairs
{3}------------------------------------------------
Image /page/3/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with three lines representing its body and wings. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" are arranged in a circular pattern around the eagle.
DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Building 66 Silver Spring, MD 20993
Erin E. Kenalev Clinical Affairs Specialist Binax, Inc. 10 Southgate Road Scarborough, ME 04074
Re: K091489
Trade/Device Name: Clearview Advanced TM Strep A Test Regulation Number: 21 CFR 866.3740 Regulation Name: Streptococcus spp. exo-enzyme reagents Regulatory Class: Class I Product Code: GTY Dated: August 13, 2009 Received: August 19, 2009
Dear Ms. Kenaley:
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.
SEP 0 4 2009
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
{4}------------------------------------------------
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). 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 (301) 594-3084. 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,
Say cazino
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
{5}------------------------------------------------
Indication for Use
510(k) Number (if known): K091489
Device Name: Clearview Advanced™ Strep A Test
Indication For Use:
The Clearview Advanced™ Strep A test is a rapid chromatographic immunoassay for the qualitative detection of Strep A antigen from throat swab specimens as an aid in the diagnosis of Group A Streptococcal infection.
Prescription Use ਮ (21 CFR Part 801 Subpart D)
And/Or
Over the Counter Use _ (21 CFR Part 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OVD)
Freddie Leach
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K691489
Page 1 of 1
§ 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.