The BioStar® AB FLU OIA® assay is an Optical ImmunoAssay (OIA) test for the qualitative, rapid detection of influenza A and B viral antigen (nucleoprotein) from nasal aspirate, nasopharyngeal swab, throat swab, or sputum specimens. This test is intended for in vitro diagnostic use to aid in the diagnosis of influenza A and B viral infections. The AB FLU OIA test is not intended to detect influenza C. Negative test results should be confirmed by cell culture.

Device Description

The AB FLU OIA test involves the extraction and detection of a protein antigen unique to influenza A or B (nucleoprotein). The Opical ImmunoAssay technology enables the direction of a physical change in the optical thickness of molecular thin films. This change is a result of antigen-antibody binding on an optical surface (silicon wafer). When extracted specimen is placed directly on the optical surface, the immobilized specific antibodies capture the antigen. After washing, the substrate is added, increasing the thickness (Mass Enhancement) of the molecular thin film. This change in thickness alters the reflected light path and is visually perceived as a color change. Slight changes in optical thickness produce a distinct visible color change. A positive result appears as a purple spot on the predominant gold background. When antigen is not present in the specimen, no binding takes place. Therefore, the optical thickness remains unchanged and the original gold indicating a negative result.

AI/ML Overview

Here's an analysis of the provided text regarding the acceptance criteria and study for the BioStar® AB FLU OIA Test Kit:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria in terms of specific sensitivity and specificity thresholds. Instead, it presents the "relative sensitivity" and "relative specificity" as the results of the clinical study for different specimen types. The conclusion states that these results, combined with analytical sensitivity and specificity, demonstrate that the device is safe and effective. Therefore, the reported performance itself serves as the basis for acceptance. I will present the reported clinical performance.

Test Parameter / Specimen Type	Reported Device Performance
Clinical Performance
Nasal Aspirate (NA)	Relative Sensitivity: 88.4% Relative Specificity: 69.4%
Nasopharyngeal Swab (NPS)	Relative Sensitivity: 83.3% Relative Specificity: 76.2%
Throat Swab (TS)	Relative Sensitivity: 62.1% Relative Specificity: 79.5%
Sputum (SP)	Relative Sensitivity: 81.1% Relative Specificity: 51.5%
Analytical Sensitivity
Hong Kong/68 H3N2 (A)	$2.6 \times 10^3$ TCID/test
Shangdong/9/93 H3N2 (A)	$1.2 \times 10^4$ TCID/test
Texas/36/91 H1N1 (A)	$7.1 \times 10^3$ TCID/test
Wuhan/359/95 H3N2 (A)	$1.3 \times 10^3$ TCID/test
Bayern/7/95 H1N1 (A)	$2.3 \times 10^3$ TCID/test
Singapore/1/57 H2N2 (A)	$5.0 \times 10^2$ TCID/test
Hong Kong/156/97 H5N1 (A)	$5.3 \times 10^3$ TCID/test
Panama/45/90 (B)	$1.3 \times 10^4$ TCID/test
Beijing/184/93 (B)	$9.4 \times 10^2$ TCID/test
Guangdong/5/94 (B)	$6.0 \times 10^3$ TCID/test
Victoria/2/87 (B)	$1.2 \times 10^3$ TCID/test
Analytical Specificity	No positive result for listed organisms/viruses
Interfering Substances	No decrease in signal for Influenza A or B in presence of blood, mouthwashes, throat sprays, cough lozenges, or cough/cold elixirs. No positive signal without virus present.

2. Sample Size Used for the Test Set and Data Provenance

Sample Size for Test Set: 184 individuals exhibiting influenza-like symptoms.
Data Provenance:
- Country of Origin: United States (indicated by "Rocky Mountain region," "Midwest region," and "Southwestern region" for the three study sites).
- Retrospective or Prospective: Prospective, as specimens were collected from individuals exhibiting symptoms as part of the evaluation.

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 or qualifications of experts used to establish the ground truth. It states that the ground truth was determined by "confirmed culture from any specimen type." This implies trained laboratory personnel performed and interpreted the cultures, but their specific qualifications (e.g., years of experience, specific certifications) are not provided.

4. Adjudication Method for the Test Set

The document does not describe a formal adjudication method (like 2+1 or 3+1) for discordant results between the device and the ground truth (cell culture). The "relative sensitivity and specificity" were calculated by comparing the AB FLU OIA assay results directly to the 14-day culture results.

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

No, an MRMC comparative effectiveness study involving human readers and AI assistance was not performed or described. This is an in vitro diagnostic device (test kit) meant for laboratory use, not a device that directly assists human readers/clinicians in interpreting images or data. The comparison is between the test kit and a conventional laboratory method (cell culture).

6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done

Yes, this study represents a standalone performance evaluation of the device. The AB FLU OIA assay is a laboratory test kit, and its performance was assessed independently against cell culture without direct human interpretation influencing its results.

7. The Type of Ground Truth Used

The primary ground truth used for determining clinical performance (relative sensitivity and specificity) was cell culture (specifically, "14-day culture"). For analytical sensitivity, the ground truth was also cell culture (TCID/test values estimated by inoculating dilutions into cell culture).

8. The Sample Size for the Training Set

The document does not explicitly mention a "training set" for the device, as it describes a finished diagnostic test kit rather than a machine learning algorithm that undergoes a distinct training phase with a specific dataset. The evaluation presented focuses on the device's performance characteristics.

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

As no specific training set is identified in the context of machine learning, this question is not directly applicable. If considering the development process of the assay, the ground truth for establishing acceptable performance characteristics (e.g., antibody binding, optical properties) would have been determined through internal validation using known positive and negative controls, spiked samples, and reference strains, likely confirmed by gold standard methods (like cell culture or genetic sequencing) during the assay's development. However, these specific developmental "training" details are not provided in this 510(k) summary.

Summary

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NOV 2 5 1998

1981651

Response to 9/11/98 Review Summary: BioStar®, Inc. AB FLU OIA Test Kit - K981651

8.0 510(k) SUMMARY (page 1 of 5)

510(k) SUMMARY

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

The assigned 510(k) number is:

A. Safety and effectiveness information required per [§807.92(a)(1)]:

SUBMITTER'S NAME: BioStar, Inc. .
ADDRESS: 6655 Lookout Rd. Boulder, CO 80301 ●
TELEPHONE: (303) 530-3888 ext. 603 ●
FAX: (303) 530-6601 .
CONTACT PERSON: Roger C. Briden .
DATE 510(k) SUMMARY PREPARED: September 18, 1998 .
B. Safety and effectiveness information required per [§807.92(a)(2)]:
TRADE OR PROPRIETARY NAME: AB FLU OIA® ●
COMMON NAME: Influenza Assay
. CLASSIFICATION NAME: Direct Antigen Detection Assay, Influenza Virus A, B

C. Identification of legally marketed device to which we are claiming equivalence [§807.92(a)(3)]:

TRADE OR PROPRIETARY NAME: Directigen® Flu A .
. REGULATORY CLASS: Class I
PRODUCT CODE: 83GNT .
MANUFACTURER: Becton Dickinson® and Co. .
. 510(k) NUMBER: K902609

Note: Performance of the AB FLU OIA product was established versus cell culture.

D. Description of device [§807.92(a)(4)}:

Principle of the Test:

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8.0 510(k) SUMMARY (page 2 of 5)

Device Components:

The AB FLU OIA test kit contains the following:

Sample Diluent Reagent 1: Specimen Extraction Reagent Reagent 2: Conjugate Wash Substrate Positive Control Negative Control Extraction Tubes Test Devices Transfer Pipettes Sterile Rayon Swabs

E. Intended use of device [§807.92(a)(5)]:

F. Technological characteristics [§807.92(a)(6)]:

Technological Characteristic	Predicate Device (Directigen Flu A)	Our Device (AB FLU OIA)
Intended Use	The Directigen Flu A Test is an in vitroenzyme immunoassay (EIA) membrane testfor the direct rapid and qualitative detectionof influenza A viral antigen from suitablespecimens of symptomatic patients.Nasopharyngeal wash and aspiratespecimens have been shown to be superior tonasopharyngeal and throat swab specimensand are the specimens of choice with theDirectigen Flu A Test.	The BioStar® AB FLU OIA® assay isan Optical ImmunoAssay (OIA) testfor the qualitative, rapid detection ofinfluenza A and B viral antigen(nucleoprotein) from nasal aspirate,nasopharyngeal swab, throat swab, orsputum specimens. This test isintended for in vitro diagnostic use toaid in the diagnosis of influenza A andB viral infections. The AB FLU OIAtest is not intended to detect influenzaC. Negative test results should beconfirmed by cell culture.
Detection	Detects Influenza A nucleoproteins.	Detects Influenza A and Bnucleoproteins.
Technology	Enzyme Immunoassay (EIA) Membrane	Optical Immunoassay (OIA)
Specimens Evaluated	Nasopharyngeal wash, nasopharyngealaspirate, nasopharyngeal swab, throat swab.	Sputum, nasal aspirate,nasopharyngeal swab, throat swab.

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8.0 510(k) SUMMARY (page 3 of 5)

G. Summary of nonclinical testing [§807.92(b)(1)]:

Analytical Sensitivity:

The analytical sensitivity was evaluated using 11 influenza strains: 7 influenza B strains. Duplicate dilutions of each viral strain were prepared in Phosphate Buffered Saline (PBS) and tested according to the AB FLU OIA Test Procedure. Viral detection limit tested in the AB FLU OIA test (TCID //test) was determined by inoculating dilutions in cell culture to estimate TCID

Viral Strain	Viral Type	Detection Limit
Hong Kong/68 H3N2	A	$2.6 x 10^3$
Shangdong/9/93 H3N2	A	$1.2 x 10^4$
Texas/36/91 H1N1	A	$7.1 x 10^3$
Wuhan/359/95 H3N2	A	$1.3 x 10^3$
Bayern/7/95 H1N1	A	$2.3 x 10^3$
Singapore/1/57 H2N2	A	$5.0 x 10^2$
Hong Kong/156/97 H5N1	A	$5.3 x 10^3$
Panama/45/90	B	$1.3 x 10^4$
Beijing/184/93	B	$9.4 x 10^2$
Guangdong/5/94	B	$6.0 x 10^3$
Victoria/2/87	B	$1.2 x 10^3$

Reactivity:

To demonstrate reactivity across a broad spectrum of influenza strains, the AB FLU OIA test was performed on a number of additional human and non-human strains.

A/NWS/33 (H1N1) A/Swine/1976/31 A/New Jersey/8/76 (HswN1) A/Japan/170/62 (H2N2) A/Puerto Rico/8/34 (H1N1) A2/Taiwan/1/64 (H2N2) A/Port Chalmers/1/73 (H3N2) A/Victoria/3/75 (H3N2) A/Duck/Ukraine/1/63 (H3N8) A/Duck/Czechoslovakia/56 (H4N6) A/Chicken/Hong Kong/1203/97 (H5N1) A/Duck/Pennsylvania/10218/84 (H5N2) A/Shearwater/Australia/1/72 (H6N5) A/Equine 1/Prague/1/56 (H7N7) A/Turkey/Oregon/1/74 (H7N3) A/Turkey/Ontario/6118/68 (H8N4) A/Chick/Germany/N/48 (H10N7)

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8.0 510(k) SUMMARY (page 4 of 5)

A/Duck/England/56 (H11N6) A/Duck/Alberta/60/76 (H12N6) A/Gull/Maryland/704/77 (H13N6)

Analytical Specificity (Cross Reactivity):

To determine the analytical specificity of the AB FLU OIA test, the organisms and viruses listed in the bacterial and viral panels presented in the product package insert were grown in culture and tested at appropriate concentrations. A sample of each organism and virus was tested in duplicate. Cell density or viral titer was confirmed by plating an aliquot of suspension, growing the organism or virus, and counting the number of colonies or plaques formed. None of the organisms or viruses listed in the panels gave a positive result in the AB FLU OIA test.

Interfering Substances:

A variety of substances were obtained which interfere with the effectiveness of the AB FLU OIA test if encountered during the collection of specimens. Each substance was prepared in a manner and concentration so as to exceed the likely conditions and amounts found in situ. Each substance was tested in three independent analyses: In the absence of influenza virus, in the presence of only Influenza A (A/Hong Kong), and in the presence of only Influenza B (B/Panama). In addition, a saline control was tested in the same manner. All assays were run per the testing procedure described in the package insert. None of the specimens tested gave a positive signal when virus was not present in the sample. No decrease in signal strength was noted for either influenza A or B in the presence of either blood, or several commercially available mouth washes, throat sprays, cough lozenges, or cough/cold elixirs.

H. Summary of clinical testing [§807.92(b)(2)]:

The performance of the AB FLU OIA assay was compared to conventional methods for influenza culture in an cvaluation of clinical specimens. In a three-site study to compare the AB FLU OIA assay with culture, any combination of dual throat and dual nasopharyngeal swabs, nasal aspirate and sputum specimens were collected from 184 individuals exhibiting influenza-like symptoms. Patients of any age or sex were included in this study.

The influenza prevalence rate by site, as determined by confirmed culture from any speciment type, was 56.1% at site I (Rocky Mountain region), 56.9% at site 2 (Midwest region), and 41.0% at site 3 (Southwestern region). The table below summarizes the sensitivity and specificity of the AB FLU OIA test relative to 14-day culture for the four specimen types collected during the clinical study. The four specimen types identified in the table are nasal aspirate (NA), nasopharyngeal swab (NPS), throat swab (TS), and sputum (SP). For additional information regarding data collection and analysis, see the product package insert.

D. Specimen Type	E. Relative Sensitivity	F. Relative Specificity
NA	88.4 %	69.4%
NPS	83.3%	76.2%
TS	62.1%	79.5%
SP	81.1%	51.5%

Conclusions from nonclinical / clinical testing [§807.92(b)(3)].

In evaluating the cross reactivity of the AB FLU OIA test with organisms and viruses listed in the bacterial and viral panels presented in the product package insert, none of the organisms or viruses gave a positive result in the AB FLU OIA test. At levels exceeding those likely be encountered in situ during sample collection, neither blood, nor several commercially available mouthwashes, throat sprays, cough lozenges, or cough/cold elixirs interfered with the test. These results combined with the analytical sensitivity, along with the relative sensitivity and specificity calculated from the clinical study data demonstrate that the AB FLU OIA test is safe and effective.

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Response to 9/11/98 Review Summary: BioStar®, Inc. AB FLU OIA Test Kit - K981651

8.0 510(k) SUMMARY (page 4 of 5)

J. Additional information [§807.92(d)]:
:

No additional information has been requested by FDA at this time.

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Image /page/5/Picture/1 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features the department's name in a circular arrangement around an emblem. The emblem consists of three stylized human profiles facing right, with flowing lines beneath them, resembling a ribbon or fabric.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

NOV 25 1998

Roger Briden, Ph.D. Director, RA/OA BioStar, Inc. 6655 Lookout Road Boulder, CO 80301

Re: K981651 Trade Name: BioStar® AB FLU OIA Regulatory Class: I Product Code: GNX Dated: September 18, 1998 Received: September 22, 1998

Dear Dr. Briden:

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 OS 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 (770)488-7655.

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 your 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 (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. 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 (800) 638-2041 or at (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"

Sincerely yours,

Steven Sutman

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): K981651

Device Name: BioStar®, Inc. AB FLU OIA

Indications For Use: The BioStar® FLU OIA assay is an Optical ImmunoAssay (OIA) test for the qualitative, rapid detection of influenza A and B viral antigen (nucleoprotein) from nasal aspirate, nasopharyngeal swabs, throat swabs, or sputum specimens. This test is intended for in vitro use to aid in influenza A and B viral infections. The FLU OlA is not intended to detect influenza C. Negative test results should be confirmed by culture [isolation].

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Woody Duboes.

sion of Clinical Laboratory Devices 510(k) Number.

Prescription Use X (Per 21 CFR 801.109)

Over-The-Counter Use

(Optional Format 1-2-96)

Regulation Number and Section

§ 866.3328 Influenza virus antigen detection test system.

(a)
Identification. An influenza virus antigen detection test system is a device intended for the qualitative detection of influenza viral antigens directly from clinical specimens in patients with signs and symptoms of respiratory infection. The test aids in the diagnosis of influenza infection and provides epidemiological information on influenza. Due to the propensity of the virus to mutate, new strains emerge over time which may potentially affect the performance of these devices. Because influenza is highly contagious and may lead to an acute respiratory tract infection causing severe illness and even death, the accuracy of these devices has serious public health implications.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The device's sensitivity and specificity performance characteristics or positive percent agreement and negative percent agreement, for each specimen type claimed in the intended use of the device, must meet one of the following two minimum clinical performance criteria:
(i) For devices evaluated as compared to an FDA-cleared nucleic acid based-test or other currently appropriate and FDA accepted comparator method other than correctly performed viral culture method:
(A) The positive percent agreement estimate for the device when testing for influenza A and influenza B must be at the point estimate of at least 80 percent with a lower bound of the 95 percent confidence interval that is greater than or equal to 70 percent.
(B) The negative percent agreement estimate for the device when testing for influenza A and influenza B must be at the point estimate of at least 95 percent with a lower bound of the 95 percent confidence interval that is greater than or equal to 90 percent.
(ii) For devices evaluated as compared to correctly performed viral culture method as the comparator method:
(A) The sensitivity estimate for the device when testing for influenza A must be at the point estimate of at least 90 percent with a lower bound of the 95 percent confidence interval that is greater than or equal to 80 percent. The sensitivity estimate for the device when testing for influenza B must be at the point estimate of at least 80 percent with a lower bound of the 95 percent confidence interval that is greater than or equal to 70 percent.
(B) The specificity estimate for the device when testing for influenza A and influenza B must be at the point estimate of at least 95 percent with a lower bound of the 95 percent confidence interval that is greater than or equal to 90 percent.
(2) When performing testing to demonstrate the device meets the requirements in paragraph (b)(1) of this section, a currently appropriate and FDA accepted comparator method must be used to establish assay performance in clinical studies.
(3) Annual analytical reactivity testing of the device must be performed with contemporary influenza strains. This annual analytical reactivity testing must meet the following criteria:
(i) The appropriate strains to be tested will be identified by FDA in consultation with the Centers for Disease Control and Prevention (CDC) and sourced from CDC or an FDA-designated source. If the annual strains are not available from CDC, FDA will identify an alternative source for obtaining the requisite strains.
(ii) The testing must be conducted according to a standardized protocol considered and determined by FDA to be acceptable and appropriate.
(iii) By July 31 of each calendar year, the results of the last 3 years of annual analytical reactivity testing must be included as part of the device's labeling. If a device has not been on the market long enough for 3 years of annual analytical reactivity testing to have been conducted since the device received marketing authorization from FDA, then the results of every annual analytical reactivity testing since the device received marketing authorization from FDA must be included. The results must be presented as part of the device's labeling in a tabular format, which includes the detailed information for each virus tested as described in the certificate of authentication, either by:
(A) Placing the results directly in the device's § 809.10(b) of this chapter compliant labeling that physically accompanies the device in a separate section of the labeling where the analytical reactivity testing data can be found; or
(B) In the device's label or in other labeling that physically accompanies the device, prominently providing a hyperlink to the manufacturer's public Web site where the analytical reactivity testing data can be found. The manufacturer's home page, as well as the primary part of the manufacturer's Web site that discusses the device, must provide a prominently placed hyperlink to the Web page containing this information and must allow unrestricted viewing access.
(4) If one of the actions listed at section 564(b)(1)(A)-(D) of the Federal Food, Drug, and Cosmetic Act occurs with respect to an influenza viral strain, or if the Secretary of Health and Human Services (HHS) determines, under section 319(a) of the Public Health Service Act, that a disease or disorder presents a public health emergency, or that a public health emergency otherwise exists, with respect to an influenza viral strain:
(i) Within 30 days from the date that FDA notifies manufacturers that characterized viral samples are available for test evaluation, the manufacturer must have testing performed on the device with those viral samples in accordance with a standardized protocol considered and determined by FDA to be acceptable and appropriate. The procedure and location of testing may depend on the nature of the emerging virus.
(ii) Within 60 days from the date that FDA notifies manufacturers that characterized viral samples are available for test evaluation and continuing until 3 years from that date, the results of the influenza emergency analytical reactivity testing, including the detailed information for the virus tested as described in the certificate of authentication, must be included as part of the device's labeling in a tabular format, either by:
(A) Placing the results directly in the device's § 809.10(b) of this chapter compliant labeling that physically accompanies the device in a separate section of the labeling where analytical reactivity testing data can be found, but separate from the annual analytical reactivity testing results; or
(B) In a section of the device's label or in other labeling that physically accompanies the device, prominently providing a hyperlink to the manufacturer's public Web site where the analytical reactivity testing data can be found. The manufacturer's home page, as well as the primary part of the manufacturer's Web site that discusses the device, must provide a prominently placed hyperlink to the Web page containing this information and must allow unrestricted viewing access.