K Number

Device Name

EBV-VCA IGG ELISA TEST, MODEL EBG-100

Manufacturer

PAN BIO PTY. LTD.

Date Cleared

2002-06-13

(101 days)

Product Code

GNP

Regulation Number

866.3235

Intended Use

The Epstein Barr Virus Viral Capsid Antigen (EBV-VCA) IgG ELISA Test is for the qualitative detection of IgG antibodies to EBV-VCA in serum as an aid in the clinical laboratory diagnosis of EBV infection in patients with clinical symptoms consistent with infectious mononucleosis (IM). The PANBIO EBV-VCA IgG ELISA should be used in conjunction with other EBV serologies.

Device Description

The EBV-VCA IgG ELISA Kit is an enzyme-linked immunosorbent assay (ELISA) for the detection of IgG antibodies to EBV-VCA antigen in human serum.

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Center

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Date Received

Product Code

Subsequent Product Codes

Applicant Name (Manufacturer)

Device Name

Decision

Street 1

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ZIP

Postal Code

Class Advise Committee

SSP Indicator

Third Party Reviewed

Expedited Review

Predicate Devices

DiaSorin Incstar EBV-VCA IgG ELISA

Reference Devices

EBV ELISA assays from an alternate manufacturer

AI/ML (Artificial Intelligence / Machine Learning)

No
The summary describes a standard ELISA assay for detecting antibodies, which is a biochemical test and does not involve AI/ML for its operation or interpretation. The performance studies are standard clinical validation methods for diagnostic assays.

Therapeutic

No.
This device is an in-vitro diagnostic (IVD) test used for qualitative detection of antibodies to aid in the diagnosis of EBV infection, not for treating any condition.

Diagnostic

Yes
The device is described as an "aid in the clinical laboratory diagnosis of EBV infection," which directly indicates its use for diagnostic purposes.

SaMD (Software as a Medical Device)

The device description explicitly states it is an "enzyme-linked immunosorbent assay (ELISA) kit," which is a laboratory test 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 explicitly states it's for the "qualitative detection of IgG antibodies to EBV-VCA in serum as an aid in the clinical laboratory diagnosis of EBV infection". This clearly indicates it's used to test a sample taken from the human body (serum) in vitro (outside the body) to provide information for diagnosis.
Device Description: The description confirms it's an "enzyme-linked immunosorbent assay (ELISA) for the detection of IgG antibodies to EBV-VCA antigen in human serum". This further reinforces its function as a test performed on a biological sample.
Intended User / Care Setting: The intended user is a "Clinical laboratory", which is the typical setting for performing in vitro diagnostic tests.

All these elements align with the definition of an In Vitro Diagnostic device.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

Product codes

GNP

Device Description

The EBV-VCA IgG ELISA Kit is an enzyme-linked immunosorbent assay (ELISA) for the detection of IgG antibodies to EBV-VCA antigen in human serum.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

Not Found

Intended User / Care Setting

clinical laboratory for diagnostic aid

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

Not Found

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

Study Site 2: 156 frozen retrospective sera of various ages and genders were submitted to a state health lab in Maryland USA for EBV testing. The sera include samples from the following groups: 28 seronegative samples, 26 samples from patients with acute Infectious Mononucleosis, and 102 samples from patients with past exposure to EBV. These sera were tested on the PANBIO EBV-VCA IgG kit and EBV ELISA assays from an alternate manufacturer to determine the EBV status of the sera. The PANBIO EBV VCA IgG results were compared to the EBV status of the sera to determine the sensitivity, specificity, and agreement of the assay relative to the EBV serological status.

Study Site 3: 352 prospective sera of various ages and genders were tested at a private pathology laboratory in Queensland Australia for EBV testing. The sera include samples from the following groups: 48 seronegative samples, 42 samples from patients with acute Infectious Mononucleosis, and 262 samples from patients with past exposure to EBV. These sera were tested on the PANBIO EBV-VCA IgG kit and EBV ELISA assays from an alternate manufacturer to determine the EBV status of the sera. The PANBIO EBV-VCA IgG results were compared to the EBV status of the sera to determine the sensitivity, specificity, and agreement of the assay relative to the EBV serological status.

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Performance Studies
Study Site 2:

Study Type: Serological Sensitivity and Specificity
Sample Size: 156 frozen retrospective sera
Key Results:
- Serological Sensitivity (Acute) = 18/26 = 69.2 % (95% CI: 48.2 – 85.7 %)
- Serological Sensitivity (Past) = 96/102 = 94.1% (95% CI: 87.6 – 97.8%)
- Serological Specificity (Negative) = 27/28 = 96.4 % (95% CI: 81.6 – 99.9 %)
- Serological Agreement = 141/156 = 90.4 % (95% CI: 84.6 – 94.5 %)

Study Site 3:

Study Type: Serological Sensitivity and Specificity
Sample Size: 352 prospective sera
Key Results:
- Serological Sensitivity (Acute) = 39/42 = 92.9% (95% CI: 80.5 - 98-5%)
- Serological Sensitivity (Past) = 234/262 = 89.3% (95% CI: 85.6-93.1%)
- Serological Specificity (Negative) = 44/48 = 91.7% (95% CI: 80.0 - 97.7%)
- Serological Agreement = 317/352 = 90.1% (95% CI: 86.4-93.0%)

Reproducibility Study

Study Type: Reproducibility
Sample Size: 8 sera tested 3 times each on three different days at three Australian study sites (27 measurements for each sample overall).
Key Results: Within-run, between day, between site and total precision were estimated by analysis of variance (ANOVA Type II).
- Positive Sample Total SD: 0.28, CV: 10.4%
- Cut-off Sample Total SD: 0.05, CV: 4.7%
- Negative Sample Total SD: 0.02, CV: 8.7%

Potential Cross-Reactivity Study

Study Type: Analytical Specificity / Cross-reactivity
Sample Size: 29 specimens from patients with confirmed diseases other than Epstein Barr Virus.
Key Results: No cross-reactivity was observed for any of the 29 specimens tested from the disease panel. Results indicate that no specimens (0/29) were positive.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Study Site 2:

Serological Sensitivity (Acute) = 69.2 %
Serological Sensitivity (Past) = 94.1%
Serological Specificity (Negative) = 96.4 %
Serological Agreement = 90.4 %

Study Site 3:

Serological Sensitivity (Acute) = 92.9%
Serological Sensitivity (Past) = 89.3%
Serological Specificity (Negative) = 91.7%
Serological Agreement = 90.1%

Predicate Device(s)

DiaSorin Incstar EBV-VCA IgG ELISA

Reference Device(s)

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information

Not Found

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).

Summary

JUN 1 3 2002

510(k) SUMMARY OF SAFETY AND EFFECTIVENESS

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

The assigned 510(k) number is: K020706

Applicant Information:

Date Prepared:	07th June, 2002
Name:	PANBIO Limited
Address:	116 Lutwyche Road
Windsor 4030 Australia

Contact Person:	Helen Jennings
Phone Number.	61-(0)7-3357-1177
Fax Number.	61-(0)7-3357-1222

Device Information:

Trade Name:	EBV-VCA IgG ELISA Kit
Common Name.	EBV-VCA IgG EIA Test
Classification Name;	EBV-VCA IgG Serological Reagent

Equivalent Device:

DiaSorin Incstar EBV-VCA IgG ELISA

Device Description:

The EBV-VCA IgG ELISA Kit is an enzyme-linked immunosorbent assay (ELISA) for the detection of IgG antibodies to EBV-VCA antigen in human serum.

Intended Use:

Principle of Procedure:

Serum containing antibodies to VCA antigen, when present, combine with EBV-VCA gp125 antigen attached to the polystyrene surface of the microwells. This antigen is grown in P3HR1 cell lines, and immunopurified utilising a monoclonal specific for gp125. Residual serum is removed by washing and peroxidase conjugated IgG is added. The microwells are washed and a colourless substrate system, anti-human tetramethylbenzidine/hydrogen peroxide (TMB/H2O2) is added. The substrate is hydrolysed by the enzyme and the chromogen changes to a blue colour. After stopping the reaction with acid, the TMB becomes yellow. Color development is indicative of the presence of EBV-VCA IgG antibodies in the test sample.

PERFORMANCE CHARACTERISTICS

Study Site 2:

156 frozen retrospective sera of various ages and genders were submitted to a state health lab in Maryland USA for EBV testing. The sera include samples from the following groups: 28 seronegative samples, 26 samples from patients with acute Infectious Mononucleosis, and 102 samples from patients with past exposure to EBV. These sera were tested on the PANBIO EBV-VCA IgG kit and EBV ELISA assays from an alternate manufacturer to determine the EBV status of the sera. The PANBIO EBV VCA IgG results were compared to the EBV status of the sera to determine the sensitivity, specificity, and agreement of the assay relative to the EBV serological status. The data is summarized in the Table 1.

PANBIO ELISA
EBV Status	Positive	Equivocal*	Negative	Total
Seronegative
VCA IgG (-)
VCA IgM (-)
EBNA IgG (-)	1	0	27	28
Acute
VCA IgM (+)
EBNA IgG (-)	18	4	4	26
Past Infection
VCA IgG (+)
VCA IgM (-)
EBNA IgG (+)	96	2	4	102
Total	115	6	35	156

TABLE 1 EBV VCA IgG Serological Sensitivity and Specificity of PANBIO ELISA versus EBV Status

95% Confidence Interval

Serological Sensitivity (Acute)	= 18/26	= 69.2 %	48.2 – 85.7 %
Serological Sensitivity (Past)	= 96/102	= 94.1%	87.6 – 97.8%
Serological Specificity (Negative)	= 27/28	= 96.4 %	81.6 – 99.9 %
Serological Agreement	= 141/156	= 90.4 %	84.6 – 94.5 %

Retesting of equivocal samples was not conducted, as the samples were unavailable.

Note: "Serological" sensitivity and specificity refers to the Comparison of the PANBIO assay results to that of other assays normally used to diagnose EBV associated IM. There was not an attempt to correlate the assay's results with disease presence or absence. No judgement can be made on the comparison's accuracy to predict disease. Since the above studies were performed on a pre-selected, retrospective, populations for the assay's positive and negative predictive value may be done or inferred.

Study Site 3:

352 prospective sera of various ages and genders were tested at a private pathology laboratory in Queensland Australia for EBV testing. The sera include samples from the following groups: 48 seronegative samples, 42 samples from patients with acute Infectious Mononucleosis, and 262 samples from patients with past exposure to EBV. These sera were tested on the PANBIO EBV-VCA IgG kit and EBV ELISA assays from an alternate manufacturer to determine the EBV status of the sera. The PANBIO EBV-VCA IgG results were compared to the EBV status of the sera to determine the sensitivity, specificity, and agreement of the assay relative to the EBV serological status. The data is summarized in Table 2.

	PANBIO ELISA
EBV Status	Positive	Equivocal*	Negative	Total
Seronegative
VCA IgG (-)
VCA IgM (-)
EBNA IgG (-)	4	0	44	48
Acute
VCA IgM (+)
EBNA IgG (-)	39	0	3	42
Past Infection
VCA IgG (+)
VCA IgM (-)
EBNA IgG (+)	234	1	27	262
Total	277	1	74	352
Serological Sensitivity (Acute)		= 39/42	= 92.9%	95% Confidence Interval
80.5 - 98-5%
Serological Sensitivity (Past)		= 234/262	= 89.3%	85.6-93.1%
Serological Specificity (Negative)	= 44/48		= 91.7%	80.0 - 97.7%
Serological Agreement		= 317/352	= 90.1%	86.4-93.0%

TABLE 2
EBV VCA IgG Serological Sensitivity and Specificity of
PANBIO ELISA versus EBV Status

*This equivocal sample was not tested on an alternative method due to insufficient sample. Collection of a further sample was not possible.

REPRODUCIBILITY

The reproducibility of the PANBIO EBV-VCA IgG ELISA kit was determined by testing 8 sera 3 times each on three different days at three Australian study sites. Two sites were private pathology laboratories and the third site was PANBIO. Within-run, between day, between site and total precision were estimated by analysis of variance (ANOVA Type II) and are presented in table 3 below.

Sample	n	*Mean	Within		Between Day		Between Site		Total
			*S.D	CV	*S.D	CV	*S.D	CV	*S.D	CV
Positive	27	2.71	0.24	9.0%	0.12	4.5%	0.12	4.5%	0.28	10.4%
Cut-off	27	1.00	0.06	5.7%	0.00	0.0%	0.00	0.0%	0.05	4.7%
Negative	27	0.19	0.02	8.5%	0.00	2.6%	0.00	0.0%	0.02	8.7%
#1	27	2.08	0.21	10.2%	0.07	3.6%	0.11	5.4%	0.24	11.5%
#2	27	3.29	0.24	7.3%	0.00	0.0%	0.16	5.0%	0.27	8.3%
#3	27	1.47	0.12	8.5%	0.07	5.0%	0.07	4.6%	0.15	10.2%
#4	27	1.24	0.08	6.8%	0.01	1.0%	0.05	4.0%	0.09	7.6%
#5	27	0.89	0.08	9.5%	0.05	6.1%	0.04	4.4%	0.10	11.3%
#6	27	1.13	0.08	7.0%	0.00	0.0%	0.04	3.7%	0.08	7.5%
#7	27	2.24	0.27	11.9%	0.07	3.0%	0.19	8.6%	0.32	14.1%
#8	27	3.74	0.27	7.2%	0.01	0.4%	0.18	4.9%	0.31	8.3%

TABLE 3 - REPRODUCIBILITY DATA PANBIO EBV-VCA IgG Study Site 1, 2 & 3 Precision Measures (Using Cut-Off Ratio)

All values are calculated from Ratios (Cut-Off using O.D) SD = Standard Deviation; CV = Coefficient of Variation

Note: Standard Deviation results have been rounded to two decimal places for tabulation purposes

POTENTIAL CROSS-REACTIVITY

Study Site 5:

A panel of 29 specimens from patients with confirmed diseases other than Epstein Barr Virus was tested to establish the analytical specificity of the EBV-VCA IgG ELISA Test. The specimens were from patients with diseases that have the potential for cross-reactivity. Each of the specimens included in the study was characterized with respect to disease diagnosis prior to analysis with the EBV-VCA IgG ELISA Test. No crossreactivity was observed for any of the 29 specimens tested from the disease panel. Refer to Table 4 for a summary of the results.

TABLE 4

Disease Type	Total Specimens	Positive Result
Cytomegalovirus	7	(0/7)
Varicella zoster	9	(0/9)
Herpes Simplex virus 1	6	(0/6)
Herpes Simplex virus 2	1	(0/1)
Anti-Nuclear Antigen	3	(0/3)
Rheumatoid Factor	3	(0/3)
Total	29	(0/29)

PANBIO EBV-VCA IgG CROSS-REACTIVITY SPECIMEN PANEL

Results indicate that no specimens (0/29) were positive when analysed with the EBV-VCA IgG ELISA Kit. Refer to 'Study Document -- Site 5' for raw data and section 2.3.4.1 for the summary table.

The true negative result of 100% for the above disease panel is consistent with good analytical specificity for the EBV-VCA IgG ELISA Test.

Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of the department's name arranged in a circular fashion around a symbol. The symbol is a stylized representation of three human profiles facing to the right, stacked on top of each other.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JUN 1 3 2002

Ms. Helen Jennings Quality and Regulatory Affairs Manager PANBIO Limited 116 Lutwyche Road Windsor. Brisbane Queensland, 4030 Australia

Re: K020706

Trade/Device Name: Epstein Barr Virus VCA IgG ELISA Test Regulation Number: 21 CFR 866.3235 Regulation Name: Epstein - Barr virus Serological Reagents Regulatory Class: Class I Product Code: GNP Dated: May 9, 2002 Received: May 15, 2002

Dear Ms. Jennings:

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 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) 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, 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 (PMA), 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 898. 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 Part 801); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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 v 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" (21CFR 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 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): K020706

Device Name:

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 Deibres

Unical Laboratory Devices

PRESCRIPTION USE X

(Optional Format 3-10-98)