ELECSYS HSV-2 IGG IMMUNOASSAY

K121895 · Roche Diagnostics · JJX · Aug 24, 2012 · Clinical Chemistry

Device Facts

• Record ID: K121895
• Device Name: ELECSYS HSV-2 IGG IMMUNOASSAY
• Applicant: Roche Diagnostics
• Product Code: JJX · Clinical Chemistry
• Decision Date: Aug 24, 2012
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1660
• Device Class: Class 1

Intended Use

The Roche Elecsys HSV-2 IgG immunoassay is a test for the in vitro qualitative determination of IgG class antibodies to HSV-2 in human serum and lithium-heparin plasma, K2-EDTA plasma, and K3-EDTA plasma. The test is intended for sexually active individuals and expectant mothers as an aid in presumptive diagnosis of HSV-2 infection. The predictive value of positive or negative results depends on the population's prevalence and the pretest likelihood of HSV-2. The electrochemiluminescence immunoassay "ECLIA" is intended for use on the indicated Elecsys and cobas e immunoassay analyzers. This test is not FDA cleared for screening blood or plasma donors. The performance of this assay has not been established for use in a pediatric population, neonates and immunocompromised patients or for use at point of care facilities. The Elecsys PreciControl HSV is used for quality control of the Elecsys HSV-2 IgG immunoassay on the Elecsys and cobas e immunoassay analyzers.

Device Story

Elecsys HSV-2 IgG is a two-step sandwich immunoassay using streptavidin microparticles and biotinylated recombinant HSV-2-specific antigen labeled with a ruthenium complex. Device utilizes electrochemiluminescence (ECLIA) detection on Elecsys and cobas e immunoassay analyzers. Input is human serum or plasma (lithium-heparin, K2-EDTA, K3-EDTA). System performs automated calculation of cut-off index (COI) based on two-point calibration using negative and positive calibrators. Output is qualitative (reactive/non-reactive) based on COI >= 1.0. Used in clinical laboratories by trained personnel. Results aid physicians in presumptive diagnosis of HSV-2 infection when correlated with clinical history and symptoms. Benefits include automated, standardized testing compared to manual methods.

Clinical Evidence

Clinical performance evaluated across three cohorts: expectant mothers (n=125), sexually active individuals (n=469), and low prevalence population (n=200). Positive percent agreement ranged from 75.00% to 97.83%; negative percent agreement ranged from 98.47% to 98.73%. Agreement with CDC panel was 100%. Analytical specificity tested against 13 cross-reactants with 100% agreement.

Technological Characteristics

Two-step sandwich immunoassay; electrochemiluminescence detection. Reagents: streptavidin-coated microparticles, biotinylated recombinant HSV-2 antigen (E. coli), ruthenylated HSV-2 antigen. Automated platform (Elecsys/cobas e series). Calibration: two-point, lot-specific. Controls: lyophilized human serum-based. Connectivity: integrated with analyzer software.

Indications for Use

Indicated for sexually active individuals and expectant mothers as an aid in presumptive diagnosis of HSV-2 infection. Not for pediatric, neonatal, immunocompromised patients, or point-of-care use. Not for blood/plasma donor screening.

Regulatory Classification

Identification

A quality control material (assayed and unassayed) for clinical chemistry is a device intended for medical purposes for use in a test system to estimate test precision and to detect systematic analytical deviations that may arise from reagent or analytical instrument variation. A quality control material (assayed and unassayed) may be used for proficiency testing in interlaboratory surveys. This generic type of device includes controls (assayed and unassayed) for blood gases, electrolytes, enzymes, multianalytes (all kinds), single (specified) analytes, or urinalysis controls.

Submission Summary (Full Text)

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# 510(k) Summary

K121895.

AUG 2 4 2012

| Introduction | According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence. |
|----------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Submitter Name, Address, Contact | Roche Diagnostics<br>9115 Hague Road<br>P.O. Box 50416<br>Indianapolis, IN 46250-0416<br>Phone: [phone]<br>Fax: [phone] |
| | Contact Person: K. Colleen Adams, Regulatory Affairs Principal<br>Date Prepared: June 27, 2012 |
| Device Name | |
| | Proprietary name: (1) Elecsys HSV-2 IgG Immunoassay<br>(2) Elecsys PreciControl HSV |
| | Common name: (1) HSV-2 IgG<br>(2) PreciControl HSV |
| | Classification name: (1) Class 2, 21 CFR 866.3305, Herpes simplex virus serological assays<br>(2) Class 1, 21 CFR 862.1660, Quality control material (assayed and unassayed) |
| | Product Code: MYF, JJX |
| | Predicate Device: Focus HerpeSelect 1 and 2 Immunoblot IgG (K000238) |
| | Continued on next page |

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#### Device Description

(1) Elecsys HSV-2 IgG is a two-step sandwich immunoassay with streptavidin microparticles, biotinylated recombinant HSV-2-specific antigen labeled with a ruthenium complex and electrochemiluminescence detection. This assay is a qualitative test based on a cut-off formula dependent on the negative and positive calibrators. Cut-off index (COI) is based on the ratio of assay signal to cut-off signal (also abbreviated s/co). COI values greater than or equal to 1.0 are considered positive for the presence of anti-HSV-2 IgG antibody. Results are determined using a two-point calibration. The test system contains the human serum-based calibrators intended for use with the system.

(2) Elecsys PreciControl HSV contains lyophilized control serum based on human serum. The controls are used for monitoring the accuracy of the Elecsys HSV-2 IgG immunoassay.

Note: The reagent and calibrators are packaged together in the Elecsys HSV-2 IgG assay, while the associated PreciControl is packaged separately.

| Intended<br>Use/Indications<br>for Use | Elecsys HSV-2 IgG Immunoassay: | |
|----------------------------------------|------------------------------------------------------------------------------|--|
| | The Roche Elecsys HSV-2 IgG immunoassay is a test for the <i>in vitro</i> | |
| | qualitative determination of IgG class antibodies to HSV-2 in human serum | |
| | and lithium-heparin plasma, K2-EDTA plasma, and K3-EDTA plasma. The | |
| | test is intended for sexually active individuals and expectant mothers as an | |
| | aid in presumptive diagnosis of HSV-2 infection. The predictive value of | |
| | positive or negative results depends on the population's prevalence and the | |
| | pretest likelihood of HSV-2. The electrochemiluminescence immunoassay | |
| | "ECLIA" is intended for use on the indicated Elecsys and cobas e | |
| | immunoassay analyzers. | |

This test is not FDA cleared for screening blood or plasma donors.

The performance of this assay has not been established for use in a pediatric population, neonates and immunocompromised patients or for use at point of care facilities.

#### Elecsys PreciControl HSV:

The Elecsys PreciControl HSV is used for quality control of the Elecsys HSV-2 IgG immunoassay on the Elecsys and cobas e immunoassay analyzers.

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The Elecsys HSV-2 IgG immunoassay test system is substantially Substantial Equivalence equivalent to other devices legally marketed in the United States. (1) Elecsys HSV-2 IgG Immunoassay is equivalent to HerpeSelect 1 and 2 Immunoblot, MRL/Focus Diagnostics (K000238). (2) Elecsys PreciControl HSV is equivalent to the Elecsys PreciControl Anti-CCP (K081338). 1999 - 1999 The following tables compare the Elecsys HSV-2 IgG immunoassay Substantial and PreciControl HSV with their respective predicate devices. Equivalence -Comparison

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| Immunoassay Comparison | | |
|---------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Feature | Elecsys HSV-2 IgG Immunoassay<br>(Candidate Device) | Focus HerpeSelect 1&2<br>(Predicate Device: K000238) |
| | General Assay Features | |
| Intended Use/<br>Indications for Use | The Roche Elecsys HSV-2 IgG<br>immunoassay is a test for the <i>in vitro</i><br>qualitative determination of IgG class<br>antibodies to HSV-2 in human serum<br>and lithium-heparin plasma, K2 -<br>EDTA plasma, and K3-EDTA plasma.<br>The test is intended for sexually active<br>individuals and expectant mothers as<br>an aid in presumptive diagnosis of<br>HSV-2 infection. The predictive value<br>of positive or negative results depends<br>on the population's prevalence and the<br>pretest likelihood of HSV-2.<br><br>The electrochemiluminescence<br>immunoassay “ECLIA” is intended<br>for use on the indicated Elecsys and<br>cobas e immunoassay analyzers.<br><br>The test is not FDA cleared for<br>screening blood or plasma donors.<br><br>The performance of this assay has not<br>been established for use in a pediatric<br>population, neonates and<br>immunocompromised patients or for<br>use at point of care facilities. | Focus Diagnostics' HerpeSelect 1 and<br>2 Immunoblot IgG test is intended for<br>qualitatively detecting the presence or<br>absence of human IgG class antibodies<br>to HSV-1 and HSV-2 in human sera.<br>The test is indicated for testing<br>sexually active adults or expectant<br>mothers for aiding in the presumptive<br>diagnosis of HSV-1 and HSV-2<br>infection. The predictive value of a<br>positive or negative result depends on<br>the population's prevalence and the<br>pretest likelihood of HSV-1 and HSV-<br>2 infection. The performance of this<br>assay has not been established for use<br>in a pediatric population, for neonatal<br>screening, for testing of<br>immunocompromised patients, for use<br>by a point of care facility or for use<br>with automated equipment. |
| Assay<br>Protocol | Sandwich assay | Nitrocellulose immunoblot |
| Detection<br>Protocol | Electrochemiluminescent<br>Immunoassay | Alkaline phosphatase (qualitative) |
| Applications | 18 minutes | Manual procedure |
| Immunoassay Comparison | | |
| Feature | Elecsys HSV-2 IgG Immunoassay<br>(Candidate Device) | Focus HerpeSelect 1&2<br>(Predicate Device: K000238) |
| Instrument<br>Platform | Elecsys 2010, MODULAR<br>ANALYTICS E170, cobas e 411,<br>cobas e 601, and cobas e 602 | Manual procedure |
| Sample<br>Volume | 20 µL | 20 µL |
| Sample<br>Type | Human serum and Lithium-heparin,<br>K2-EDTA, and K3-EDTA plasma | Human serum |
| Reagents | Reagents consist of streptavidin-<br>coated microparticles, biotinylated<br>HSV-2 antigen (recombinant, from E.<br>coli), ruthenylated HSV-2 antigen and<br>negative and positive calibrators. | Reagents consist of HSV-1 and HSV-<br>2 differentiation antigen strips,<br>alkaline phosphatase-conjugated goat<br>anti-human IgG, bromo-chloro-<br>indodyl phosphate and nitroblue<br>tetrazolium substrate and negative and<br>positive controls. |
| Calibrator | Included with the reagent kit | Not included with this qualitative test |
| Calibration<br>Interval | Calibration must be performed once<br>per reagent lot using fresh reagent (i.e.<br>not more than 24 hours since the<br>reagent kit was registered on the<br>analyzer). Renewed calibration is<br>recommended as follows:<br>• After 1 month (28 days) when<br>using the same reagent lot.<br>• After 7 days (when using the same<br>reagent kit on the analyzer).<br>• As required: e.g. quality control<br>findings outside the specified<br>limits | Calibrators are not included for this<br>qualitative assay. Negative and<br>positive controls are run with every<br>test. |
| Immunoassay Comparison | | |
| Feature | Elecsys HSV-2 IgG Immunoassay<br>(Candidate Device) | Focus HerpeSelect 1&2<br>(Predicate Device: K000238) |
| General Assay Features | | |
| Controls | Elecsys PreciControl HSV | Negative and positive controls are<br>included with the Focus kit. |
| Traceability /<br>Standardizati<br>on | The Elecsys HSV-2 IgG<br>immunoassay has been standardized<br>a Roche standard. The units have<br>been selected arbitrarily. | There is no standardization for this<br>qualitative assay. |
| Reagent<br>Stability | Reagents, ready to use:<br>2-8°C – Up to the stated expiration<br>date<br>After opening at 2-8°C – 8 weeks<br>On the analyzers – 21 days<br><br>Calibrators (lyophilized):<br>Unopened at 2-8°C – Up to stated<br>expiration date<br>After reconstitution at 2-8°C – 14<br>days<br>On the Elecsys 2010 and cobas e 411<br>20-25°C – Up to 5 hours<br>On the MODULAR ANALYTICS<br>E170, cobas e 601, and cobas e 602<br>– Use only once | Kits and reagents are stable through<br>the end of the month indicated on their<br>expiration dates when stored at 2-8°C. |
| Cutoffs | The analyzer automatically calculates<br>the cutoff based on the measurement<br>of Cal 1 and Cal 2. The result of a<br>sample is given either as reactive or<br>non-reactive as well as in the form of<br>a cutoff index. | Positive or negative results are<br>generated by this qualitative assay by<br>comparing bands on the nitrocellulose<br>to a cut-off/control strip. |
| Immunoassay Comparison | | |
| Feature | Elecsys HSV-2 IgG Immunoassay<br>(Candidate Device) | Focus HerpeSelect 1&2<br>(Predicate Device: K000238) |
| | General assay features | |
| Cutoffs<br>(continued) | For the Elecsys HSV-2 IgG<br>immunoassay, the interpretation of the<br>results is: | |
| | Non-reactive < $1.0$ COI<br>Reactive ≥ $1.0$ COI | |
| Result<br>Interpretation | Samples with a cutoff index < $1.0$ are<br>non-reactive in the Elecsys HSV-2<br>IgG assay. These samples are<br>considered negative for HSV-2 IgG-<br>specific antibodies and do not need<br>further testing. Samples with a cutoff<br>index of ≥ $1.0$ are considered reactive<br>in the Elecsys HSV-2 IgG assay. | Compare each band on a strip<br>relative to the reading control band.<br>The reading control band is the IgG-<br>2 band on the Cutoff/Positive<br>Control strip. If the band is as dark,<br>or darker than the reading control<br>band, then the band is reactive (+).<br>Likewise, if the band is lighter than<br>the reading control band, then the<br>band is unreactive (neg.). The<br>overall band reactivity is then used<br>to interpret results. |
| Limits of<br>Measurement | LoB = $0.11$ COI<br>LoD = $0.1244$ COI | Not applicable to this qualitative<br>test |
| Hook Effect | No hook effect up to $10$ COI | Not tested |

### Comparison of Assays—Similarities and Differences

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#### Comparison of Assays—Similarities and Differences i

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| Immunoassay Comparison | | |
|------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Feature | Elecsys HSV-2 IgG Reagent and<br>Calibrator<br>(Candidate Device) | Focus HerpeSelect 1&2<br>(Predicate Device: K000238) |
| | Labeled Performance Characteristics | |
| Precision | Intra-assay:<br>Low Control: SD 0.005 COI<br>High Control: CV 1.3%<br>Serum Samples < 0.8 COI:<br>SD 0.001 - 0.004 COI<br>Serum Samples > 0.8 COI:<br>CV 1.2 - 1.6%<br>Inter-assay:<br>Low Control: SD 0.010 COI<br>High Control: CV 3.3%<br>Serum Samples < 0.8 COI:<br>SD 0.002 - 0.007 COI<br>Serum Samples > 0.8 COI:<br>CV 2.8 - 3.6% | Inter Laboratory Reproducibility: An<br>internal investigator and 2 external<br>laboratories assessed the device's<br>reproducibility. Seven samples were<br>run in triplicate on 3 different days.<br>Using the Focus Elisa Index (negative<br>if less than 0.90, equivocal if between<br>0.90 and 1.10, and positive if greater<br>than 1.10) the manufacturer was able<br>to demonstrate 100% agreement with<br>intra-assay, inter-assay, inter-lot and<br>inter-lab precision testing. |

### Comparison of Assays-Similarities and Differences, continued

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| Immunoassay Comparison | | |
|-------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Feature | Elecsys HSV-2 IgG Immunoassay<br>(Candidate Device) | Focus HerpeSelect 1&2<br>(Predicate Device: K000238) |
| Labeled Performance Characteristics | | |
| Analytical<br>Specificity | 311 HSV-2-negative specimens,<br>which were positive for the following<br>cross reactants, were tested with the<br>Elecsys HSV-2 IgG and the<br>comparator assay: Antinuclear<br>antibodies, Varicella zoster virus,<br>Human indefficiency virus,<br>Cytomegalovirus, Neisseria<br>gonorrhea, Toxoplasma gondi,<br>Chlamydia trachomatis, Candida<br>albicans, Epstein Barr virus, Rubella,<br>E. Coli, HSV-1, and Treponema<br>pallidum. 100% agreement was<br>demonstrated between the two assays. | The sponsor tested 32 HSV negative<br>samples which were positive for<br>Cytomegalovirus, Epstein Barr virus,<br>Virus Capsid antigen, Human<br>herpesvirus6 or Varicella zoster virus.<br>Eight of the samples were found to be<br>positive with the Focus Immunoblot,<br>while the 24 remaining samples were<br>negative. |

### Comparison of Assays-Similarities and Differences, continued

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| Comparison of Assays-Similarities and Differences, continued | | |
|--------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Immunoassay Comparison | | |
| Feature | Elecsys HSV-2 IgG Immunoassay<br>(Candidate Device) | Focus HerpeSelect 1&2<br>(Predicate Device: K000238) |
| | Labeled Performance Characteristics |…