K Number

Device Name

EA-D IGM ELISA TEST SYSTEM

Manufacturer

COLUMBIA BIOSCIENCE, INC.

Date Cleared

1998-11-25

(142 days)

Product Code

LSE

Regulation Number

866.3235

Intended Use

For the qualitative determination of IgM antibodies in human serum to Epstein Barr (recombinant) early antigen diffuse (EA-D) antigen. The & EA-D IgM assay should be used in conjunction with other Epstein-Barr serologies (VCA IgM, VCA IgG, EBNA-1 IgG, EBNA-1 IgM, EA-D IgG and heterophile) as an aid in the diagnosis of infectious mononucleosis. The test can be performed either manually or in conjunction with the MAGO PLUS The Automated EIA Processor.

Device Description

The & EA-D IgM ELISA Kit is an enzyme-linked immunosorbent assay (ELISA) for the detection of IgM antibodies to Epstein-Barr Early antigen diffuse in human serum.

More Information

Contact

Type

Center

Panel

Date Received

Product Code

Subsequent Product Codes

Applicant Name (Manufacturer)

Device Name

Decision

Street 1

Street 2

City

State

Country Code

ZIP

Postal Code

Class Advise Committee

SSP Indicator

Third Party Reviewed

Expedited Review

Predicate Devices

Not Found

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The summary describes a standard ELISA kit and an automated processor, neither of which are described as using AI/ML. The performance studies and metrics are typical for serological assays.

Therapeutic

No
This device is an in vitro diagnostic (IVD) test for detecting antibodies, not a therapeutic device. It is used as an aid in diagnosis, not for treatment.

Diagnostic

Yes

The device is explicitly stated to be used "as an aid in the diagnosis of infectious mononucleosis," which falls under the definition of a diagnostic device.

SaMD (Software as a Medical Device)

The device description explicitly states it is an "ELISA Kit," which is a laboratory assay involving physical reagents and procedures, not solely software. It also mentions being used "manually or in conjunction with the MAGO PLUS The Automated EIA Processor," indicating hardware components are involved in its use.

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 determination of IgM antibodies in human serum" and is used "as an aid in the diagnosis of infectious mononucleosis." This clearly indicates it's used to test samples taken from the human body (in vitro) to provide information for diagnostic purposes.
Device Description: The description confirms it's an "enzyme-linked immunosorbent assay (ELISA) for the detection of IgM antibodies... in human serum." This further reinforces that it's a test performed on a biological sample outside of the body.
Performance Studies: The performance studies describe testing "human serum" samples and evaluating the device's performance in terms of sensitivity and specificity for diagnosing infectious mononucleosis.

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

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

For the qualitative determination of IgM antibodies in human serum to Epsien Barr Virus (recombinant) Early antigen (EA-D) antigen. The & EA-D IgG assay should be used in conjunction with other Epstein-Barr serologies (VCA IgM. VCA IgG. EBNA-1 IgM and heterophile) as an aid in the diagnosis of infectious mononucleosis. The test can be performed either manually or in conjunction with the MAGO PLUS TM Automated EIA Processor.

Product codes (comma separated list FDA assigned to the subject device)

Not Found

Device Description

The & EA-D IgM ELISA Kit is an enzyme-linked immunosorbent assay (ELISA) for the detection of IgM antibodies to Epstein-Barr Early antigen diffuse 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

Not Found

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

Not Found

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

A. Clinical Sensitivity and Specificity Using Characterized Sera
Frozen retrospective sera from one hundred and seventy-six patients were characterized using commercially available kits for VCA IgM, VCA IgG, EBNA IgG and heterophile antibodies. The patient sera were characterized as: 102 convalescent (past infection), 32 seronegative, and 42 current (recent) infection.
All 176 sera were then tested by an independent clinical commercial laboratory using the Is-EBV-EA-D IgM Test Kit.
Results obtained: For Convalescent, 5 were POSITIVE, 93 NEGATIVE, 4 EQUIVOCAL. For Current Infection, 17 POSITIVE, 20 NEGATIVE, 5 EQUIVOCAL. For Seronegative, 1 POSITIVE, 29 NEGATIVE, 2 EQUIVOCAL. (Equivocal results were excluded from calculations).
Key Metrics: Relative Specificity (Convalescent) = 93/98 = 94.9% (95% CI 88.5-98.3%), Relative Sensitivity (Current Infection) = 17/37 = 45.9% (95% CI 29.5-63.1%), Relative Specificity (Seronegative) = 29/30 = 96.7% (95% CI 82.8-99.9%). Overall Agreement = 139/165 = 84.2% (95% CI 78.7-89.8%).
Note: "relative" refers to comparison to a similar assay; no correlation to disease presence/absence or positive predictive value can be inferred from this pre-selected, retrospective population.

B. Precision
Four positive and two negative sera were assayed ten times each in three different runs at three different sites (manufacturer, research and development laboratory, clinical commercial laboratory).
Site #1 (Manufacturer): Intra-assay and Interassay Precision results presented for 6 sera (A-POS, B-POS, C-POS, D-POS, E-NEG, F-NEG) and control samples (CAL, PC, NC) including Mean Index and CV%.
Site #2: Intra-assay and Interassay Precision results presented for 6 sera (A-POS, B-POS, C-POS, D-POS, E-NEG, F-NEG) and control samples (CAL, PC, NC) including Mean Index and CV%.
Site #3: Intra-assay and Interassay Precision results presented for 6 sera (A-POS, B-POS, C-POS, D-POS, E-NEG, F-NEG) and control samples (CAL, PC, NC) including Mean Index and CV%.
Inter-Site Precision (n=90 for sera, n=36 for CAL, n=18 for LPC & NC): Mean Index and CV% for 6 sera and CAL, LPC, NC.

C. Specificity with Potentially Cross-Reactive Sera
Thirteen sera, non-reactive (negative) for IgM antibodies to EA-D in the Is-EBV-EA-D IgM Test Kit, were tested by EIA for IgM antibody to varicella zoster, cytomegalovirus and herpes simplex virus. 4/4 anti-VZV IgM positive sera were non-reactive for anti-EA-D IgM; 3/5 anti-CMV IgG positive sera were non-reactive for anti-EA-D IgM and 4/4 anti-HSV positive sera were non-reactive for anti-EA-G IgM. This suggests that some cross-reactivity should be expected with the Is-FA-D IgM Test Kit from these analytes.

D. Correlation of Manual and MAGO Plus Results
128 serum samples were tested by both manual and MAGO Plus Automated EIA Processor methods. A scattergram and regression line showed good correlation with a Pearson Correlation Coefficient of 0.975. The regression line equation is Y = 0.0657 + 0.9423 X.

E. MAGO Plus Precision
The precision using the MAGO Plus Automated EIA Processor was determined by assaying six sera ten times each in three different runs.
Results presented for 6 sera (A-POS, B-POS, C-POS, D-POS, E-NEG, F-NEG) and control samples (CAL, PC, NC) including Mean Index and CV% for intra-assay and interassay precision.

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

Relative Specificity (Convalescent) = 93/98 = 94.9%
Relative Sensitivity (Current Infection) = 17/37 = 45.9%
Relative Specificity (Seronegative) = 29/30 = 96.7%
Overall Agreement = 139/165 = 84.2%

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

Not Found

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

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

NOV 2 5 1998

K982352

510k 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:

Applicant Information:

Date Prepared:	March 23, 1998
Name:	Columbia Bioscience, Inc.
Address:	8775 M Centre Park Drive, #559
Columbia, MD 21045

Contact Person:	Norman Jenkins
PhoneNumber.	410-995-0450
Fax Number.	410-995-0448

Device Information:

Trade Name:	EA-D IgM ELISA Kit
Common Name.	EA-D IgM EIA Test
Classification Name;	Epstein-Barr Virus

Equivalent Device: EBV Serology

Device Description: The & EA-D IgM ELISA Kit is an enzyme-linked immunosorbent assay (ELISA) for the detection of IgM antibodies to Epstein-Barr Early antigen diffuse in human serum.

Intended Use: For the qualitative determination of IgM antibodies in human serum to Epsien Barr Virus (recombinant) Early antigen (EA-D) antigen. The & EA-D IgG assay should be used in conjunction with other Epstein-Barr serologies (VCA IgM. VCA IgG. EBNA-1 IgM and heterophile) as an aid in the diagnosis of infectious mononucleosis. The test can be performed either manually or in conjunction with the MAGO PLUS TM Automated EIA Processor.

Principle of Procedure:

The & EA-D IgG ELISA Kit is an enzyme-linked immunosorbent assay to detect IgG to EA-D in human serum. Recombinant EA-D antigen is attached to a solid phase (microtiter well). Diluted test sera are added to each well. If antibodies which recognize the. EA-D antigen are present in the patient sample they will bind to the antigen in the well. After incubation, the wells are washed to remove unbound antibody. An enzyme labeled anti-human immunoglobulin (conjugate) is added to each test well. If antibody is present the enzyme-linked antibody will bind to it. After incubation, the wells are washed to remove unbound conjugate. A substrate solution is then added to each well. If enzyme is present from prior step, the reaction is stopped and the, color intensity is measured photometrically producing an indirect detection of the specific antibody present in the patient sample.

Performance Characteristics

A. Clinical Sensitivity and Specificity Using Characterized Sera

Frozen retrospective sera from one hundred and seventy-six patients were characterized using commercially available kits for VCA IgM, VCA IgG, EBNA IgG and heterophile antibodies. Based on the results of this testing, the patient sera were characterized as follows:

102 sera were characterized as convalescent (past infection). These were positive for VCA IgG and/or EBNA IgG antibodies and negative for VCA IgM and heterophile antibody.
32 sera were characterized as scronegative. These were negative for VCA IgG, VCA IgM, EBNA IgG and heterophile antibody.
42 sera were characterized as having a current (recent) infection. These were positive for VCA IgM and/or heterophile antibody and were negative for EBNA IgG.

All 176 sera were then tested by an independent clinical commercial laboratory using the Is-EBV-EA-D IgM Test Kit. The results obtained are shown in Table 2:

	TABLE 2	EBV Serological Status
		Convalescent	Current Infection	Seronegative
	POSITIVE	5	17	. 1
Is-EBV-EA-D-IgM	NEGATIVE	93	20	29
	*EQUIVOCAL	4	5	2

			95% CI
Relative Specificity (Convalescent)	93/98	= 94.9%	88.5-98.3%
Relative Sensitivity (Current Infection)	17/37	= 45.9%	29.5-63.1%
Relative Specificity (Seronegative)	29/30	= 96.7%	82.8-99.9%
Overall Agreement	139/165	= 84.2%	78.7-89.8%

ERV Serological Status

Equivocal results were excluded from calculations

NOTE : Please be advised that 'relative' refers to the comparison of the assay's results to that of a similar assay. There was not an attempt to correlate the assay's results with disease presence or absence. No judgment can be made on the comparison's accuracy to predict disease. Since the above studies were performed on a pre-selected, retrospective population, no calculations for the assay's positive predictive value may be done or inferred.

B.Precision

Todclerminethe precisionofthels-EBV-EA-DIgMTestKit, fourpositive and wonegativesera were assayed ten timescachinthreedifferentrunsatthreedifferentsites. The3sitesinclude: themanufacturer, arescarchanddevelopmentlaboratory,andaclinicalcommerciallaboratory. Theintra-andinterassayprecisionobtainedateachsiteis showninTables3,4and5.TheInter-SiteprecisionisshowninTable6.

SERUM	INTRA-ASSAY RUN 1		INTRA-ASSAY RUN 2		INTRA-ASSAY RUN 3		INTERASSAY
	MEAN INDEX	CV%	MEAN INDEX	CV%	MEAN INDEX	CV%	MEAN INDEX	CV%
A (POS)	6.59	5.42	6.37	4.53	6.25	5.17	6.40	5.35
B (POS)	1.86	12.60	1.79	10.84	1.95	6.18	1.87	10.46
C (POS)	2.90	10.05	2.67	7.31	2.61	9.00	2.73	9.77
D (POS)	1.37	8.92	1.38	12.45	1.41	12.81	1.39	11.20
E (NEG)	0.14	44.84	0.15	39.58	0.16	46.08	0.15	42.74
F (NEG)	0.44	15.23	0.45	39.42	0.32	35.23	0.40	34.16
						CAL	0.97	10.49	n = 9
						PC	1.65	12.75	n = 3
						NC	0.29	38.40	n = 3

TABLE 4 : Site #2- Intra-Assay and Interassay Precision

SERUM		INTRA-ASSAY RUN 1	INTRA-ASSAY RUN 2	INTRA-ASSAY RUN 3	INTERASSAY
	MEAN
INDEX	MEAN
INDEX	CV%	MEAN
INDEX	CV%	MEAN
INDEX	CV%	MEAN
INDEX	CV%
A (POS)	6.328	6.78	5.514	4.34	6.055	3.85	5.966	7.68
B (POS)	1.813	9.32	1.580	10.07	1.722	6.65	1.705	10.21
C (POS)	2.465	5.70	2.376	17.21	2.521	6.15	2.454	10.72
D (POS)	1.261	4.89	1.118	6.07	1.219	3.78	1.199	6.97
E (NEG)	0.144	28.01	0.155	16.49	0.150	14.21	0.149	19.71
F (NEG)	0.289	15.47	0.341	8.87	0.308	10.00	0.313	13.11
					CAL	1.001	4.69	n = 18
					PC	1.564	12.03	n = 12
					NC	0.303	4.72	n = 12

			TABLE 5 : Site #3 - Intra-assay and Interassay Precision
--	--	--	----------------------------------------------------------	--

SERUM	INTRA-ASSAY RUN 1		INTRA-ASSAY RUN 2		INTRA-ASSAY RUN 3		INTERASSAY
	MEAN
INDEX	CV%	MEAN
INDEX	CV%	MEAN
INDEX	CV%	MEAN
INDEX	CV%
A (POS)	6.35	11.01	6.53	12.63	6.05	11.29	6.31	11.74
B (POS)	1.98	9.08	1.90	10.74	1.91	11.87	1.93	10.36
C (POS)	2.63	16.02	2.59	15.59	2.52	17.40	2.58	15.86
D (POS)	1.55	20.22	1.49	26.10	1.42	14.80	1.49	20.67
E (NEG)	0.13	15.27	0.12	19.99	0.13	23.17	0.13	19.85
F (NEG)	0.29	15.16	0.24	15.18	0.36	10.88	0.29	21.96
						CAL	1.00	11.59
						PC	1.42	6.45
						NC	0.30	5.77

Table 6 : Inter-Site Precision

| SERUM

(n=90)	INTER-SITE
	MEAN
INDEX	CV%
A (POS)	6.23	9.10
B (POS)	1.83	11.51
C (POS)	2.58	12.97
D (POS)	1.36	17.32
E (NEG)	0.14	31.41
F (NEG)	0.34	30.28
CAL (n=36)	0.99	8.21
LPC (n=18)	1.55	11.87
NC (n=18)	0.30	13.42

C. Specificity with Potentially Cross-Reactive Sera

Thirteen sera, non-reactive (negative) for IgM antibodies to EA-D in the Is-EBV-EA-D IgM Test Kit, were tested by EIA for IgM antibody to varicclla zoster, cytomegalovirus and herpes simplex virus. 4/4 anti-VZV IgM positive scra were non-reactive for anti-EA-D IgM; 3/5 anti-CMV IgG positive sera were non-reactive for anti-EA-D IgM and 4/4 anti-HSV positive scra were non-reactive for anti-EA-G IgM. This suggests that some cross-reactivity should be expected with the Is-FA-D IgM Test Kit from these analytes.

D. Correlation of Manual and MAGO Plus Results

The Is-I'D V-EA-D IgM Test Kit has been developed for automated as well as manual use. To demonstrate the equivalence of the manual and MAGO Plus procedures, the results of 128 serum samples tested by both methods were plotted. A scattergram and regression line of the results obtained with 95% confidence intervals is shown in Figure 3. The data indicate good correlation with a Pearson Correlation Coefficient of 0.975.

Image /page/3/Figure/4 description: This image is a scatter plot comparing "MAGO PLUS INDEX VALUES" on the y-axis and "MANUAL INDEX VALUES" on the x-axis. The data points are clustered around a regression line, indicating a positive correlation between the two variables. The equation of the regression line is given as Y = 0.0657 + 0.9423 X, and the correlation coefficient (r) is 0.975, suggesting a strong linear relationship.

FIGURE 3 : Manual and MAGO Plus Result Correlation

E. MAGO Plus Precision

The precision of the assay when performed on the MAGO Plus Automated EIA Processor was determined by assaying six sera ten times each in three different runs. Table 7 shows the intra-and interassay precision obtained using the MAGO Plus.

TABLE 7 : Site #2- Intra-Assay and Interassay Precision - MAGO Plus

| SERUM | INTRA-ASSAY RUN 1
MEAN
INDEX | INTRA-ASSAY RUN 1
CV% | INTRA-ASSAY RUN 2
MEAN
INDEX | INTRA-ASSAY RUN 2
CV% | INTRA-ASSAY RUN 3
MEAN
INDEX | INTRA-ASSAY RUN 3
CV% | INTERASSAY
MEAN
INDEX | INTERASSAY
CV% |
|---------|------------------------------------|--------------------------|------------------------------------|--------------------------|------------------------------------|--------------------------|-----------------------------|-------------------|
| A (POS) | 6.1 | 3.76 | 5.8 | 4.29 | 5.8 | 3.98 | 5.9 | 4.35 |
| B (POS) | 1.8 | 6.38 | 1.7 | 7.27 | 1.8 | 8.12 | 1.8 | 7.44 |
| C (POS) | 2.7 | 5.51 | 2.5 | 7.23 | 2.6 | 7.49 | 2.6 | 6.97 |
| D (POS) | 1.4 | 16.10 | 1.3 | 7.77 | 1.3 | 8.34 | 1.3 | 11.76 |
| E (NEG) | 0.1 | 37.16 | 0.1 | 28.75 | 0.1 | 0.00 | 0.1 | 30.51 |
| F (NEG) | 0.3 | 23.80 | 0.3 | 20.45 | 0.3 | 15.06 | 0.3 | 20.86 |
| | | | | | | CAL | 1.0 | 2.80 |
| | | | | | | PC | 1.7 | 3.50 |
| | | | | | | NC | 0.4 | 0.00 |

Image /page/4/Picture/1 description: The image shows the seal of the Department of Health & Human Services (HHS) of the United States of America. The seal features the department's name encircling a symbol. The symbol consists of a stylized caduceus, which is a traditional symbol of medicine, with three figures representing health and human services. The text is arranged in a circular pattern around the symbol.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

NOV 25 1998

Norman Jenkins President Columbia Bioscience, Inc. 8775 M Centre Park Drive, #559 Columbia, Maryland 21045

Re: K982350 Device: EA-D IgM ELISA Test System Dated: September 22, 1998 Received: September 28, 1998

Dear Mr. Jenkins:

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 OS 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.

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 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 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

Page 1 of 1

510(k) Number: Not Known

Device Name: & EA-D IgM ELISA

Indications For Use: For the qualitative determination of IgM antibodies in human serum to Epstein Barr (recombinant) early antigen diffuse (EA-D) antigen. The & EA-D IgM assay should be used in conjunction with other Epstein-Barr serologies (VCA IgM, VCA IgG, EBNA-1 IgG, EBNA-1 IgM, EA-D IgG and heterophile) as an aid in the diagnosis of infectious mononucleosis. The test can be performed either manually or in conjunction with the MAGO PLUS The Automated EIA Processor.

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)

Over-The Counter Use (Optional Format 1-2-96)

Woody Dubois

inical I aboratory Devices 510(k) Number