The ViraZyme® Influenza ID test is a direct specimen test indicated for use in the qualitative detection of both influenza types A and B virus from throat swab specimens. The ViraZyme® Influenza ID test may be used when a patient is suspected of having symptoms of an influenza-like illness. These symptoms can include, but are not limited to the following: fever of 38.5℃, sore throat, headache, myalgia, rhinitis, vomiting, chills, malaise, and cough. A positive ViraZyme® result would indicate the presence of influenza type A or B virus. A negative result is considered presumptive and should be confirmed by culture. The ViraZyme® Influenza ID test does not detect influenza C, and is indicated for in Vitro Diagnostic Use only.

Device Description

The ViraZyme® Influenza ID Test for Influenza Types A and B Viruses is an endogenous viralencoded enzyme assay (EVEA) and is intended for use in the qualitative determination of influenza types A and B from throat swab specimens. The ViraZyme® Influenza ID Test is not intended for the detection of influenza C.

Influenza types A and B virus possess surface glycoproteins with neuraminidase activity, that hydrolyze substrates which contain alpha-ketosidically linked N-acetylneuraminic acid (Neu5Ac). A modified Neu5Ac molecule has been synthesized and coupled to a chromogen to produce the neuraminidase substrate. In the presence of influenza types A and B virus the chromogenic substrate is then cleaved by the action of viral neuraminidase, releasing a free chromogen. This free chromogen precipitates to produce a blue color. The blue precipitate is then concentrated and collected from the reaction mixture onto a filter device.

AI/ML Overview

ViraZyme® Influenza ID Test: Acceptance Criteria and Performance

1. Acceptance Criteria and Reported Device Performance

The provided document does not explicitly state pre-defined acceptance criteria. However, it presents the clinical performance of the ViraZyme® Influenza ID Test against a reference method. Based on the reported results, we can infer the achieved performance metrics.

Performance Metric	Acceptance Criteria (Inferred)	Reported Device Performance
Overall
Sensitivity (Influenza A & B)	Adequate for screening/diagnostic aid	62.2% (51/82)
Specificity (Influenza A & B)	High	98.7% (74/75)
Influenza A
Sensitivity (Influenza A)	Adequate for screening/diagnostic aid	65.3% (32/49)
Specificity (Influenza A)	High	99.1% (107/108)
Influenza B
Sensitivity (Influenza B)	Adequate for screening/diagnostic aid	57.6% (19/33)
Specificity (Influenza B)	High	99.2% (123/124)
Reproducibility	100% correlation	100% correlation

Note: The inferred "Acceptance Criteria" are based on the typical expectations for in vitro diagnostic tests used as screening tools, where high specificity is often prioritized to minimize false positives, and sensitivity is acceptable for a screening test that would be confirmed by a more definitive method. The 100% reproducibility is explicitly stated as demonstrating adequate performance across different environments.

2. Sample Size for the Test Set and Data Provenance

Sample Size for Test Set: 157 throat swab specimens.
Data Provenance: The data was collected from field sites across the United States during the 1995-96 influenza season (November 11, 1995 to March 29, 1996). This was a prospective study, as specimens were collected specifically for this evaluation.

3. Number of Experts Used to Establish Ground Truth and Qualifications

The document does not explicitly state the number of experts or their specific qualifications (e.g., number of years of experience). However, it mentions that the reference method involved "viral isolation and culture confirmation with monoclonal antibodies" which is a laboratory-based gold standard. This process would typically be performed and interpreted by trained laboratory personnel, likely microbiologists or virologists, with expertise in viral culture and identification.

4. Adjudication Method

The document does not describe an explicit adjudication method (e.g., 2+1, 3+1). The ground truth was established by a single reference method: viral isolation and culture confirmation with monoclonal antibodies. There is no indication of multiple expert readings or a consensus process for the reference method.

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

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. The study focuses solely on the standalone performance of the ViraZyme® Influenza ID Test compared to a laboratory reference method. There is no mention of human readers' performance with or without AI assistance, as this is an in-vitro diagnostic test, not an AI-assisted diagnostic tool for human interpretation.

6. Standalone Performance

Yes, a standalone performance study was done. The entire clinical evaluation described in the document assesses the ViraZyme® Influenza ID Test's performance (algorithm/assay only, without human-in-the-loop interpretation impacting the result) against the reference method. The reported sensitivity and specificity values are for the device's standalone performance.

7. Type of Ground Truth Used

The type of ground truth used was viral isolation and culture confirmation with monoclonal antibodies. This is considered a highly reliable and definitive method for identifying influenza viruses.

8. Sample Size for the Training Set

The document does not provide any information regarding a distinct training set sample size. The clinical study described in the document appears to be solely for validation/testing purposes. It's possible that the device's development involved internal studies or smaller pilot data not mentioned in this summary, but no details are provided.

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

As no information regarding a separate training set is provided, there is no information on how its ground truth would have been established.

Summary

{0}------------------------------------------------

KY71494

ViraZyme® Influenza ID Test for Influenza Types A and B Virus Appendix D - Safety and Effectiveness Summary

SEP 1 0 1997

Appendix D Safety and Effectiveness Summary for ViraZyme® Influenza ID Test for Influenza Types A and B Virus

This information is provided as a summary of the safety and effectiveness of the ZymeTx, ViraZyme® Influenza ID Test for Influenza Types A and B Viruses. For more detailed information please refer to the product package insert.

PERFORMANCE CHARACTERISTICS

Clinical studies were performed using the ViraZyme® Influenza ID Test for Influenza Types A and B Virus at seven separate locations throughout the United States. A portion of these sites conducted studies comparing the ViraZyme® Influenza ID Test results obtained from standard culture confirmation with monoclonal antibodies. All seven of the sites conducted reproducibility studies to determine that the ViraZyme® Influenza ID Test would perform similarly in various physician offices, laboratories, clinics and hospital settings.

A total of 157 throat swab specimens were collected from field sites during the 1995-96 influenza season between November 11, 1995 to March 29, 1996. Each of these specimens were tested by the ViraZyme® Influenza ID Test and tested by the reference method of viral isolation and culture confirmation with monoclonal antibodies. Six physicians and their nurses and technicians, from two separate physician offices in a Southwest region participated in the collection and testing of ViraZyme® Test. Duplicate throat swab specimens were collected and transported by courier to a Southwestern viral testing laboratory for the culture portion of this testing.

Of the 157 specimens collected and tested, a total of 49/157 were positive by the viral isolation and culture confirmation method for influenza A (31%); 33/157 were positive by the viral isolation and culture confirmation method for influenza B (21%); 1/157 were positive by the viral isolation and culture confirmation method for parainfluenza type 1 (1%); 1/157 were positive by the viral isolation and culture confirmation method for adenovirus (1%); and 73/157 were negative by the viral isolation and culture confirmation method for the respiratory viruses (46%). No parainfluenza type 2 or 3, or respiratory syncytial virus were detected by the viral isolation and culture confirmation method during this study.

{1}------------------------------------------------

SENSITIVITY AND SPECIFICITY RESULTS Detection of Influenza Types A and B

The ViraZyme® Influenza ID Test detected 51/82 (62.2%) of culture confirmed positives for influenza type A and type B from throat swab specimens. The ViraZyme® Influenza ID Test properly identified 74/75 (98.7%) of culture confirmed negatives for influenza types A and B virus from throat swab specimens.

Detection of Influenza Types A

The ViraZyme® Influenza ID Test detected 32/49 (65.3%) of culture confirmed positives for influenza type A and type B from throat swab specimens. The ViraZyme® Influenza ID Test properly identified 107/108 (99.1%) of culture confirmed negatives for influenza type A virus from throat swab specimens.

Detection of Influenza Types B

The ViraZyme® Influenza ID Test detected 19/33 (57.6%) of culture confirmed positives for influenza type B from throat swab specimens. The ViraZyme® Influenza ID Test properly identified 123/124 (99.2%) of culture confirmed negatives for influenza type B virus from throat swab specimens.

VIRAZYME® INFLUENZA ID TEST RESPRODUCIBILITY

There was 100% correlation of results during the reproducibility testing of the ViraZyme® Influenza ID Test at seven physician offices, clinics, research laboratories and hospital settings conducted during the 1996-97 influenza season. We believe that this adequately demonstrates that the ViraZyme® Influenza ID Test will perform similarly in various test environment settings in the hands of various personnel.

TECHNICAL INFORMATION

For technical information and comments regarding this product, you may contact the ViraZyme® Influenza ID Product Manager at (405) 271-1314.

This Safety and Effectiveness Summary has been provided as a part of the 510(k) notification for the ViraZyme® Influenza ID Test for Influenza Types A and B Virus

Cray D. Shimazaki Ph.D

Craig D. Shimasaki, Ph.D. Vice President of Research

4/23/91

Date

{2}------------------------------------------------

Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with three human profiles incorporated into its design. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged around the eagle in a circular fashion.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

SEP 1 0 1997

Craig D. Shimasaki, Ph.D. ZymeTx, Inc. 800 Research Parkway * Suite 100 Oklahoma City, OK 73104

SEP 10 1997

Re: K971494

Trade Name: VstatFlu™ Test for Influenza Types A and B Virus Regulatory Class: I Product Code: GNX Dated: July 18, 1997 Received: July 21, 1997

Dear Dr. Shimasaki:

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 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 QS 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.

{3}------------------------------------------------

Page 2

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 (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

{4}------------------------------------------------

1 of of a 1 Page:

510(k) Number (if known): ____________________________________________________________________________________________________________________________________________________

Device Name: ZstatFlu ™ Test for Influenza Types A and B Viruses

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)
OR Over-The-Counter Use:

(Optional Format 1-2-96)
(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number	K971494

Regulation Number and Section

§ 866.3330 Influenza virus serological reagents.

(a)
Identification. Influenza virus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to influenza in serum. The identification aids in the diagnosis of influenza (flu) and provides epidemiological information on influenza. Influenza is an acute respiratory tract disease, which is often epidemic.(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 the limitations in § 866.9.