The Influenza A/B Rapid Test is a qualitative immunoassay for the rapid detection of Influenza A/B viral antigens from throat swab specimens. This test is intended for professional in vitro diagnostic use to aid in the diagnosis of Influenza infections, and to gather epidemiological information for detection of Influenza outbreaks. When used for diagnosis, negative assay results should be confirmed by cell culture. This assay does not detect the presence of Influenza C viral antigens.

Device Description

The Influenza A/B Rapid Test consists of swabs, reaction cups, test strips, and reagent solutions. The test detects the viral nucleoprotein associated with the viral nucleic acid. The nucleoprotein is released by lysing the virus envelop with the lysis/elution solution. Since the nucleoprotein is type specific only (not subtype specific), the test uses two pairs of monoclonal antibodies – one pair is specific for Influenza A, the other is specific for Influenza B. The antibody pairs are conjugated to either biotin or digoxigenin. In the presence of the viral antigen, a sandwich complex is formed, consisting of the biotin-conjugated antibody, the nucleoprotein, and the digoxigenin-conjugated antibody. When the test strip is placed in the reaction cup, the complex migrates chromatographically, solubilizing colloidal gold particles incorporated in the red pad of the strip. The colloidal gold particles bind to the digoxigenin of the complex, which is then bound by the biotin to the immobilized streptavidin on the strip (positive result line). Any excess gold particles continue to migrate to the second line (control line), which then becomes visible. This indicates the correct chromatographic migration.

AI/ML Overview

Here's an analysis of the provided information regarding the acceptance criteria and study for the Roche Diagnostics Influenza A/B Rapid Test:

1. Table of Acceptance Criteria and Reported Device Performance

The submission does not explicitly state "acceptance criteria" as a separate, pre-defined target. Instead, it presents performance metrics of the device and compares them directly to a predicate device. The implied acceptance criteria are that the device should perform comparably to or better than the predicate device.

Performance Metric	Predicate Device (Biostar Flu OIA)	Roche Diagnostics Influenza A/B Rapid Test	Implied Acceptance Criterion (Target)	Met?
Sensitivity	62%	68.4%	At least 62% (comparable or better)	Yes
Specificity	80%	80.7%	At least 80% (comparable or better)	Yes

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

The document does not explicitly state the sample size used for the test set or the data provenance (e.g., country of origin, retrospective/prospective nature of the study). This information is crucial for evaluating the robustness and generalizability of the reported performance.

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 or their qualifications for establishing the ground truth for the test set.

4. Adjudication Method for the Test Set

The document does not describe any adjudication method used for the test set.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size

No MRMC comparative effectiveness study is mentioned. The study described focuses on the direct performance of the device against a known ground truth, not on human reader performance with or without AI assistance.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done

Yes, a standalone performance study was done. The reported sensitivity and specificity are for the device (the "immunoassay") itself, operating without human interpretation in the results. The 'read results' step in the procedure implies a qualitative visual interpretation of the test strip, but the performance metrics are attributed to the device's ability to detect the antigen, not human accuracy in reading the strip.

7. The Type of Ground Truth Used

The document states, "When used for diagnosis, negative assay results should be confirmed by cell culture." This strongly suggests that cell culture was used as the ground truth for determining the presence or absence of Influenza A/B viral antigens in the specimens used for performance evaluation. Cell culture is generally considered a gold standard for viral detection.

8. The Sample Size for the Training Set

The document does not provide information about a "training set" or its sample size. This type of device (a rapid immunoassay) typically undergoes assay development and validation, rather than machine learning-style training. The performance reported likely reflects studies on a cohort of specimens representative of the intended use population.

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

As there's no mention of a "training set" in the context of machine learning, this question isn't directly applicable. If a training phase for the assay's development (e.g., optimizing antibody concentrations) was implied, the ground truth would have been established through methods like cell culture or validated reference materials during that process. However, the immediate document doesn't detail this.

Summary

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510(k) Summary
Introduction	According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence.
1) Submitter name, address, contact	Roche Diagnostics Corporation9115 Hague Rd.Indianapolis, IN 46250(317) 845-2000Contact Person: Luann OchsDate Prepared: September 8, 1999.
2) Device name	Proprietary name: Roche Diagnostics Influenza A/B Rapid TestCommon name: Influenza virus detection reagentsClassification name: Antigens, CF (including CF control), influenza virus A, B, C
3) Predicate device	We claim substantial equivalence to the Biostar Flu OIA, optical immunoassay for the rapid detection of influenza A and B.

Continued on next page### 510(k) Summarv

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510(k) Summary, Continued

4) DeviceDescription	The Influenza A/B Rapid Test consists of swabs, reaction cups, test strips,and reagent solutions.
	The test detects the viral nucleoprotein associated with the viral nucleic acid.The nucleoprotein is released by lysing the virus envelop with thelysis/elution solution. Since the nucleoprotein is type specific only (notsubtype specific), the test uses two pairs of monoclonal antibodies – one pairis specific for Influenza A, the other is specific for Influenza B. The antibodypairs are conjugated to either biotin or digoxigenin.
	In the presence of the viral antigen, a sandwich complex is formed, consistingof the biotin-conjugated antibody, the nucleoprotein, and the digoxigenin-conjugated antibody. When the test strip is placed in the reaction cup, thecomplex migrates chromatographically, solubilizing colloidal gold particlesincorporated in the red pad of the strip. The colloidal gold particles bind to thedigoxigenin of the complex, which is then bound by the biotin to theimmobilized streptavidin on the strip (positive result line). Any excess goldparticles continue to migrate to the second line (control line), which thenbecomes visible. This indicates the correct chromatographic migration.
5) Intended use	The Influenza A/B Rapid Test is a qualitative immunoassay for the rapiddetection of Influenza A/B viral antigens from throat swab specimens. Thistest is intended for professional in vitro diagnostic use to aid in the diagnosisof Influenza infections, and to gather epidemiological information fordetection of Influenza outbreaks. When used for diagnosis, negative assayresults should be confirmed by cell culture. This assay does not detect thepresence of Influenza C viral antigens.

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510(k) Summary, Continued

Comparison to predicate device

The Roche Diagnostics Influenza A/B Rapid Test is substantially equivalent to other products in commercial distribution intended for similar use. Most notably it is substantially equivalent to the currently marketed Biostar Flu AB OIA.

Feature	RDC Influenza A/B Rapid Test	Biostar Flu OIA
Intended use	Detection of Influenza A and B viral antigen	Detection of Influenza A and B viral antigen
Indication for use	Aid in the diagnosis of influenza A or B viral infections.	Aid in the diagnosis of influenza A or B viral infections.
Sample type	Throat swab	Throat swab, nasal aspirate, nasopharyngeal swab, or sputum.
Test Principle	Direct visualization of antigen-antibody complex binding to a surface.	Direct visualization of antigen-antibody complex binding to a surface.
Results	Positive or negative qualitative results	Positive or negative qualitative results
Quality control	Internal procedural quality control, external quality control solutions	Internal procedural quality control, external quality control solutions
Performance	Sensitivity 68.4%Specificity 80.7%	Sensitivity 62%Specificity 80%

Continued on next page

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510(k) Summary, Continued

6) Comparison to predicate device, continued

Differences

Feature	RDC Influenza A/BRapid Test	Biostar Flu OIA
Procedure	Rapid, simple procedure:1. Extract sample in solution for 1 minute.2. Add antibody reagents and mix.3. Place test strip in solution.4. Read results after 10 minutes.	Complicated, long procedure:1. Extract sample in solution for 3 minutes. Add reagent.2. Pipet one drop of sample onto test surface. Wait 6 minutes.3. Wash the test surface.4. Blot the test surface.5. Add substrate reagent. Wait 6 minutes.6. Wash the test surface.7. Blot test surface.8. Read results.
Total Assay Time	12 minutes	20 minutes
Incubation Time	10 minutes	15 minutes

Benefits:

The RDC Influenza A/B Rapid Test is easier to perform than the Biostar Flu OIA. The Influenza A/B Rapid Test has fewer procedural steps, and can be completed in about 12 minutes, versus about 20 minutes for the Biostar Flu OIA. Both tests utilize throat swab specimens, and contain antibodies to viral nucleoprotein for the detection of Influenza A or B.

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Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circle with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized image of a human figure with three lines representing the body and head. The figure is facing to the right.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

DEC 2 0 1999

Mr. Luann Ochs Regulatory Program Manager Roche Diagnostics Corporation 9115 Hague Road Indianapolis. Indiana 46250-0457

Re: K993048 Trade Name: Roche Diagnostics Influenza A/B Rapid Test Regulatory Class: I Product Code: GNX Dated: November 9, 1999 Received: November 10, 1999

Dear Mr. Ochs:

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 Butman

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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510(k) Number (if known): Device Name: Roche Diagnostics Influenza A/B Rapid Test Indications for Use:

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Woody Dubois

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K993048

Prescription Use (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.