The ZstatFlu® Test for Influenza Type A and B Viruses is an endogenous viral-encoded enzyme assay (EVEA) and is intended for use in the qualitative determination of influenza types A and B from throat swab specimens. The ZstatFlu® Test for Influenza Type A and B Viruses is not intended for the detection of influenza C. This test is indicated for the direct testing of patients presenting with influenza-like illnesses.

Device Description

The Improved ZstatFlu® Test for Influenza Types A and B Virus 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 Improved ZstatFlu® Test for Influenza Types A and B Virus 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-acetyIneuraminic 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

Here's a breakdown of the acceptance criteria and study details for the ZstatFlu® Test for Influenza Types A and B Virus, based on the provided document:

Acceptance Criteria and Device Performance

The document does not explicitly state pre-defined "acceptance criteria" with numerical thresholds for sensitivity and specificity that the device was required to meet. Instead, it reports the observed performance characteristics from the clinical study. The FDA's letter of clearance (K982429) confirms that the device was found substantially equivalent to legally marketed predicate devices, implying that its performance was deemed acceptable for its intended use.

Here are the reported performance characteristics:

Performance Metric	Reported Device Performance (%)
Detection of Influenza Types A and B
Sensitivity (Positive Agreement)	62.2% (51/82)
Specificity (Negative Agreement)	98.7% (74/75)
Detection of Influenza Type A
Sensitivity (Positive Agreement)	65.3% (32/49)
Specificity (Negative Agreement)	99.1% (107/108)
Detection of Influenza Type B
Sensitivity (Positive Agreement)	57.6% (19/33)
Specificity (Negative Agreement)	99.2% (123/124)
Reproducibility	100% correlation

Study Details

Sample Size used for the test set and the data provenance:
- Sample Size: 157 throat swab specimens.
- Data Provenance:
  - Country of Origin: United States.
  - Retrospective or Prospective: The specimens were collected from field sites during the 1995-96 influenza season (November 11, 1995 to March 29, 1996) and then tested. This indicates a prospective collection for the purpose of the study.
  - Collection Sites: Seven separate locations throughout the United States, including physician offices, laboratories, clinics, and hospital settings. Specifically, six physicians and their nurses and technicians from two physician offices in a Southwest region participated in collection and testing.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The document does not explicitly state the number of individual experts or their specific qualifications (e.g., radiologist with X years of experience).
- However, it mentions "the reference method of viral isolation and culture confirmation with monoclonal antibodies" conducted at a "Southwestern viral testing laboratory." This implies that trained laboratory personnel and virologists were involved in establishing the ground truth, but specific numbers and detailed qualifications are not provided.
Adjudication method for the test set:
- The document does not mention an adjudication method (like 2+1 or 3+1) for the interpretation of the reference method results. It simply states the reference method was "viral isolation and culture confirmation with monoclonal antibodies."
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, a multi-reader multi-case (MRMC) comparative effectiveness study was not conducted. This is an in vitro diagnostic device (IVD) for direct detection of viruses, and the study design focuses on comparing the device's performance against a laboratory reference standard, not human reader performance.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, the performance data presented is for the device in a standalone manner (algorithm only, without human-in-the-loop performance in terms of interpretation, other than operating the test according to instructions). The test is an "endogenous viral-encoded enzyme assay (EVEA)" that produces a visible color change, which is then presumably read and interpreted by the user of the device. The reproducibility studies, however, did assess variations across different users and settings.
The type of ground truth used:
- The ground truth used was laboratory reference standard: viral isolation and culture confirmation with monoclonal antibodies.
The sample size for the training set:
- The document does not specify a separate training set or its sample size. The ZstatFlu® test is described as an "endogenous viral-encoded enzyme assay (EVEA)" based on a chemical reaction, not a machine learning algorithm that typically requires a training set. Manufacturers of such diagnostic kits typically validate the assay's performance characteristics through analytical and clinical studies, rather than "training" an AI model.
How the ground truth for the training set was established:
- Not applicable, as there is no mention of a traditional "training set" for a machine learning model.

Summary

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Image /page/0/Picture/1 description: The image shows the logo for ZymeTx, Inc. The logo features a stylized graphic to the left of the company name. Below the company name is the address "800 Research Parkway, Suite 100, Oklahoma City, OK 73104".

K982429

Suite 100 • Oklahoma City, OK 73104-3600 • 405 / 271-1314 • Fax 405 / 271-1944 • www.zymetx.com

Appendix C Safety and Effectiveness Summary for Improved ZstatFlu® Test for Influenza Types A and B Virus 510(k) Summary as Required by Section 807.92(c) (Prepared July 10, 1998)

Submtter's Name:	Craig D. Shimasaki, Ph.D.Vice President, ResearchZymeTx, Inc.800 Research Parkway, Suite 100Oklahoma City, OK 73104Phone: 405/271-1314Fax: 405/271-1944	Trade Name:	ZstatFlu® Test for InfluenzaTypes A and B Virus
Contact Person:	Craig D. Shimasaki, Ph.D.Vice President, Research	Common Name:	Diagnostic Test for DirectDetection of Influenza TypesA and B Virus
		Classificaiton Name:	Influenza virus serologicalregents per 807.87(c)

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

Influenza types A and B virus possess surface glycoproteins with neuraminidase activity, that hydrolyze substrates which contain alpha-ketosidically linked N-acetyIneuraminic 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.

PERFORMANCE CHARACTERISTICS

Clinical studies were performed using the Improved ZstatFlu® 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 Improved ZstatFlu® Test for Influenza Types and A and B Virus results to results obtained from standard culture confirmation with monoclonal antibodies. All seven of the sites conducted reproducibility studies to determine that the

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Improved ZstatFlu® Test for Influenza Types A and B Virus 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 Improved ZstatFlu® Test for Influenza Types A and B Virus 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 Improved ZstatFlu® Test for Influenza Types A and B Virus. 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.

SENSITIVITY AND SPECIFICITY RESULTS

Detection of Influenza Types A and B

The Improved ZstatFlu® Test for Influenza Types A and B Virus detected 51/82 (62.2%) of culture confirmed positives for influenza type A and type B from throat swab specimens. The Improved ZstatFlu® Test for Influenza Types A and B Virus 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 Improved ZstatFlu® Test for Influenza Types A and B Virus detected 32/49 (65.3%) of culture confirmed positives for influenza type A and type B from throat swab specimens. The Improved ZstatFlu® Test for Influenza Types A and B Virus 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 Improved ZstatFlu® Test for Influenza Types A and B Virus detected 19/33 (57.6%) of culture confirmed positives for influenza type B from throat swab specimens. The Improved

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ZstatFlu® Test for Influenza Types A and B Virus properly identified 123/124 (99.2%) of culture confirmed negatives for influenza type B virus from throat swab specimens.

IMPROVED ZSTATFLU® TEST FOR INFLUENZA TYPES A AND B VIRUS REPRODUCIBILITY

There was 100% correlation of results during the reproducibility testing of the Improved ZstatFlu® Test for Influenza Types A and B 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 Improved ZstatFlu® Test for Influenza Types A and B 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 Improved ZstatFlu® Test for Influenza Types A and B Virus Product Manager at (405) 271-1314.

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

Craig D. Summoch Ph.D.

Shimasaki, Ph.D Vice President of Research

7/10/98

Date

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Image /page/3/Picture/2 description: The image shows the logo for the Department of Health & Human Services - USA. The logo is circular and contains the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. In the center of the logo is a stylized image of an eagle.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

AUG 25 1998

Craig D. Shimasaki. Ph.D. Vice President of Research ZymeTx, Inc. 800 Research Parkway, Suite 100 Oklahoma City, OK 73104-3600

Re: K982429

Trade Name: (Improved) ZstatFlu® Test for Influenza Types A and B Virus Regulatory Class: I Product Code: GNX Dated: July 10, 1998 Received: July 13, 1998

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 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 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.

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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 Gutman

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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INDICATIONS FOR USE STATEMENT

510(k) Number: 1098 2429

Device Name: (Improved) ZstatFlu® Test for Influenza Types A and B Virus

Indications for Use:

(Please do not write below this line - continue on another page if needed)

Concurrence of CDRH, Office of Device Valuation (ODE)

Division Sign-Off	Woody Jufolo
Division of Clinical Laboratory Devices
510(k) Number	K982429

Prescription Use	X	OR	Over-The-Counter Use
------------------	----------------------------------------	----	----------------------

(Per 21 CFR 801.109)

(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.