The Diamedix Is-HSV 1 & 2 IgG is an indirect Enzyme Immunoassay (EIA) for the qualitative and semi-quantitative determination of IgG antibodies to herpes simplex virus (HSV) type 1 and/ or type 2 in human serum. This test is useful for indicating a past infection with HSV in a single specimen, including females of child-bearing age. The evaluation of acute and convalescent specimens, by demonstrating seroconversion or a significant increase in antibody level, can aid in the diagnosis of primary infection with HSV. These reagents can be used either manually or in conjunction with the MAGO® Plus Automated EIA Processor.

Device Description

The Is-HSV 1 & 2 IgG Test System is an enzyme-linked immunosorbent assay (ELISA) for the detection and semi-quantitation of IgG to HSV 1 and/or HSV 2 antigens in human serum

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly stated in a quantitative manner (e.g., "sensitivity must be > X%"). Instead, the study aims to demonstrate "substantial equivalence" to a legally marketed predicate device (Incstar HSV I/II IgG "fast" ELISA Kit). The performance data presented shows the agreement, sensitivity, and specificity of the new device relative to this predicate device across multiple sites. The implicit acceptance criterion is that the new device performs comparably to the predicate.

Acceptance Criteria (Implied: Substantial Equivalence to Predicate Device)	Reported Device Performance (Relative to Predicate/Other Legally Marketed Devices)
Relative Sensitivity (High agreement with positive cases of predicate)	Site 1: 100.0% (97.7-100.0%)
	Site 2: 99.2% (95.4-100.0%)
	Site 3 (manual): 100.0% (98.3-100.0%)
	Site 3 (automated): 99.5% (97.4-100.0%)
Relative Specificity (High agreement with negative cases of predicate)	Site 1: 92.7% (80.1-98.5%)
	Site 2: 94.7% (85.4-98.9%)
	Site 3 (manual): 100.0% (93.4-100.0%)
	Site 3 (automated): 97.8% (88.5-99.9%)
Overall Agreement	Site 1: 98.5% (95.6-99.7%)
	Site 2: 97.7% (94.3-99.4%)
	Site 3 (manual): 100.0% (98.6-100.0%)
	Site 3 (automated): 99.2% (97.2-99.9%)
Precision (Intra-assay CV)	1.4 to 18.7% for positive samples
Precision (Inter-assay CV)	3.5 to 15.5% for positive samples
Linearity (for semi-quantitative aspect)	Demonstrated linear relationship between EU/ml values and log of serum dilution for strongly positive samples.
No detectable cross-reactivity	No detectable cross-reactivity to VZV, CMV, EBV, measles, rubella, or Toxoplasma.

2. Sample Size Used for the Test Set and Data Provenance

Sample Size for Test Set: A total of 645 different patient sera were evaluated across 3 test sites.
Data Provenance: Not explicitly stated regarding country of origin. The study was a "Performance Data" evaluation, implying it was a prospective or retrospective collection of patient sera for the purpose of testing the device. It was tested at "3 different test sites," suggesting real-world clinical samples, but whether they were newly collected (prospective) or previously banked (retrospective) is not specified. The CDC serum panel for HSV serology assays was also tested, which suggests a well-characterized, potentially external, reference set.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

Number of Experts: Not specified.
Qualifications of Experts: Not specified.

4. Adjudication Method for the Test Set

The text states the Is-HSV 1 & 2 IgG Test System was "evaluated relative to the predicate device and to other legally marketed devices". This implies the predicate device and other legally marketed devices served as the reference standard (ground truth). It is not specified if there was a separate expert adjudication process to establish the ground truth for the 645 patient sera. Equivocal samples were excluded from calculations, but the method for resolving discrepancies or establishing initial truth is not detailed beyond comparison to existing devices.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, a MRMC comparative effectiveness study was not done. This study is focused on an in-vitro diagnostic (IVD) ELISA test, not an imaging device requiring human interpretation, so the concept of "human readers" and "AI assistance" in the traditional sense of an MRMC study does not apply.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, this was a standalone performance study. The device itself is an ELISA test system designed to detect antibodies. Its performance (sensitivity, specificity, agreement) was evaluated directly, both manually and with an automated processor (MAGO Plus), without a human-in-the-loop scenario where a physician interprets the results with or without the device's output. The device is the "algorithm" in this context, providing a direct measurement.

7. The Type of Ground Truth Used

Comparison to legally marketed devices (predicate and others). The performance of the Is-HSV 1 & 2 IgG Test System was evaluated "relative to the predicate device and to other legally marketed devices." This means the results from these established, cleared tests served as the reference or "ground truth" against which the new device was compared. Additionally, the CDC serum panel for HSV serology assays was used, which represents a highly characterized reference standard.

8. The Sample Size for the Training Set

Not applicable / Not specified. ELISA assay development does not typically involve a "training set" in the same way machine learning algorithms do. The development involves optimizing reagents, conditions, and cutoff values through laboratory studies, but not a distinct "training set" of patient samples for algorithm learning.

9. How the Ground Truth for the Training Set Was Established

Not applicable. As noted above, the concept of a training set and its ground truth establishment in the machine learning sense does not apply to this type of IVD device development. The performance characteristics of the assay (e.g., linearity, cross-reactivity, precision) would be established through laboratory experiments and optimization during development.

Summary

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K981306

SEP 2 9 1998

510(k) Summary

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

K981306 The assigned 510(k) number is:

Applicant Information:

Date Prepared:	September 28, 1998
Submitter's Name:	Diamedix Corporation
Address:	2140 N. Miami AvenueMiami, FL 33127

Contact Person:	Dr. Lynne Stirling
Phone Number:	305-324-2354
Fax Number:	305-324-2585

Device Information:

Trade Name:	Is-HSV 1 & 2 IgG Test System
Common Name:	HSV EIA Test
Classification Name:	Enzyme linked immunosorbent assay, herpes simplex virus

Equivalent Device Description:

Incstar HSV I/II IgG "fast" ELISA Kit

The Incstar Herpes Simplex Virus VII IgG "fast" ELISA kit contains instructions and materials for the qualitiative and semi-quantitative detection of IgG antibodies to herpes simplex virus type 1 and/or type 2 in human serum by indirect ELISA.

Device Description: The Is-HSV 1 & 2 IgG Test System is an enzyme-linked immunosorbent assay (ELISA) for the detection and semi-quantitation of IgG to HSV 1 and/or HSV 2 antigens in human serum

Device Intended Use: This device is intended for the qualitative and semi-quantitative detection of IgG antibodies to herves simplex virus (HSV) type 1 and/or type 2 in human serum. This test is useful for indicating a past infection with HSV in a single specimen, including females of child-bearing age. The evaluation of acute and convalescent specimens, by demonstrating seroconversion or a significant increase in antibody level, can aid in the diagnosis of primary infection with HSV. These reagents can be used either manually or in conjunction with the MAGO Plus Automated Processor.

Principle of the Procedure:

The Is-HSV 1 & 2 IgG Test System is an enzyme-linked immunosorbent assay to detect IgG to HSV1 and/or HSV 2 in human serum. Purified HSV 1 and 2 antigens are attached to a solid phase microtiter well. Diluted test sera are added to each well. If antibodies which recognize the HSV antigens are present in the patient sample they will bind to the antigens on the well. After incubation, the wells are washed to remove unbound antibody. An enzyme

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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 the prior step, the reaction is stopped and the color intensity is measured photometrically producing an indirect measure of the specific antibody present in the patient sample.

The Is-HSV 1 & 2 IgG Test System and the Incstar HSV I/II IgG "fast" ELISA are substantially equivalent in that :

1. Both are in vitro immunologic methods
1. Both are intended for use in the detection of IgG antibody to herpes simplex virus type 1 and/or type 2 in human serum.
1. Both are based on the formation of a complex between HSV antigens and antibody
1. Both use antigen coated microtiter plates
1. Both are qualitative/semi-quantitative assays
1. Both use goat anti-human IgG conjugated to horseradish peroxidase
1. Both use TMB as the enzyme substrate.

A detailed comparison between the proposed device and the predicate device is shown in Table 1.

Performance Data : The Is-HSV 1 & 2 IgG Test System was evaluated relative to the predicate device and to other legally maketed devices at 3 different test sites. In addition, the CDC serum panel for HSV serology assays was tested with this device.

A total of 645 different patient sera were evaluated. Thes results of these comparisons are shown below :

	# of Sera	RelativeSensitivity (%)	RelativeSpecificity (%)	OverallAgreement* (%)
Site 1	200	100.0(97.7-100.0)	92.7(80.1-98.5)	98.5(95.6-99.7)
Site 2	178	99.2(95.4-100.0)	94.7(85.4-98.9)	97.7(94.3-99.4)
Site 3 (manual)	267	100.0(98.3-100.0)	100.0(93.4-100.0)	100.0(98.6-100.0)
Site 3 (automated)	259	99.5(97.4-100.0)	97.8(88.5-99.9)	99.2(97.2-99.9)

equivocal samples were not included in calculations

) 95% confidence interval (

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The precision of the Is-HSV1 & 2 IgG Test Sytem was determined at 3 testing sites by testing several sera in two different runs per day for threee days. Intra-assay CVs for positive samples ranged from 1.4 to 18.7%. Interassay CVs for positive samples ranged from 3.5 to 15.5%.

Studies were also conducted to show the correlation between manual and autmated methods for samples within the assay's critical range (20-100 EU/ml).

The titration of strongly positive sampes demonstrate a linear relationship between the Is-HSV 1 & 2 IgG EU/ml values and the log of the serum dilution.

Studies undertaken to determine cross-reactivity of the Is-HSV 1 & 2 IgG Test System demonstrated no detectable cross-reactivity to varicella zoster virus, cytomegalovinus, Epstein Barr virus, measles virus, rubella virus or Toxoplasma.

Conclusions : The Diamedix Is-HSV 1 & 2 IgG is substantially equivalent to the Incstar HSV VII "fast" ELISA for the detection of IgG antibodies to herpes simplex virus in human serum to aid in the indication of a past infection or, in the case of paired samples, as an aid in the diagnosis of a primary infection. The device is as safe, as effective and performs as well as the legally marketed device described.

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Public Health Service

Image /page/3/Picture/2 description: The image shows the logo for the Department of Health & Human Services USA. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized image of an eagle or bird-like figure, with three curved lines forming the body and wings.

SEP 2 9 1998

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Lynne Stirling, Ph.D. Vice President, Regulatory Affairs Diamedix Corporation 2140 N. Miami Ave. Miami, FL 33127

Re: K981306 Trade Name: Is-HSV 1 & 2 IgG Test System Regulatory Class: III Product Code: LGC Dated: July 14, 1998 Received: July 17, 1998

Dear Dr. Stirling:

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 Autman

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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Appendix G Rev. Indications for Use Statement

INDICATIONS FOR USE STATEMENT

510(K) Number : _ K 981366

DEVICE NAME : Is-HSV 1 & 2 IgG Test System

Indications for Use : The Diamedix Is-HSV 1 & 2 IgG is an indirect Enzyme Immunoassay (EIA) for the qualitative and semi-quantitative determination of IgG antibodies to herpes simplex virus (HSV) type 1 and/ or type 2 in human serum. This test is useful for indicating a past infection with HSV in a single specimen, including females of child-bearing age. The evaluation of acute and convalescent specimens, by demonstrating seroconversion or a significant increase in antibody level, can aid in the diagnosis of primary infection with HSV. These reagents can be used either manually or in conjunction with the MAGO® Plus Automated EIA Processor.

Woody Dubois

ion of Clinical Laboratory Devices 510(k) Number

Regulation Number and Section

§ 866.3305 Herpes simplex virus serological assays.

(a)
Identification. Herpes simplex virus serological assays are devices that consist of antigens and antisera used in various serological tests to identify antibodies to herpes simplex virus in serum. Additionally, some of the assays consist of herpes simplex virus antisera conjugated with a fluorescent dye (immunofluorescent assays) used to identify herpes simplex virus directly from clinical specimens or tissue culture isolates derived from clinical specimens. The identification aids in the diagnosis of diseases caused by herpes simplex viruses and provides epidemiological information on these diseases. Herpes simplex viral infections range from common and mild lesions of the skin and mucous membranes to a severe form of encephalitis (inflammation of the brain). Neonatal herpes virus infections range from a mild infection to a severe generalized disease with a fatal outcome.(b)
Classification. Class II (special controls). The device is classified as class II (special controls). The special control for the device is FDA's revised guidance document entitled “Class II Special Controls Guidance Document: Herpes Simplex Virus Types 1 and 2 Serological Assays.” For availability of the guidance revised document, see § 866.1(e).