K Number

Device Name

WEST NILE VIRUS ELISA IGG, MODEL EL0300G

Manufacturer

FOCUS TECHNOLOGIES, INC.

Date Cleared

2003-10-22

(119 days)

Product Code

NOP

Regulation Number

866.3940

Intended Use

The Focus Technologies West Nile Virus ELISA IgG is intended for qualitatively detecting IgG antibodies to West Nile virus in human serum. In conjunction with the Focus Technologies West Nile Virus IgM Capture ELISA, the test is indicated for testing persons having symptoms of meningioencephalitis, as an aid in the presumptive laboratory diagnosis of West Nile virus infection. Positive results must be confirmed by neutralization test, or by using the current CDC guidelines for diagnosing West Nile encephalitis. This test is not intended for self-testing, and this test is not FDA cleared nor approved for testing blood or plasma donors. Assay performance characteristics have not been established for automated instruments.

Device Description

Indirect Enzyme-linked immunosorbent assay for qualitatively detecting human serum IgG antibodies to West Nile virus.

More Information

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Third Party Reviewed

Expedited Review

Predicate Devices

K913617, K993724

Reference Devices

CDC West Nile Virus IgG ELISA, West Nile Virus Plaque Reduction Neutralization Test

AI/ML (Artificial Intelligence / Machine Learning)

No
The document describes a standard ELISA assay for detecting antibodies and does not mention any AI or ML components. The performance studies are based on traditional statistical analysis of assay results.

Therapeutic

No.
This device is an in vitro diagnostic (IVD) test intended for the qualitative detection of antibodies to West Nile virus, which serves as an aid in diagnosis, not a therapeutic intervention.

Diagnostic

Yes

Explanation: The device is intended for "qualitatively detecting IgG antibodies to West Nile virus in human serum" and is indicated "as an aid in the presumptive laboratory diagnosis of West Nile virus infection." This clearly describes a diagnostic purpose.

SaMD (Software as a Medical Device)

The device description explicitly states it is an "Indirect Enzyme-linked immunosorbent assay," which is a laboratory test method involving physical reagents and procedures, not solely software.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

Intended Use: The "Intended Use / Indications for Use" section explicitly states that the device is "intended for qualitatively detecting IgG antibodies to West Nile virus in human serum." This is a classic description of an in vitro diagnostic test, as it is used to examine a sample taken from the human body (serum) to provide information about a disease state (presence of West Nile virus antibodies).
Device Description: The "Device Description" further clarifies that it is an "Indirect Enzyme-linked immunosorbent assay for qualitatively detecting human serum IgG antibodies to West Nile virus." ELISA is a common technique used in IVD tests.
Sample Type: The device uses "human serum," which is a biological sample taken from the body.
Purpose: The test is used "as an aid in the presumptive laboratory diagnosis of West Nile virus infection," which is a diagnostic purpose.
Care Setting: While not for self-testing, the intended user is implied to be in a clinical laboratory setting, which is where IVD tests are typically performed.

The information provided aligns perfectly with the definition and characteristics of an In Vitro Diagnostic device.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

Product codes

NOP

Device Description

Indirect Enzyme-linked immunosorbent assay for qualitatively detecting human serum IgG antibodies to West Nile virus.

Mentions image processing

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Mentions AI, DNN, or ML

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Input Imaging Modality

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Anatomical Site

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Indicated Patient Age Range

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Intended User / Care Setting

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Description of the training set, sample size, data source, and annotation protocol

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Description of the test set, sample size, data source, and annotation protocol

Study Site 1: Focus Reactivity with Encephalitis/Meningitis Patients (n = 300)

Sample Size: 300
Data Source: Retrospective sera from encephalitis/meningitis patients, sequentially submitted to a state department of health laboratory in the northeastern U.S., archived, and masked.
Annotation Protocol: Reference methods were CDC WNV IgG Capture ELISA, and plaque reduction neutralization test (PRNT) for West Nile virus. Patients were classified as confirmed positive WNV encephalitis if they had meningioencephalitis symptoms, were CDC WNV IgG ELISA positive, and WNV PRNT positive. Presumptive assay results were based on CDC WNV IgG ELISA.

Study Site 2: Focus Reactivity with WNV PRNT Positives (n = 75)

Sample Size: 75
Data Source: ۷۵ retrospective sera screened positive by Focus with a West Nile virus native antigen ELISA, and confirmed West Nile positive by plaque reduction neutralization test (PRNT). Sera were sequentially submitted to a clinical laboratory in the mid-western U.S., archived.
Annotation Protocol: WNV PRNT positive.

Study Site 3: Focus Reactivity with West Nile IFA Negatives (n=157)

Sample Size: 157
Data Source: Reactive West Nile IFA negative samples from a clinical laboratory in the southwestern U.S.
Annotation Protocol: West Nile IFA negative.

Study Site 4: Focus Reactivity with Suspected Encephalitis/Meningitis Patients (n = 50)

Sample Size: 50
Data Source: Retrospective and masked sera from patients suspected of encephalitis/meningitis, provided by a U.S. federal government laboratory.
Annotation Protocol: One sample confirmed positive by West Nile PRNT. Other 49 presumptively negative (CDC ELISA) for arboviruses present in North America (LAC, EEE, SLE and WNV).

Study Site 4: Focus Reactivity with Non-Flavivirus Test Samples (n = 476)

Sample Size: 476
Data Source: Prospectively collected samples from North America during August 2003, submitted to a clinical laboratory in Southern California for non-flavivirus tests (e.g., test for other infectious diseases).
Annotation Protocol: Positive samples tested with a CDC West Nile IgG ELISA.

Focus Cross-reactivity

Sample Size: 75
Data Source: Sera sero-positive to other potentially cross-reactive pathogens. DOH (State Department of Health in northeastern U.S., Study Site 1) tested SLE positives, Focus (Study Site 4) tested other sera. Sera were archived and masked.
Annotation Protocol: Serological status to other pathogens (Dengue, Japanese encephalitis, St. Louis encephalitis, Yellow fever, Alphavirus, Bunyavirus, Herpes simplex virus type 1, Epstein-Barr virus, Cytomegalovirus, Echovirus/Poliovirus, Borrelia burgdorferi).

Summary of Performance Studies

Performance Characteristics:

Study Site 1: Focus Reactivity with Encephalitis/Meningitis Patients (n = 300)

Study Type: Clinical Performance Study
Sample Size: 300
Key Results: The Focus IgG ELISA was positive with 97.3% (36/37) of confirmed positive WNV encephalitis patients (including 1 Focus equivocal calculated as negative). It was positive with 100% (4/4) of presumed positive WNV encephalitis patients and with the one dengue positive patient. It was negative with 99.0% (203/205) of presumed negative patients (including 1 Focus equivocal calculated as positive).
Clinical sensitivity (encephalitis or meningitis symptoms, CDC WNV IgG ELISA positive and WNV PRNT positive): 97.3% (36/37) (95% CI: 85.8-99.9%)
Positive agreement with presumptive CDC WNV IgG ELISA: 100% (5/5) (95% CI: 47.8-100%)
Negative agreement with presumptive CDC WNV IgG ELISA negative: 99.0% (203/205) (95% CI: 96.5-99.9%)

Study Site 2: Focus Reactivity with WNV PRNT Positives (n = 75)

Study Type: Clinical Performance Study
Sample Size: 75
Key Results: The Focus IgG ELISA was positive with 36.0% (27/75) of the 75 PRNT positives (calculating 4 equivocals as negative), equivocal with four samples, and negative with 44 samples.
Serological sensitivity (WNV PRNT positive): 36.0% (27/75) (95% CI: 25.2-92.3%)

Study Site 3: Focus Reactivity with West Nile IFA Negatives (n=157)

Study Type: Clinical Performance Study
Sample Size: 157
Key Results: The Focus IgG ELISA was 96.8% (152/157) negative with WNV IgG IFA negative samples (including two equivocals calculated as positive), and positive with three samples.
Negative agreement with presumptive WNV IFA: 95.6% (152/157) (95% CI: 91.1-98.2%)

Study Site 4: Focus Reactivity with Suspected Encephalitis/Meningitis Patients (n = 50)

Study Type: Clinical Performance Study
Sample Size: 50
Key Results: The Focus IgG ELISA was negative with 95.6% (47/49) of the WNV negative samples, and positive with the one positive confirmed by West Nile PRNT.
Serological sensitivity (CDC IgG ELISA positive and WNV PRNT positive): 100% (1/1) (95% CI: NA)
Negative agreement with presumptive CDC IgG ELISA: 95.9% (47/49) (95% CI: 86.0-99.5%)

Study Site 4: Focus Reactivity with Non-Flavivirus Test Samples (n = 476)

Study Type: Clinical Performance Study
Sample Size: 476
Key Results: The Focus West Nile ELISA IgG was negative with 96.8% (426/440) of the CDC ELISA negative samples (including 14 Focus equivocals calculated as positive), and was positive with 100% (21/21) of the CDC ELISA positive samples.
Positive agreement with presumptive CDC IgG ELISA: 100% (21/21) (95% CI: 83.9-100%)
Negative agreement with presumptive CDC IgG ELISA: 96.8% (426/440) (95% CI: 94.7-98.3%)

Focus Cross-reactivity

Study Type: Cross-reactivity Study
Sample Size: 75 (total across populations)
Key Results: Demonstrated varying degrees of cross-reactivity with other pathogens, particularly high positivity for Dengue virus (95.0%) and St. Louis encephalitis virus (57.1%). Lower rates for Japanese encephalitis virus, Yellow fever virus, Alphavirus, Bunyavirus, Herpes simplex virus type 1, Epstein-Barr virus, Cytomegalovirus, Echovirus/Poliovirus, and Borrelia burgdorferi.

Focus Sample Freeze-Thaw Study

Study Type: Stability Study
Sample Size: 8 sera (5 positive, 3 negative)
Key Results: No changes in interpretation were observed in any of the sera after up to 5 repeated freeze-thaw cycles. Positive samples in IgM ELISA trended slightly towards increasing indices, while negative samples in IgG ELISA did not appear to change indices.

Focus Reproducibility

Study Type: Reproducibility Study (Inter-lot, Inter/Intra-assay, Inter-laboratory)
Sample Size: Varies by study (e.g., 5 samples for inter-lot, 7 for inter/intra-assay and inter-laboratory)
Key Results:
- Inter- & Intra-assay: Intra-assay %CV ranged from 1.0% to 21.2%; Inter-assay %CV ranged from 16.2% to 21.3%.
- Inter-lot: Index %CV ranged from 4.1% to 13.1%.
- Inter-Lab: Index %CV ranged from 11.0% to 22.3%.

Key Metrics

Clinical sensitivity (encephalitis or meningitis symptoms, CDC WNV IgG ELISA positive and WNV PRNT positive): 97.3% (36/37) (95% CI: 85.8-99.9%)
Positive agreement with presumptive CDC WNV IgG ELISA: 100% (5/5) (95% CI: 47.8-100%)
Negative agreement with presumptive CDC WNV IgG ELISA negative: 99.0% (203/205) (95% CI: 96.5-99.9%)
Serological sensitivity (WNV PRNT positive): 36.0% (27/75) (95% CI: 25.2-92.3%)
Negative agreement with presumptive WNV IFA: 95.6% (152/157) (95% CI: 91.1-98.2%)
Serological sensitivity (CDC IgG ELISA positive and WNV PRNT positive): 100% (1/1) (95% CI: NA)
Negative agreement with presumptive CDC IgG ELISA: 95.9% (47/49) (95% CI: 86.0-99.5%)
Positive agreement with presumptive CDC IgG ELISA: 100% (21/21) (95% CI: 83.9-100%)
Negative agreement with presumptive CDC IgG ELISA: 96.8% (426/440) (95% CI: 94.7-98.3%)

Cross-reactivity % Positive:

Dengue virus (secondary infections): 95.0% (19/20) (95% CI: 75.1-99.9%)
Japanese encephalitis virus: 30.0% (6/20) (95% CI: 11.9-54.3%)
St. Louis encephalitis virus: 57.1% (12/21) (95% CI: 34.0-78.2%)
Yellow fever virus: 45.0% (9/20) (95% CI: 23.1-68.5%)
Alphavirus (Sindbis & Eastern equine viruses): 11.8% (2/17) (95% CI: 0.1-36.4%)
Bunyavirus (Jamestown Canyon & La Crosse): 20.0% (3/15) (95% CI: 4.3-48.1%)
Herpes simplex virus type 1: 8.3% (5/60) (95% CI: 2.8-18.4%)
Epstein-Barr virus: 8.3% (1/12) (95% CI: 0.2-38.5%)
Cytomegalovirus: 20.0% (4/20) (95% CI: 5.7-43.7%)
Echovirus/Poliovirus: 10.0% (2/20) (95% CI: 1.2-31.7%)
Borrelia burgdorferi (Lyme disease): 15.0% (3/20) (95% CI: 3.2-37.9%)

Predicate Device(s)

Focus Technologies Arbovirus IFA IgG (K913617), Focus Technologies HSV-2 ELISA (K993724), CDC West Nile Virus IgG ELISA, West Nile Virus Plaque Reduction Neutralization Test

Reference Device(s)

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information

Not Found

Regulation Number and Section

§ 866.3940 West Nile virus serological reagents.

(a)
Identification. West Nile virus serological reagents are devices that consist of antigens and antisera for the detection of anti-West Nile virus IgM antibodies, in human serum, from individuals who have signs and symptoms consistent with viral meningitis/encephalitis. The detection aids in the clinical laboratory diagnosis of viral meningitis/encephalitis caused by West Nile virus.(b)
Classification. Class II (special controls). The special control is FDA's guidance entitled “Class II Special Controls Guidance Document: Serological Reagents for the Laboratory Diagnosis of West Nile Virus.” See § 866.1(e) for the availability of this guidance document.

Summary

OCT 2 2 2003

Image /page/0/Picture/1 description: The image shows the logo for Focus Technologies. The logo consists of the word "FOCUS" in a bold, sans-serif font, with two crescent moon shapes forming the letter "O". Below the word "FOCUS" is the word "technologies" in a smaller, sans-serif font. The logo is black and white.

031953

| Applicant | Focus Technologies, Inc.
10703 Progress Way
Cypress, California 90630
USA |
|-----------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Establishment
Registration No. | 2023365 |
| Contact Person | Michael J. Wagner, Esq.
tel (714) 220-1900
fax (714) 995-6921
mwagner@focustechnologies.com |
| Summary Date | October 17, 2003 |
| Proprietary Name | West Nile Virus ELISA IgG |
| Generic Name | West Nile Virus ELISA IgG |
| Classification | West Nile Virus Serological Reagents
21 CFR §866.3940
Class II |
| Predicate Device | Focus Technologies Arbovirus IFA IgG (K913617)
Focus Technologies HSV-2 ELISA (K993724)
CDC West Nile Virus IgG ELISA
West Nile Virus Plaque Reduction Neutralization Test |

Device Description

Indirect Enzyme-linked immunosorbent assay for qualitatively detecting human serum IgG antibodies to West Nile virus.

Intended Use

Test Principle

In the Focus Technologies West Nile Virus ELISA IgG assay, the polystyrene microwells are coated with recombinant West Nile virus antigen. Diluted serum samples and controls are incubated in the wells to allow anti-WNV IgG antibody (if present in the sample) to react with the antigen. Nonspecific reactants are removed by washing and peroxidaseconjugated anti-human IgG is added that reacts with human IgG bound to the antigen. Excess conjugate is removed by washing. Enzyme substrate and chromogen are added, and the color is allowed to develop. After adding the Stop Reagent, the resultant color change is quantified by a spectrophotometric reading of optical density readings are compared with reference cut-off OD readings to determine results.

K031953 510(k) Summary of Safety and Effectiveness West Nile Virus ELISA IgG Catalog No. EL0300G Prepared October 17, 2003

Expected Values

The prevalence of West Nile antibodies varies depending age, geographic location, testing method used, and other factors. A community based serosurvey for West Nile infection conducted in New York in 2000 found that 0.2% (5/2433) of persons tested overall had antibodies indicating recent West Nile infection, and that 1.1% (2/176) of persons reporting a recent headache and fever had antibodies indicating a recent West Nile infection. Two serosurveys conducted in New York City (NYC) in 1999 and 2000 showed that approximately 1 in 150 infections ( Trade/Device Name: West Nile Virus ELISA IgG Regulation Number: 21 CFR 866.3940 Regulation Name: West Nile Virus Serological Reagents Regulatory Class: Class II Product Code: NOP Dated: October 17, 2003 Received: October 20, 2003

Dear Mr. Wagner:

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 Mav 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. Iisting 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 (OS) regulation (21 CFR Part 820).

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

510(k) Number (if known): K031953

Device Name:

West Nile Virus ELISA IgG

The Focus Technologies West Nile Virus ELISA IgG is intended Indications for Use: for qualitatively detecting IgG antibodies to West Nile virus in human serum. In conjunction with the Focus Technologies West Nile Virus IgM Capture ELISA, the test is indicated for testing persons having symptoms of meningioencephalitis, as an aid in the presumptive laboratory diagnosis of West Nile virus infection. Positive results must be confirmed by neutralization test, or by using the current CDC guidelines for diagnosing West Nile encephalitis. This test is not intended for self-testing, and this test is not FDA cleared nor approved for testing blood or plasma donors. Assay performance characteristics have not been established for automated instruments.

(PLEASE DO NOT WRITE BELOW THIS LINE CONTINUE ON ANOTHER PAGE IF NEEDED) Concurrence of CDRH, Office of Device Evaluation (ODE)

Soyattyns 10/21/03
Division Sign-Off

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

(Optional Format 3-10-98)

510(k)K031953

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