The Viral Capsid Antigen (VCA) IgG kit is an Enzyme-Linked Immunosorbent Assay (ELISA) for the qualitative determination of IgG antibodies in human serum to VCA antigen. The Clark anti-VCA IgG assay may be used in conjunction with other Epstein-Barr serologies (EA-D IgG, VCA IgM, EBNA-1 IgG, EBNA-1 IgM and heterophile) as an aid in the diagnosis of infectious mononucleosis in a adult population.

Device Description

The Epstein-Barr Viral Capsid Antigen (VCA) IgG kit is an Enzyme-Linked Immunosorbent Assay (ELISA) for the qualitative determination of IgG antibodies in human serum to VCA antigen. The Clark anti-VCA IgG assay may be used in conjunction with other Epstein-Barr serologies (EA-D IgG, VCA IgM, EBNA-1 IgG, EBNA-1 IgM and heterophile) as an aid in the diagnosis of infectious mononucleosis. For In Vitro Diagnostic Use Only. The VCA IgG ELISA test is an enzyme linked immunosorbent assay to detect IgG antibodies to Epstein-Barr Viral Capsid Antigen. Purified recombinant VCA antigen is attached to a solid phase microtiter well. Diluted test sera is added to each well. If the antibodies are present that recognize the antigen, they will bind to the antigen in the well. After incubation the wells are washed to remove unbound antibody. An enzyme labeled anti-human IgG is added to each well. If antibody is present it will bind to the antibody attached to the antigen on the well. After incubation the wells are washed to remove unbound conjugate. A substrate solution is added to each well. If enzyme is present the substrate will undergo a color change. After an incubation period the reaction is stopped and the color intensity is measured photometrically, producing an indirect measurement of specific antibody in the patient specimen.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study details for the VCA IgG ELISA Test Kit, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria for the different performance metrics. However, we can infer the reported performance as the outcome of the evaluation.

Performance Characteristic	Reported Device Performance
Sensitivity
Relative Sensitivity (Acute)	58.8% (95% CI: 41.9%-75.7%)
Relative Sensitivity (Seropositive)	95.0% (95% CI: 90.5%-99.4%)
Specificity
Relative Specificity (Seronegative)	100% (95% CI: 89.0%-100%)
Agreement
Relative Agreement	87.5% (95% CI: 82.3%-92.7%)
Precision	(Coefficient of Variation (CV)
Serum 1	7.80%
Serum 2	11.33%
Serum 3	8.33%
Serum 4	13.32%
Serum 5	23.48%
Serum 6	26.16%
HP (High Positive)	9.19%
Cal (Calibrator)	5.99%
LP (Low Positive)	13.92%
NC (Negative Control)	105.88%
Cross-Reactivity	No cross-reactivity observed with Herpes Simplex Virus I & II, Cytomegalovirus, and Varicella Zoster Virus IgG antibodies (all VCA IgG results ≤ 0.61 for these sera, with negative threshold ≤ 0.90).

2. Sample size used for the test set and the data provenance

Sample Size (Sensitivity and Specificity study): 166 selected serum samples.
- 39 samples characterized as Acute
- 99 samples characterized as Seropositive
- 28 samples characterized as Seronegative
Data Provenance: The serums were "tested at a clinical lab." The origin country is not specified, but the context of the submission to the FDA suggests the data is likely from the United States or intended for the US market. The study is retrospective, as the serum samples were "selected" and "characterized" prior to testing with the VCA IgG ELISA kit.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

The ground truth was established by "characteriz[ing]" the serum samples as "seronegative," "acute," or "seropositive" based on other Epstein-Barr virus (EBV) serologies (VCA IgM, EBNA IgG, heterophile antibody).

Number of experts: Not explicitly stated. The characterization appears to be based on the results of other EBV serology tests, rather than direct expert interpretation of the VCA IgG ELISA results themselves. It's implied that clinical laboratory professionals would interpret these other serology results to categorize the samples.
Qualifications of experts: Not specified, but implied to be individuals competent in interpreting EBV serology results, such as clinical laboratory scientists or physicians.

4. Adjudication method for the test set

The document does not describe an adjudication method for the test set. The categorization of serum samples into "acute," "seropositive," and "seronegative" was based on a panel of other EBV serology tests, and then the VCA IgG ELISA test result was compared to this established classification. Equivocal results from the VCA IgG ELISA were not retested or adjudicated; they were simply excluded from the sensitivity and specificity calculations.

5. 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, an MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic (IVD) ELISA test kit, not an AI-powered image analysis or diagnostic tool that involves human "readers" in the context of interpretation. Therefore, a study on human reader improvement with AI assistance is not applicable.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

Yes, a standalone performance study was done. The entire performance characteristic section (sensitivity, specificity, precision, cross-reactivity) evaluates the VCA IgG ELISA device on its own, independent of human interpretation or assistance beyond the standard laboratory procedures for running the assay and reading the photometric results. The "human-in-the-loop" here is the lab technician conducting the test and reading the quantifiable outcome, not interpreting complex images or clinical scenarios that would typically involve an AI algorithm.

7. The type of ground truth used

The ground truth used was "serological characterization" based on a panel of established EBV serology tests (VCA IgM, EBNA IgG, heterophile antibody). This is a form of reference standard test result.

8. The sample size for the training set

Not applicable. The provided text describes a traditional ELISA diagnostic kit. There is no mention of a "training set" as would be used for machine learning or AI models. The development of such a kit typically involves assay optimization and validation during its development, but not in the sense of a machine learning training set.

9. How the ground truth for the training set was established

Not applicable, as there is no training set for this type of device.

Summary

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Jul 22 1998

K980912

. P. i

Summary of Safety and Effectiveness Information VCA IgG ELISA Test Kit

I. Immuno Probe Inc. 1306 Bailes Lane, Suite F Frederick, Maryland 21701 Contact person: William Boteler Telephone: 301-695-7920 Date of preparation: March 2, 1998

II. Description of Device

For In Vitro Diagnostic Use Only.

The VCA IgG ELISA test is an enzyme linked immunosorbent assay to detect IgG antibodies to Epstein-Barr Viral Capsid Antigen. Purified recombinant VCA antigen is attached to a solid phase microtiter well. Diluted test sera is added to each well. If the antibodies are present that recognize the antigen, they will bind to the antigen in the well. After incubation the wells are washed to remove unbound antibody. An enzyme labeled anti-human IgG is added to each well. If antibody is present it will bind to the antibody attached to the antigen on the well. After incubation the wells are washed to remove unbound conjugate. A substrate solution is added to each well. If enzyme is present the substrate will undergo a color change. After an incubation period the reaction is stopped and the color intensity is measured photometrically, producing an indirect measurement of specific antibody in the patient specimen.

III. Predicate Device

The VCA IgG ELISA test is substantially equivalent to EBV serology. Equivalence is demonstrated by the following comparative results:

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Performance Characteristics

1. Sensitivity and Specificity Based on Serum Characterization

One hundred and sixty six selected serum were tested at a clinical lab. The serum from the study were characterized as seronegative ( no serological evidence of past or present EBV infection), acute (VCA IgM and heterophile antibody present, EBNA IgG absent), or seropositive (presence of VCA IgG antibodies and EBNA IgG, no evidence of VCA IgM or heterophile antibody, indicative of past infection). The sensitivity, specificity and agreement of the assay was determined based on this characterization. It was assumed that the VCA IgG response should be negative for seronegative, and positive for acute serum and convalescent serum. The results are summarized in Table 1.

	AcuteVCA IgM+EBNA IgG -Heterophile +	SeropositiveVCA IgG+EBNA IgG+VCA IgM-Heterophile -	SeronegativeVCA IgG-EBNA IgG -VCA IgM -Heterophile -
WampoleVCA IgG	Positive	20	94	0
	Equivocal	5	0	1
	Negative	14	5	27
	Total	39	99	28
Relative Sensitivity (Acute)		= 20/34	= 58.8%	95% Confidence Interval = 41.9%-75.7%
Relative Sensitivity (Seropositive)		= 94/99	= 95.0%	95% Confidence Interval = 90.5%-99.4%
Relative Specificity (Seronegative)		= 27/27	= 100%	95% Confidence Interval = 89.0%-100%
Relative Agreement		= 140/160	= 87.5%	95% Confidence Interval = 82.3%-92.7%

Table 1

Equivocal results were not included in the calculations.

Equivocal results were not retested. They were reported as equivocal.

The 95% confidence intervals were calculated using the normal method.

The Seronegative 95% Confidence Interval was calculated assuming one false positive.

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Six different sera were assayed ten times each on three different assays at three 2. Precision. 2: 1 receision - Bin direction of the assay. The data from this study is presented in Table 2.

Table 2 VCA IgG ELISA Inter-Site Precision Data

n = 60

Serum	X	SD	CV
1	4.37	0.341	7.80%
2	1.80	0.203	11.33%
3	3.47	0.289	8.33%
4	3.31	0.442	13.32%
5	0.35	0.083	23.48%
6	0.28	0.072	26.16%
HP*	7.22	0.663	9.19%
Cal**	4.00	0.239	5.99%
LP*	2.52	0.351	13.92%
NC*	0.05	0.048	105.88%

HP, LP and NC n = 12 ** Cal n = 18

The methods in NCCLS EP5 were utilized for precision

X = Mean ISR parameters. SD = Standard Deviation CV = Coefficient of Variation

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Cross-Reactivity. Serum containing IgG antibody detectable by ELISA to Herpes Simplex Virus I & II, Cytomegalovirus, and Varicella Zoster Virus were assayed. The data summarized in Table 3 indicates that antibodies to these Herpes Viruses do not cross-react with the VCA IgG EIA kit.

Table 3 VCA Cross-Reactive Sera

Serum	VCA IgG	Alternate Assay
1	0.19	1.71	(VZV IgG)
2	0.12	6.03	(VZV IgG)
3	0.13	4.27	(VZV IgG)
4	0.18	3.93	(VZV IgG)
5	0.20	2.29	(CMV IgG)
6	0.16	3.69	(CMV IgG)
7	0.30	3.53	(HSV 1 IgG)
8	0.61	3.26	(HSV 2 IgG)

Sera ≥ 1.10 were considered positive. Sera ≤ 0.90 were considered negative.

. ·

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Image /page/4/Picture/2 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized caduceus symbol, which is a staff with two snakes coiled around it, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" arranged in a circular fashion around the symbol. The text is in all caps and appears to be in a sans-serif font. The logo is black and white.

JUL 221998

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

CLARK LABORATORIES, INC. c/o William L. Boteler, Jr. IMMUNO PROBE, INC. 1306 Bailes Lane, Suite F Frederick, MD 21701

K980912 Re: Trade Name: VCA IgG ELISA Requlatory Class: II Product Code: LSE Dated: April 22, 1998 Received: April 30, 1998

Dear Mr. Boteler:

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 requirement, 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 Reqister. 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 requlation (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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Page 1 of 1

510(k) Number: Not Known

ﻬﺎ ﻓﻬ

Device Name: VCA IgG ELISA

Indications For Use: The Viral Capsid Antigen (VCA) IgG kit is an Enzyme-Linked Immunosorbent Assay (ELISA) for the qualitative determination of IgG antibodies in human serum to VCA antigen. The Clark anti-VCA IgG assay may be used in conjunction with other Epstein-Barr serologies (EA-D IgG, VCA IgM, EBNA-1 IgG, EBNA-1 IgM and heterophile) as an aid in the diagnosis of infectious mononucleosis in a adult population.

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

www.aaaaawaaaauuuuuu Concurrence of CDRH, Office of Device Evaluation (ODE) Prescription Use V OR Over-The Counter Use (Per 21 CFR 801.109) (Optional Format 1-2-96) (Division Sign-C Division of Clinkcal 510(k) Number

Regulation Number and Section

§ 866.3235 Epstein-Barr virus serological reagents.

(a)
Identification. Epstein-Barr virus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to Epstein-Barr virus in serum. The identification aids in the diagnosis of Epstein-Barr virus infections and provides epidemiological information on diseases caused by these viruses. Epstein-Barr viruses are thought to cause infectious mononucleosis and have been associated with Burkitt's lymphoma (a tumor of the jaw in African children and young adults) and postnasal carcinoma (cancer).(b)
Classification. Class I (general controls).