IMMULITE Herpes I & II IgG is designed for the qualitative detection of IgG antibodies to herpes simplex virus (HSV) type I & II in human serum. It is intended strictly for in vitro diagnostic use as an aid in the determination of serological status to HSV I & II.

Device Description

IMMULITE® Herpes I & II IgG is a solid-phase, two-step, chemiluminescent enzyme immunoassay. The solid phase, a polystyrene bead enclosed within an IMMULITE® Test Unit, is coated with a partially purified HSV I and II viral antigen.

AI/ML Overview

Here's an analysis of the provided text regarding the acceptance criteria and the study proving the device meets them:

1. A table of acceptance criteria and the reported device performance

The document does not explicitly state pre-defined acceptance criteria values for agreement, sensitivity, or specificity. Instead, it presents the performance of the IMMULITE Herpes I & II IgG assay and implicitly suggests a level of performance comparable to the predicate device and CDC results as acceptable.

Here's a table summarizing the reported performance, compared to what the document implies as acceptable by demonstrating substantial equivalence:

Performance Metric	Implied Acceptance Criterion (e.g., comparable to predicate/CDC)	Reported Device Performance (IMMULITE Herpes I & II IgG)	Study Context
Total Agreement	N/A (compared to CDC results)	97%	CDC Panel
Positive Agreement	N/A (compared to CDC results)	99%	CDC Panel
Negative Agreement	N/A (compared to CDC results)	93%	CDC Panel
Agreement	Comparable to BioWhittaker HSV ELISA II IgG	99.0% (Site 1), 96.0% (Site 2)	Method Comparison with Predicate
Relative Sensitivity	Comparable to BioWhittaker HSV ELISA II IgG	100.0% (Site 1), 96.2% (Site 2)	Method Comparison with Predicate
Relative Specificity	Comparable to BioWhittaker HSV ELISA II IgG	96.6% (Site 1), 94.9% (Site 2)	Method Comparison with Predicate

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

CDC Panel Study:
- Sample Size: Not explicitly stated as a number, but the panel consisted of "72% positive and 28% negative samples." To infer the total size, we would need the absolute number of positive or negative samples. However, the exact sample size for this specific test set is not provided in numerical terms.
- Data Provenance: United States Centers for Disease Control and Prevention (CDC), retrospective.
Method Comparison Study (with BioWhittaker):
- Sample Size:
  - Site 1: n = 200
  - Site 2: n = 202
- Data Provenance: "two independent sites," but the country of origin is not specified. The study was "nonconcurrently" conducted at these sites. The nature of the samples (e.g., patient samples, banked samples) is not detailed, but it tested the performance against the predicate device.

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

The document does not provide information on the number of experts used or their qualifications for establishing ground truth, for either the CDC panel or the method comparison studies.

For the CDC panel, it states the results were "obtained by IMMULITE" (which implies the DPC device) and then "sending the results to the CDC for unmasking." This suggests the CDC had their own "characterized" panel, but how that characterization (ground truth) was established, or by whom, is not detailed.

For the method comparison, the "ground truth" for the comparison was the results of the predicate device (BioWhittaker HSV ELISA II IgG).

4. Adjudication method for the test set

The document does not specify any adjudication method (e.g., 2+1, 3+1). For the CDC panel, it seems the ground truth was pre-established (a "masked, characterized serum panel") by the CDC. For the method comparison, the predicate device's results served as the reference for "relative" sensitivity and specificity, so no human adjudication method for disagreement is described.

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 automated immunoassay analyzer for detecting antibodies, not an AI-assisted diagnostic imaging or interpretation tool that would involve human readers.

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

Yes, a standalone study was done. The IMMULITE Herpes I & II IgG is an automated immunoassay system. The reported performance metrics (agreement, sensitivity, specificity) reflect the performance of the device itself (the "algorithm" in the context of an automated analyzer) without human interpretive intervention. The process involves introducing samples and buffers, incubation, and then the luminometer measures the photon output, which is then quantitatively compared to a cutoff to yield a qualitative result.

7. The type of ground truth used

CDC Panel Study: The ground truth was provided by the CDC as a "masked, characterized serum panel." The specific method of characterization (e.g., expert consensus, other established assays, clinical outcomes) is not detailed, beyond stating it was "characterized."
Method Comparison Study: The ground truth for calculating "relative sensitivity" and "relative specificity" was the results obtained from the predicate device, BioWhittaker HSV ELISA II IgG kit. This means the IMMULITE device's performance was compared against the predicate device, not necessarily against a definitive gold standard.

8. The sample size for the training set

The document does not mention or provide information about a specific "training set" or its size for the IMMULITE Herpes I & II IgG assay. This is typical for such diagnostic assays, where assay development and optimization (often referred to as "training" in AI contexts) are part of the manufacturer's internal process and not usually reported as a separate "training set" in regulatory submissions. The studies described are performance validation studies.

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

Since no "training set" is described in the context of this regulatory submission, there is no information on how its ground truth was established. Assay development usually involves internal validation against known positive and negative samples, often characterized through reference methods or clinical diagnosis, but these details are not provided here.

Summary

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Diagnostic Products Corporation 5700 West 96th Street
Los Angeles, CA 90045 Tel: (213) 776-0180 Fax: (213) 776-0204

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K950676

JUN 21 1906

510 (k) Summary 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 Part 807.92.

Name:	Diagnostic Products Corporation
Address:	5700 West 96th StreetLos Angeles, California 90045
Telephone Number:	(213) 776-0180
Facsimile Number:	(213) 776-0204
Contact Person:	Edward M. Levine, Ph.D.
Date of Preparation:	March 28, 1996
Device Name:	IMMULITE Herpes I & II IgG
Trade:	LKHSZ (50 tests); LKHS2 (200 tests)
Common:	Reagent system for the determination of Herpes I & II IgG antibodies in human serum.
Classification:	Class III device (866.3305)
Manufacturer:	EURO/DPC, a wholly-owned subsidiary of Diagnostic Products Corporation. (Manufacturing under a Quality System - ISO 9001/EN29001/BS 5750/part 1)
Establishment Registration #:	EURO/DPC: Not ApplicableDPC: 2017183
Substantially Equivalent Predicate Device:	BioWhittaker HSV ELISA II IgG (K822883)
Description of Device:	IMMULITE Herpes I & II IgG is a clinical device for use with the IMMULITE Automated Immunoassay Analyzer
Intended Use of the Device:	IMMULITE Herpes I & II IgG is designed for the qualitative detection of IgG antibodies to herpes simplex virus (HSV) type I & II in human serum. It is intended strictly for in vitro diagnostic use as an aid in the determination of serological status to HSV I & II.

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ostic Products Corporation Wast afith Street Fax: (213) 776-0204

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Summary and Explanation of the Test:

Herpes simplex virus (HSV) is an ancient and ubiquitous virus, known to cause and recurrent infections in humans. The virus enters the mucous membranes (ocular, genital, or oral) and replicates locally and may enter the sensory root ganglion, resulting in latent, recurrent infections. Infection of neonates during passage through the birth canal may result in neurological damage and death.

In the 1960s it was recognized that HSV consisted of two distinct types, HSV-II. HSV-I is considered to be primarily associated with ocular and oral infection, while HSV-II is considered to be a genital infection. However, HSV types I and II share several common antigens, and the use of specific monoclonal antibodies or restriction endonuclease mapping is required to type individual strains.

Infections with HSV type I or type II can differ in their clinical manifestations and severity. The immune response of the host can play an important role in controlling the severity of primary or reactivated infections. Those at highest risk for severe infections are neonates, who are infected during delivery, and immunocompromised patients.

While isolation of the virus in tissue culture is recommended for the diagnosis of active infections, serological testing can provide valuable information in the management of at-risk populations, such as pregnant women.

Summary and Explanation of the Device:

IMMULITE® Herpes I & II IgG is a solid-phase, two-step, chemiluminescent enzyme immunoassay.

The solid phase, a polystyrene bead enclosed within an IMMULITE® Test Unit, is coated with a partially purified HSV I and II viral antigen.

Prediluted patient sample (1-in-21 dilution: 1 part in a total of 21 parts) and a protein-based buffer are simultaneously introduced into the Test Unit, and incubated for approximately 30 minutes at 37°C with intermittent agitation. During this time, Herpes I and II IgG in the sample binds to the HSV I and II antigen-coated bead. Unbound serum is then removed by a centrifugal wash.
An alkaline phosphatase-labeled anti-human IgG antibody is introduced, and the Test Unit is incubated for another 30-minute cycle. The unbound enzyme conjugate is removed by a centrifugal wash. Substrate is then added, and the Test Unit is incubated for a further 10 minutes .

The chemiluminescent substrate, PPD (a phosphate ester of adamantyl dioxetane), undergoes hydrolysis in the presence of alkaline phosphatase to yield an unstable intermediate. The continuous production of this intermediate results in a sustained emission of light, thus improving precision by providing a window for multiple readings. The bound complex - and thus also the photon output, as measured by the luminometer - is related to the presence of HSV I and II IgG in the sample. A qualitative result is then obtained by comparing the patient result to an established Cutoff.

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Diagnostic Products Corporation 0 West 96th Street s Angeles, CA 90045 (213) 776-0180 Fax: (213) 776-0204

Performance Equivalence - Technology Comparison:

Diagnostic Products Corporation (DPC) asserts that IMMULITE® Herpes I & II IgG is substantially equivalent to the HSV ELISA II IgG kit marketed by BioWhittaker Inc.(Walkersville, MD).

Each product is designed for the detection of IgG antibodies to HSV I & II virus in human serum. Each product is intended strictly for in vitro diagnostic use as an aid in the determination of serological status to HSV I & II.

IMMULITE® Herpes I & II IgG is a chemiluminescent enzyme immunoassay and the HSV ELISA II IgG test is an enzyme-linked immunosorbent assay (ELISA). The technology in DPC's IMMULITE® Herpes I & II IgG is identical to technology used in previously cleared and commercially marketed IMMULITE® products.

In the BioWhittaker HSV ELISA II IgG assay, partially purified herpes antigen is attached to the surface of microplate wells. Diluted patient serum is added to the wells, and the herpes specific antibody, if present, binds to the antigen. All unbound antibody is washed away and enzyme-conjugated anti-human IgG is added. The enzyme conjugate binds to the antibody-antigen Excess enzyme conjugate is washed away and substrate is added. Bound enzyme complex. conjugate begins a hydrolytic reaction. After a specified time, the enzyme reaction is stopped. The intensity of the color generated is proportional to the amount of herpes IgG specific antibody in the sample. The results are read by a spectrophotometer, producing an indirect measurement of the herpes IgG specific antibody in the serum.

Performance Equivalence - Method Comparison:

The clinical performance of the IMMULITE Herpes I & II IgG assay was studied at Diagnostic Products Corporation (DPC) using a CMV/HSV proficiency panel obtained from the United States Centers for Disease Control and Prevention (CDC).

The in-house (DPC) retrospective study was conducted by assaying the CDC serum panel with the IMMULITE Herpes I & II IgG assay and sending the results to the CDC for unmasking. The results are presented as a means to convey further information on the performance of this assay with a masked, characterized serum panel. This does not imply an endorsement of the assay by the CDC.

The panel consisted of 72% positive and 28% negative samples. IMMULITE Herpes I & II IgG demonstrated 97% total agreement with the CDC results obtained by IMMULITE, there was 99% agreement with the positive specimens and 93% agreement with the negative results.

Studies on the clinical performance of the IMMULITE Herpes I & II IgG assay and the BioWhittaker HSV ELISA II IgG assay were also conducted nonconcurrently at two independent sites. A summary of the results is shown in the table below.

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Diagnostic Products Corporation 5700 West 96th Street Los Angeles, CA 90045
Tel: (213) 776-0180 Fax: (213) 776-0204

Image /page/3/Picture/1 description: The image shows the logo for DPC. The logo is in black and white and features the letters "DPC" in a bold, sans-serif font. The letters are connected to each other, and there is a registered trademark symbol to the right of the letter "C". The logo is simple and modern.

: $ 201

Performance Equivalence - Method Comparison (continued):

	IMMULITE vs.BioWhittaker (Site I)	IMMULITE vs.BioWhittaker (Site 2)
Agreement	99.0%	96.0%
Relative Sensitivity	100.0%	96.2%
Relative Specificity	96.6%	94.9%
n =	200	202

Conclusion:

The conclusions drawn from the clinical and nonclinical studies demonstrate that the device is safe, effective, and performs as well as, or better, than the current legally marketed devices.

Edward Levine

Edward M. Levine, Ph.D. Manager of Clinical Affairs

4/3/96

Date

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).