The Thermo BioStar™ FLU OIA* A/B assay is an Optical ImmunoAssay test for the qualitative, rapid detection of influenza A and B viral antigens (nucleoproteins) extracted from nasal aspirate, nasopharyngeal swab, throat swab, and sputum specimens. This test is intended for in vitro diagnostic use to aid in the differential diagnosis of influenza A and B viral infections. The FLU OIA A/B test is not intended for detection of influenza C. Negative test results should be confirmed by cell culture.

Device Description

The FLU OIA A/B test involves the extraction and detection of a protein antigen unique to influenza A or B (nucleoprotein). The Optical ImmunoAssay technology enables the direct visual detection 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 an 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 surface retains the original gold color indicating a negative result.

AI/ML Overview

Here's an analysis of the provided text regarding the acceptance criteria and study for the FLU OIA® A/B device, structured according to your requested information:

Acceptance Criteria and Device Performance Study for FLU OIA® A/B

1. Table of Acceptance Criteria and Reported Device Performance

Performance Metric	Acceptance Criteria (Implied)	Reported Device Performance (FLU OIA® A/B)
Sensitivity (Influenza A)	Not explicitly stated	82.9% (95% C.I. = 75.3-89.0)
Sensitivity (Influenza B)	Not explicitly stated	63.6% (95% C.I.= 40.7-82.8%)
Reproducibility (Inter-Laboratory)	Not explicitly stated	96.6% across all sites (255/264)
Agreement with original FLU OIA (positive specimens)	Not explicitly stated	100% (95% Cl = 39.8 -100)
Overall Agreement with original FLU OIA	Not explicitly stated	100% (95% CI = 96.8 - 100)

Note: The document does not explicitly state pre-defined acceptance criteria values for sensitivity or agreement. The reported device performance is presented as the study outcome without direct comparison to a specified target. However, the FDA's clearance of the device implies these performance metrics were deemed acceptable.

2. Sample Size and Data Provenance for Test Set

Sample Size:
- Clinical Sample Comparison: 184 patients enrolled in a multi-center study. Data available for analysis included 151 specimens positive by culture (129 Influenza A, 22 Influenza B).
- Comparison to original FLU OIA: 112 retrospective frozen clinical specimens.
- Reproducibility (Inter-Laboratory): Not explicitly stated as a single number for samples, but "Individual panels were prepared, each containing nine blinded specimens and two controls." This was performed on "three different occasions" by "four different laboratories."
- Reproducibility (Intra-Laboratory): Not explicitly stated as a single number, but "testing specimens at or near the cut-off in multiple replications (n=20)."
Data Provenance:
- Clinical Sample Comparison: Multi-center study with geographically diverse clinical sites. The data is retrospective, as it's a "retrospective analysis of previously collected clinical data."
- Comparison to original FLU OIA: Retrospective frozen clinical specimens.
- Reproducibility: Not specified beyond "three POL or clinic sites, and one internal Thermo BioStar site." The specimens for reproducibility were "spiked with negative, low positive, moderate positive, and high positive specimens for each virus type."

3. Number of Experts and Qualifications for Ground Truth

The document does not explicitly state the number or qualifications of experts used to establish the ground truth.
The ground truth for the clinical sample comparison relied on "commercially available cell culture, with confirmation and typing by fluorescent antibody staining." This implies laboratory personnel with expertise in viral culture and fluorescent antibody staining were involved, but their specific qualifications or number are not detailed.

4. Adjudication Method for Test Set

The document does not describe any specific adjudication method (e.g., 2+1, 3+1). The ground truth was established by "commercially available cell culture, with confirmation and typing by fluorescent antibody staining."

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

No, a MRMC comparative effectiveness study was not conducted. This device is an in-vitro diagnostic (IVD) test, not an imaging or AI-assisted diagnostic tool for human readers. Its performance is compared to a historical reference method (viral culture) or a predicate device, not in terms of human reader improvement with AI assistance.

6. Standalone Performance Study

Yes, a standalone performance study was conducted. The performance characteristics for the FLU OIA® A/B (and the original FLU OIA) were established by comparing the device's output (positive/negative for Influenza A/B) directly against the ground truth (viral culture and fluorescent antibody staining). The reported sensitivities are standalone performance metrics.

7. Type of Ground Truth Used

The primary ground truth used for the clinical sample comparison was viral culture, with confirmation and typing by fluorescent antibody staining.

8. Sample Size for Training Set

The document does not mention a separate "training set" in the context of machine learning or AI. This device is an optical immunoassay, which does not typically involve training on datasets in the same way an AI algorithm would. The "Performance characteristics for the original AB FLU OIA assay were initially established in a multi-center study" but this refers to the initial validation of the technology, not a training set for a learning algorithm. Subsequent comparability studies were performed using "inactivated virus standards, live virus strains, and a panel of retrospective frozen clinical specimens."

9. How Ground Truth for Training Set Was Established

As noted above, a "training set" in the context of an AI algorithm is not applicable here. For the "Performance characteristics for the original AB FLU OIA assay," the ground truth would have been established through methods such as viral culture, as detailed for the clinical sample comparison. The comparability studies also relied on "inactivated virus standards" and "live virus strains" where the viral status would be known.

Summary

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510(k) SUMMARY (page 1 of 3) 8.0

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: K023556

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

. SUBMITTER'S NAME: Thermo BioStar, Inc.
ADDRESS: 331 South 104th Street .
TELEPHONE: (303) 530-3888 ext. 612 .
. FAX: (303) 581-6405
CONTACT PERSON: John G. Adams ●
DATE 510(k) SUMMARY PREPARED: October, 2002; revised March, 2003 .

B. Safety and effectiveness information required per [§807.92(a)(2)]:

TRADE OR PROPRIETARY NAME: FLU OIA® A/B .
. COMMON NAME: Influenza Rapid Assay
CLASSIFICATION NAME: Antigen, CF (including CF Controls), Influenza Virus A, B, C

C. Identification of legally marketed device to which we are comparing performance.

Device Technology:

Trade or Proprietary Name:	AB FLU OIA test kit
Regulatory Class:	I
Manufacturer:	Thermo BioStar
510(k) Number:	K981651

Historical Reference Method:

Viral Culture

Intended use of device { $807.92(a)(5)]:

The Thermo BioStar" FLU OIA* A/B assay is an Optical ImmunoAssay test for the qualitative, rapid detection of influenza A and B viral antigens (nucleoproteins) extracted from nasal aspirate, nasopharyngeal swab, throat swab, and sputum specimens. This test is intended for in vitro diagnostic use to aid in the differential diagnosis of influenza A and B viral infections. The FLU OIA A/B test is not intended for detection of influenza C. Negative test results should be confirmed by 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 3)

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 surface retains the original gold color indicating a negative result.

DEVICE COMPARISON:

Device Technology:

The FLU OIA A/B assay addressed in this submission is identical to the FLU OIA assay previously cleared in that:

Both assays are rapid diagnostic tests that utilize Optical ImmunoAssay technology ●
Both assays are used to detect and identify antigen proteins specific to influenza B . infections.
. Both assays can provide results in less than 20 minutes.
. Both assays are qualitative.
Neither assay is intended to detect influenza C . .

The FLU OIA A/B assay differs from the currently marketed FLU OIA assay in that:

The original FLU OIA assay (K981651) does not differentiate A from B influenza antigens. FLU OIA . A/B allows for the independent identification of viral type B antigens from the same specimen.

SUMMARY OF PERFORMANCE DATA:

ANALYTICAL and CLINICAL Comparison

Performance characteristics for the original AB FLU OIA assay were initially established in a multi-center study with geographically diverse clinical sites. The analytical sensitivity of the FLU OIA A/B test is equivalent to that of the FLU OIA test, as measured by comparability studies carried out using inactivated virus standards, live virus strains, and a panel of retrospective frozen clinical specimens.

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

Reproducibility

Inter-Laboratory

Representatives of three POL or clinic sites, and one internal Thermo BioStar site conducted reproducibility testing. Individual panels were prepared , each containing nine blinded specimens and two controls. Each panel was performed on three different occasions, by personnel from the four different laboratories. The samples consisted of throat swabs spiked with negative, low positive, moderate positive, and high positive specimens for each virus type. These samples were spiked onto swabs for analysis.

Overall reproducibility for the sample panel was 96.6% across all sites (255/264).

Intra-Laboratory

Reproducibility of the assay was evaluated by testing specimens at or near the cut-off in multiple replications (n=20). The cut-off was defined as the level of virus at which it would be expected that the assay would be positive 50% of the time and negative 50% of the time.

8.0

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

Clinical Sample Comparison

A retrospective analysis was conducted of previously collected clinical data comparing the FLU OIA test to commercially available cell culture, with confirmation and typing by fluorescent antibody staining. A total of 184 patients were enrolled into the multi-center study. Data available for analysis included 151 specimens that were positive by culture. Of the 151, 129 were confirmed as Influenza A and 22 were confirmed as Influenza B. Sensitivity to Influenza A is calculated as 82.9% (95%C.I. = 75.3-89.0), and sensitivity to Influenza B is calculated as 63.6% (95% C.I.= 40.7-82.8%)

The performance of the FLU OIA A/B assay was also compared to the original FLU OIA assay on 112 retrospective frozen clinical specimens. For positive specimens (4) agreement was 100% (95% Cl = 39.8 -100). Overall agreement was 100% (95% CI = 96.8 - 100)

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

Analytical testing was performed on both microbial and viral panels to assess specificity and cross reactivity.

Whole blood and several types of over the counter (OTC) products were evaluated to assess the potential for interference.

The results of the above described internal and external studies demonstrated that the FLU OIA A/B is safe and effective .

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Image /page/3/Picture/1 description: The image shows the logo for the Department of Health & Human Services. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" arranged around the perimeter. Inside the circle is an abstract symbol that resembles an eagle or bird in flight, composed of three curved lines.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

MAR 2 7 2003

Mr. John G. Adams Regulatory Affairs Thermo BioStar 331 South 104th Street Louisville, CO 80027

Re: K023556

Trade/Device Name: FLU OIA ® A/B Test Kit Regulation Number: 21 CFR 866.3330 Regulation Name: Influenza Virus Serological Reagents Regulatory Class: Class I Product Code: GNX Dated: January 25, 2003 Received: January 28, 2003

Dear Mr. Adams:

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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Page 2 -

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.

Steven Sutman

Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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INDICATIONS FOR USE STATEMENT 12.0

INDICATIONS FOR USE STATEMENT

510(k) Number (if known): K023556

FLU OIA® A/B Device Name:

Indications For Use:

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use
(Per 21 CFR 801.109)

Sledditu Poole

Over-The-Counter Use

(Optional Format 1-2-96)

Sign-Off 510(k) "Jumb

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.