← Product Code [MYF](/submissions/MI/subpart-d%E2%80%94serological-reagents/MYF) · K243575

# ARCHITECT HSV-2 IgG, ARCHITECT HSV-2 IgG Calibrator, ARCHITECT HSV-2 IgG Controls (K243575)

_Biokit, S.A. · MYF · Feb 12, 2025 · Microbiology · SESE_

**Canonical URL:** https://fda.innolitics.com/submissions/MI/subpart-d%E2%80%94serological-reagents/MYF/K243575

## Device Facts

- **Applicant:** Biokit, S.A.
- **Product Code:** [MYF](/submissions/MI/subpart-d%E2%80%94serological-reagents/MYF.md)
- **Decision Date:** Feb 12, 2025
- **Decision:** SESE
- **Submission Type:** Traditional
- **Regulation:** 21 CFR 866.3305
- **Device Class:** Class 2
- **Review Panel:** Microbiology

## Indications for Use

The ARCHITECT HSV-2 IgG assay is a chemiluminescent microparticle immunoassay (CMIA) used for the qualitative detection of specific IgG antibodies to herpes simplex virus type 2 (HSV-2) in human serum (collected in serum and serum separator tubes) and plasma (collected in dipotassium EDTA, lithium heparin, and lithium heparin plasma separator tubes) on the ARCHITECT i System. The ARCHITECT HSV-2 IgG assay is to be used for testing sexually active adults or expectant mothers to aid in the presumptive diagnosis of HSV-2 infection. The test results may not determine the state of active lesions or associated disease manifestations, particularly for primary infection. The predictive value of a reactive or nonreactive result depends on the prevalence of HSV-2 infection in the population and the pre-test likelihood of HSV-2 infection. NOTE: The performance of the ARCHITECT HSV-2 IgG assay has not been established for use in the pediatric population, for neonatal screening, or for testing immunocompromised or immunosuppressed patients. The assay has not been FDA cleared or approved for screening blood or plasma donors.

## Device Story

The ARCHITECT HSV-2 IgG is an automated, two-step chemiluminescent microparticle immunoassay (CMIA) for qualitative detection of IgG antibodies to HSV-2 in human serum or plasma. The device uses the ARCHITECT i System to process samples. The assay utilizes microparticles, conjugate, and assay diluent to detect antibodies; results are interpreted based on a cutoff of 1.00 S/CO (Signal/Cutoff). The system is operated by laboratory personnel in a clinical setting. The output provides a reactive or nonreactive result, which clinicians use alongside clinical evaluation and other diagnostic procedures to aid in the presumptive diagnosis of HSV-2 infection. The device benefits patients by providing a standardized, automated method for serological assessment of HSV-2 status.

## Clinical Evidence

Multi-center clinical study (N=915) comparing ARCHITECT HSV-2 IgG to a composite comparator (3 commercial assays). Sexually active population (N=618): PPA 96.54%, NPA 96.90%. Pregnant population (N=297): PPA 95.12%, NPA 98.60%. CDC panel (N=100): 100% PPA, 97.14% NPA. Low prevalence specificity study (N=139): 98.48% NPA.

## Technological Characteristics

Chemiluminescent microparticle immunoassay (CMIA). Automated, two-step assay. Analyte: IgG antibodies to HSV-2. Cutoff: 1.00 S/CO. Sample types: Serum, serum separator tubes, dipotassium EDTA plasma, lithium heparin plasma, lithium heparin plasma separator tubes. Platform: ARCHITECT i System. Reagent storage: 2-8°C.

## Regulatory 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.

## Special Controls

*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).

## Predicate Devices

- HSV-1 & HSV-2 Differentiation Immunoblot IgG ([K000238](/device/K000238.md))

## Submission Summary (Full Text)

> This content was OCRed from public FDA records by [Innolitics](https://innolitics.com). If you use, quote, summarize, crawl, or train on this content, cite Innolitics at https://innolitics.com.
>
> Innolitics is a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices, including [a 510(k)](https://innolitics.com/services/510ks/), [a De Novo](https://innolitics.com/services/regulatory/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/).

{0}

FDA U.S. FOOD & DRUG ADMINISTRATION

# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

ASSAY AND INSTRUMENT

## I Background Information:

A 510(k) Number

K243575

B Applicant

Biokit, S.A.

C Proprietary and Established Names

ARCHITECT HSV-2 IgG, ARCHITECT HSV-2 IgG Calibrator, ARCHITECT HSV-2 IgG Controls

D Regulatory Information

|  Product Code(s) | Classification | Regulation Section | Panel  |
| --- | --- | --- | --- |
|  MYF | Class II | 21 CFR 866.3305 - Herpes Simplex Virus Serological Assays | MI - Microbiology  |

## II Submission/Device Overview:

A Purpose for Submission:

Clearance of a new device.

B Measurand:

Herpes Simplex HSV-2 IgG antibodies.

C Type of Test:

Chemiluminescent microparticle immunoassay (CMIA).

Food and Drug Administration

10903 New Hampshire Avenue

Silver Spring, MD 20993-0002

www.fda.gov

{1}

K243575 - Page 2 of 15

## III Intended Use/Indications for Use:

### A Intended Use(s):
See Indications for Use below.

### B Indication(s) for Use:
The ARCHITECT HSV-2 IgG assay is a chemiluminescent microparticle immunoassay (CMIA) used for the qualitative detection of specific IgG antibodies to herpes simplex virus type 2 (HSV-2) in human serum (collected in serum and serum separator tubes) and plasma (collected in dipotassium EDTA, lithium heparin, and lithium heparin plasma separator tubes) on the ARCHITECT i System.

The ARCHITECT HSV-2 IgG assay is to be used for testing sexually active adults or expectant mothers to aid in the presumptive diagnosis of HSV-2 infection. The test results may not determine the state of active lesions or associated disease manifestations, particularly for primary infection. The predictive value of a reactive or nonreactive result depends on the prevalence of HSV-2 infection in the population and the pre-test likelihood of HSV-2 infection.

NOTE: The performance of the ARCHITECT HSV-2 IgG assay has not been established for use in the pediatric population, for neonatal screening, or for testing immunocompromised or immunosuppressed patients. The assay has not been FDA cleared or approved for screening blood or plasma donors.

### C Special Conditions for Use Statement(s):
Rx - For Prescription Use Only

### D Special Instrument Requirements:
For use with the ARCHITECT i2000SR System.

## IV Device/System Characteristics:

### A Device Description:
The ARCHITECT HSV-2 IgG assay is an automated, two-step immunoassay for the qualitative detection of IgG antibodies to HSV-2 in human serum and plasma using chemiluminescent microparticle immunoassay (CMIA) technology.

The kit contains different components: Reagent (microparticles, conjugate and assay diluent), Calibrator, and external Controls (reactive and nonreactive).

**Interpretation of results**

The cutoff is 1.00 S/CO.

The ARCHITECT HSV-2 IgG test result should be used in conjunction with information available from clinical evaluation and other diagnostic procedures.

{2}

|  S/CO | Interpretation  |
| --- | --- |
|  < 1.00 | Nonreactive  |
|  ≥ 1.00 | Reactive  |

## B Principle of Operation:

The specimen is incubated with the assay diluent and microparticles which contain specific recombinant-gG2 antigen. Antigen-antibody complexes will form if anti-HSV-2 antibodies are present in the sample. The mixture is washed, and the unbound material is removed. The conjugate contains monoclonal anti-human IgG labeled with acridinium-labeled, and is used to detect HSV-2 IgG in the patient specimen. Anti-human IgG acridinium-labeled conjugate is added to create a reaction mixture and incubated. Following a wash cycle, Pre-Trigger and Trigger Solutions are added.

The resulting chemiluminescent reaction is measured as a relative light unit (RLU). There is a direct relationship between the amount of HSV-2 IgG detected in the sample and the RLU measured by the system optics.

The presence or absence of HSV-2 IgG in the sample is determined by comparing the chemiluminescent RLU measured to the cutoff RLU determined from an active calibration.

## C Instrument Description Information:

1. Instrument Name:
ARCHITECT i2000SR System

2. Specimen Identification:
|  Specimen Types | Collection Tubes  |
| --- | --- |
|  Serum | Serum
Serum separator  |
|  Plasma | Dipotassium EDTA
Lithium heparin
Lithium heparin separator  |

## V Substantial Equivalence Information:

A Predicate Device Name(s):
HSV-1 &amp; HSV-2 Differentiation Immunoblot IgG

B Predicate 510(k) Number(s):
K000238

K243575 - Page 3 of 15

{3}

C Comparison with Predicate(s):

|  Device & Predicate Device(s): | Predicate Device | Candidate Device  |
| --- | --- | --- |
|   |  K000238 | K243575  |
|  Device Trade Name | HSV-1 & HSV-2 Differentiation Immunoblot IgG | ARCHITECT HSV-2 IgG, ARCHITECT HSV-2 IgG Calibrator, ARCHITECT HSV-2 IgG Controls  |
|  General Device Characteristic Similarities |  |   |
|  Intended Use/Indications For Use | MRL Diagnostics' HSV-1 & HSV-2 Differentiation Immunoblot IgG test is intended for qualitatively detecting the presence or absence of human IgG class antibodies to HSV-1 and HSV-2 in human sera. The test is indicated for testing sexually active adults or expectant mothers for aiding in the presumptive diagnosis of HSV-1 and HSV-2 infection. The predictive value of a positive or negative result depends on the population's prevalence and pretest likelihood of HSV-1 and HSV-2 infection. The performance of this assay has not been established for use in a pediatric population, for neonatal screening, for testing of immunocompromised patients, for use by a point of care facility or for use with automated equipment. | The ARCHITECT HSV-2 IgG assay is a chemiluminescent microparticle immunoassay (CMIA) used for the qualitative detection of specific IgG antibodies to herpes simplex virus type 2 (HSV-2) in human serum (collected in serum and serum separator tubes) and plasma (collected in dipotassium EDTA, lithium heparin, and lithium heparin plasma separator tubes) on the ARCHITECT i System. The ARCHITECT HSV-2 IgG assay is to be used for testing sexually active adults or expectant mothers to aid in the presumptive diagnosis of HSV-2 infection. The test results may not determine the state of active lesions or associated disease manifestations, particularly for primary infection. The predictive value of a reactive or nonreactive result depends on the prevalence of HSV-2 infection in the population and the pre-test likelihood of HSV-2 infection. NOTE: The performance of the ARCHITECT HSV-2 IgG assay has not been established for use in the pediatric population, for neonatal screening, or for testing immunocompromised or immunosuppressed patients. The assay has not been FDA cleared or approved for screening blood or plasma donors.  |
|  Analyte | Human IgG class antibodies to HSV-1 and HSV-2 | Human IgG antibodies to HSV-2  |

K243575 - Page 4 of 15

{4}

|  Test type | Qualitative | Same  |
| --- | --- | --- |
|  Regulation Section | 21 CFR 866.3305 | Same  |
|  Classification | Class II Special Controls | Same  |
|  General Device Characteristic Differences |  |   |
|  Product Code | LGC | MYF  |
|  Technology | Nitrocellulose immunoblot | Chemiluminescent Immunoassay  |
|  Sample type | Human serum | Human serum (collected in serum and serum separator tubes) and plasma (collected in dipotassium EDTA, lithium heparin, and lithium heparin plasma separator tubes)  |
|  Interpretation | Visually evaluate multiple bands | The cutoff is 1.00 S/CO.
<1.00 S/CO = Nonreactive
≥1.00 S/CO = Reactive  |

VI Standards/Guidance Documents Referenced:

- CLSI EP05-A3 Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline -Third Edition (2014).
- CLSI EP07 Interference Testing in Clinical Chemistry; Approved Guideline-Third Edition (2018).
- CLSI EP09c Measurement Procedure Comparison and Bias Estimation Using Patient Samples. 3rd Edition (2018)
- CLSI EP12-A2 User Protocol for Evaluation of Qualitative Test Performance; Approved Guideline - Second Edition (2008).
- CLSI EP25-A Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline (2009).
- IEC/EN 61010-1:2010 (3rd Ed) Safety Requirements for Electrical Equipment for Measurement Control and Laboratory Use-Part 1
- CLSI I/LA21-A2 Clinical Evaluation of Immunoassays; Approved Guideline - Second Edition
- Class II Special Controls Guidance Document: Herpes Simplex Virus Types 1 and 2 Serological Assays

VII Performance Characteristics (if/when applicable):

A Analytical Performance:

1. Precision/Reproducibility:

a. Within-Laboratory Precision (20-Day).

A within laboratory precision study was performed using 3 lots of the ARCHITECT HSV-2 IgG reagents, 3 lots of the ARCHITECT HSV-2 IgG Calibrator, 1 lot of the ARCHITECT HSV-2 IgG controls, and 1 ARCHITECT i200SR instrument. The

K243575 - Page 5 of 15

{5}

performance of the 3 lots of the ARCHITECT HSV-2 IgG reagents is shown in the following tables.

Table 1: 20-Day Within-Laboratory Precision.

|  Sample | n | Mean (S/CO) | Within-Run (Repeatability) |   | Between-Lota |   | Within-Laboratoryb  |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |   |  SD | %CV | SD | %CV | SD | %CV  |
|  Negative Control | 240 | 0.30 | 0.009 | N/A | 0.007 | N/A | 0.012 | N/A  |
|  Positive Control | 240 | 3.01 | 0.075 | 2.5 | 0.081 | 2.7 | 0.117 | 3.9  |
|  Serum Panel 1 | 240 | 0.95 | 0.029 | N/A | 0.015 | N/A | 0.040 | N/A  |
|  Serum Panel 2 | 240 | 1.60 | 0.037 | 2.3 | 0.096 | 6.0 | 0.109 | 6.8  |
|  Serum Panel 3 | 244c | 2.47 | 0.093 | 3.7 | 0.270 | 10.9 | 0.286 | 11.6  |
|  Plasma Panel 1 | 240 | 1.03 | 0.028 | 2.7 | 0.004 | 0.4 | 0.034 | 3.3  |
|  Plasma Panel 2 | 240 | 1.81 | 0.047 | 2.6 | 0.089 | 4.9 | 0.103 | 5.7  |
|  Plasma Panel 3 | 240 | 2.91 | 0.071 | 2.4 | 0.093 | 3.2 | 0.126 | 4.3  |

$\mathrm{N / A} =$  Not applicable
a Calibrator and reagent lots are confounded.
b Includes within-run, between-run, between-day, and between-lot variability.
Serum Panel 3 was tested for one additional day.

# b. Within-Laboratory Precision (12-Day).

An additional within-laboratory precision study was conducted using samples with higher analyte levels, using 2 lots of the ARCHITECT HSV-2 IgG reagents, 1 lot of the ARCHITECT HSV-2 IgG Calibrator, and 1 ARCHITECT i2000SR instrument.

Table 2: 12-Day Within-Laboratory Precision.

|  Sample | n | Mean (S/CO) | Within-Run (Repeatability) |   | Between-Lot |   | Within-Laboratorya  |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |   |  SD | %CV | SD | %CV | SD | %CV  |
|  Serum Panel 4 | 96 | 7.14 | 0.274 | 3.8 | 0.125 | 1.7 | 0.372 | 5.2  |
|  Serum Panel 5 | 96 | 14.73 | 0.519 | 3.5 | 0.099 | 0.7 | 0.680 | 4.6  |
|  Plasma Panel 4 | 96 | 7.85 | 0.312 | 4.0 | 0.000 | 0.0 | 0.354 | 4.5  |
|  Plasma Panel 5 | 96 | 14.90 | 0.578 | 3.9 | 0.000 | 0.0 | 0.745 | 5.0  |

a Includes within-run, between-run, between-day, and between-lot variability.

K243575 - Page 6 of 15

{6}

c. Reproducibility.

A reproducibility study was conducted at 3 testing sites using one lot of the ARCHITECT HSV-2 IgG reagents, 1 lot of the ARCHITECT HSV-2 IgG Calibrator, 1 lot of the ARCHITECT HSV-2 IgG controls, and 1 ARCHITECT i2000SR instrument, over 5 days.

Table 3: Reproducibility.

|  Sample | N | Mean (S/CO) | Repeatability |   | Between-Run |   | Between-Day |   | Between-Site/Instrument |   | Reproducibilitya  |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |   |  SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV  |
|  Negative Control | 90 | 0.29 | 0.01 | N/A | 0.00 | N/A | 0.00 | N/A | 0.01 | N/A | 0.02 | N/A  |
|  Positive Control | 90 | 2.98 | 0.07 | 2.3 | 0.04 | 1.2 | 0.04 | 1.4 | 0.13 | 4.3 | 0.16 | 5.2  |
|  Serum Panel 1 | 90 | 0.89 | 0.02 | N/A | 0.01 | N/A | 0.01 | N/A | 0.02 | N/A | 0.04 | N/A  |
|  Serum Panel 2 | 90 | 1.56 | 0.05 | 3.5 | 0.00 | 0.0 | 0.01 | 0.7 | 0.03 | 2.0 | 0.06 | 4.0  |
|  Serum Panel 3 | 90 | 2.52 | 0.06 | 2.2 | 0.03 | 1.3 | 0.02 | 1.0 | 0.08 | 3.3 | 0.11 | 4.3  |
|  Plasma Panel 1 | 90 | 0.96 | 0.03 | N/A | 0.01 | N/A | 0.02 | N/A | 0.03 | N/A | 0.05 | N/A  |
|  Plasma Panel 2 | 90 | 1.76 | 0.05 | 2.8 | 0.00 | 0.0 | 0.03 | 1.7 | 0.07 | 4.0 | 0.09 | 5.2  |
|  Plasma Panel 3 | 90 | 2.82 | 0.09 | 3.3 | 0.00 | 0.0 | 0.00 | 0.0 | 0.12 | 4.3 | 0.15 | 5.4  |

a Includes repeatability (within-run), between-run, between-day, and between-instrument/site variability.

2. Linearity:

Not applicable.

3. Analytical Specificity/Interference:

a. Interference

Potentially Interfering Endogenous Substances and Potentially Interfering Drugs. The ARCHITECT HSV-2 IgG assay was evaluated for potential interference of endogenous and exogenous (drugs) substances using HSV-2 IgG nonreactive and low reactive samples.

K243575 - Page 7 of 15

{7}

Less than 10% absolute difference for reactive HSV-2 IgG samples and less than 0.10 S/CO absolute difference for nonreactive HSV-2 IgG samples were observed at the following concentrations of potentially interfering substances.

Table 4: Potentially Interfering Endogenous Substances.

|  Potentially Interfering Endogenous Substance | Potential Interferent Concentration  |   |
| --- | --- | --- |
|   |  Default Units | Alternate Units  |
|  Bilirubin (Conjugated) | 40 mg/dL | 475 μmol/L  |
|  Bilirubin (Unconjugated) | 40 mg/dL | 684 μmol/L  |
|  Hemoglobin | 1000 mg/dL | 10 g/L  |
|  Triglycerides | 1500 mg/dL | 16.94 mmol/L  |
|  Total Protein | 15 g/dL | 150 g/L  |
|  Serum Albumin | 6 g/dL | 60 g/L  |
|  Total Cholesterol | 400 mg/dL | 10.3 mmol/L  |

Table 5: Potentially Interfering Drugs.

|  Potentially Interfering Drug | Potential Interferent Concentration  |   |
| --- | --- | --- |
|   |  Default Units | Alternate Units  |
|  Acetaminophen | 15.6 mg/dL | 1030 μmol/L  |
|  Acetylsalicylic acid | 3.00 mg/dL | 167 μmol/L  |
|  Acyclovir | 6.6 mg/dL | 293 μmol/L  |
|  Ampicillin | 7.5 mg/dL | 215 μmol/L  |
|  Ascorbic acid | 5.25 mg/dL | 298 μmol/L  |
|  Biotin | 4250 ng/mL | 17.3 μmol/L  |
|  Calcium dobesilate | 6.00 mg/dL | 144 μmol/L  |
|  Cefoxitin | 660 mg/dL | 15 500 μmol/L  |
|  Cyclosporine | 0.180 mg/dL | 1.50 μmol/L  |
|  Doxycycline | 1.80 mg/dL | 40.5 μmol/L  |
|  Famvir | 0.25 mg/L | 0.778 μmol/L  |
|  Ibuprofen | 21.9 mg/dL | 1060 μmol/L  |
|  Levodopa | 0.750 mg/dL | 38.0 μmol/L  |
|  Methyldopa | 2.25 mg/dL | 107 μmol/L  |

K243575 - Page 8 of 15

{8}

|  Potentially Interfering Drug | Potential Interferent Concentration  |   |
| --- | --- | --- |
|   |  Default Units | Alternate Units  |
|  Metronidazole | 12.3 mg/dL | 719 μmol/L  |
|  N-Acetylcysteine | 15.0 mg/dL | 920 μmol/L  |
|  Phenylbutazone | 32.1 mg/dL | 1040 μmol/L  |
|  Rifampicin | 4.8 mg/dL | 58.3 μmol/L  |
|  Sodium heparin | 330 units/dL | N/A  |
|  Theophylline | 6.00 mg/dL | 333 μmol/L  |
|  Valacyclovir | 3 mg/L | 8.314 μmol/L  |

## b. Potential Cross-Reactivity

The ARCHITECT HSV-2 IgG assay was evaluated for potential cross-reactivity using specimens from individuals containing antibodies to other microorganisms or with medical conditions unrelated to HSV-2 infection. The data are summarized in the following table.

Table 6: Potential Cross-Reactivity.

|  Category | n | ARCHITECT HSV-2 IgG |   | False Positive Rate (%)  |
| --- | --- | --- | --- | --- |
|   |   |  Reactive | Nonreactive  |   |
|  Anti-dsDNA autoantibodies | 8 | 1 | 7 | 12.50  |
|  Antinuclear antibody | 12 | 0 | 12 | 0  |
|  Candida albicans | 13 | 0 | 13 | 0  |
|  Chlamydia trachomatis | 10 | 0 | 10 | 0  |
|  Cytomegalovirus (IgG) | 11 | 0 | 11 | 0  |
|  Elevated IgG | 12 | 1 | 11 | 8.33  |
|  Elevated IgM | 9 | 0 | 9 | 0  |
|  Epstein-Barr virus (IgG) | 12 | 0 | 12 | 0  |
|  Gardnerella vaginalis | 10 | 1 | 9 | 10.00  |
|  HAMA | 8 | 0 | 8 | 0  |
|  Hepatitis A virus IgG | 10 | 0 | 10 | 0  |
|  Hepatitis B virus IgG | 12 | 0 | 12 | 0  |
|  Hepatitis C virus IgG | 12 | 0 | 12 | 0  |

K243575 - Page 9 of 15

{9}

|  Category | n | ARCHITECT HSV-2 IgG |   | False Positive Rate (%)  |
| --- | --- | --- | --- | --- |
|   |   |  Reactive | Nonreactive  |   |
|  HSV-1 IgG | 6 | 0 | 6 | 0  |
|  Human herpesvirus-6 IgG | 13 | 1 | 12 | 7.69  |
|  Human herpesvirus-8 IgG | 10 | 2 | 8 | 20.00  |
|  Human immunodeficiency virus IgG | 11 | 0 | 11 | 0  |
|  Human papillomavirus IgG | 12 | 0 | 12 | 0  |
|  Influenza vaccine recipients | 10 | 0 | 10 | 0  |
|  Monoclonal hyperimmunoglobulinemia | 13 | 0 | 13 | 0  |
|  Mycoplasma pneumoniae | 5 | 0 | 5 | 0  |
|  Multiparous females | 3 | 0 | 3 | 0  |
|  Neisseria gonorrhea | 6 | 0 | 6 | 0  |
|  Parvovirus B19 IgG | 13 | 2 | 11 | 15.38  |
|  Pregnant females all trimesters | 6 | 0 | 6 | 0  |
|  Rheumatoid factor (RF) | 10 | 1 | 9 | 10.00  |
|  Rubella virus IgG | 12 | 0 | 12 | 0  |
|  Streptococcus | 9 | 0 | 9 | 0  |
|  Toxoplasma gondii | 10 | 1 | 9 | 10.00  |
|  Treponema pallidum | 12 | 0 | 12 | 0  |
|  Varicella-zoster virus IgG | 13 | 0 | 13 | 0  |

4. Assay Reportable Range:

Not applicable.

5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):

Kit real-Time Stability Studies

The data support the following storage conditions for the ARCHITECT HSV-2 IgG assay:

Table 7: ARCHITECT HSV-2 IgG storage conditions.

K243575 - Page 10 of 15

{10}

|  Stability Study | Claims  |
| --- | --- |
|  Reagent On-Board | Up to 30 days  |
|  Reagent Unopened Shelf Life | 10 months at 2-8°C  |
|  Reagent In-Use/Opened | 10 months at 2-8°C  |
|  Calibrator Unopened Shelf-Life | 12 months at 2-8°C  |
|  Calibrator In-Use/Opened | 12 months at 2-8°C  |
|  Controls Unopened Shelf Life | 12 months at 2-8°C  |
|  Controls In-Use/Opened | 12 months at 2-8°C  |

## Specimens Stability

The stability of specimens stored under different conditions was evaluated by testing a panel of natural and contrived samples (including Serum, Serum Separator Tube (SST), Dipotassium EDTA plasma, Lithium Heparin plasma and Lithium heparin separator on the ARCHITECT HSV-2 IgG assay. The data support the following specimen storage conditions: 1 month frozen (≤-20°C), 14 days refrigerated (2 to 8°C) off the clot, 7 days refrigerated (2 to 8°C) on the clot, 48 hours at room temperature (15 to 30°C) and up to 3 freeze/thaw cycles.

6. Detection Limit:

Not applicable.

7. Assay Cut-Off:

A study to establish the ARCHITECT HSV-2 IgG assay cutoff was performed using 505 serum samples (271 reactive, 228 nonreactive, and 6 equivocal for HSV-2 IgG antibodies).

Receiver-Operating Characteristic (ROC) curve analysis was performed. The optimal cut-off of 1.00 S/CO was selected and validated in the method comparison study (clinical agreement study).

8. Accuracy (Instrument):

N/A

9. Carry-Over:

The ARCHITECT HSV-2 IgG assay is not susceptible to within-assay sample carryover.

10. Class-specificity:

The Class specificity was supported for the ARCHITECT HSV-2 IgG assay demonstrating that the ARCHITECT HSV-2 IgG assay specifically detects IgG class immunoglobulin.

K243575 - Page 11 of 15

{11}

# B Comparison Studies:

# 1. Method Comparison with Predicate Device:

A multi-center clinical study was conducted to evaluate the clinical performance of the ARCHITECT HSV-2 IgG assay. Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) were determined comparing the performance of the ARCHITECT HSV-2 IgG assay to a composite comparator method comprised of 3 commercially available anti-HSV-2 IgG assays where a 2 out of 3 approach was followed to determine the final composite comparator method result.

A total of 915 specimens, which included sexually active individuals and pregnant females, were collected prospectively within the United States and tested at 3 independent external laboratories.

The PPA and NPA results are summarized in the following tables.

Table 8. Clinical performance of the ARCHITECT HSV-2 IgG in the Sexually Active Population (N=618).

|  Sexually Active Population | Composite Comparator Method  |   |   |   |
| --- | --- | --- | --- | --- |
|   |   |  Positive | Equivocal | Negative  |
|  ARCHITECT HSV-2 IgG | Reactive | 223 | 0 | 12  |
|   |  Nonreactive | 5 | 3 | 375  |
|   |  Total | 228 | 3 | 387  |
|   |   | PPA= 96.54% (223/231); 95%CI= 93.32% to 98.24% |  | NPA= 96.90% (375/387); 95% CI= 94.66% to 98.22%  |

Table 9. Clinical performance of the ARCHITECT HSV-2 IgG in the Pregnant Population (N=297).

|  Pregnant Population | Composite Comparator Method  |   |   |   |
| --- | --- | --- | --- | --- |
|   |   |  Positive | Equivocal | Negative  |
|  ARCHITECT HSV-2 IgG | Reactive | 78 | 0 | 3  |
|   |  Nonreactive | 4 | 0 | 212  |
|   |  Total | 82 | 0 | 215  |
|   |   | PPA= 95.12% (78/82); 95%CI= 88.12% to 98.09% |  | NPA= 98.60% (212/215); 95% CI= 95.98% to 99.52%  |

# 2. Tube Types Matrix Comparison:

Sixty-one (61) sets of matched reactive and nonreactive samples of different matrices (serum, serum separator tube, dipotassium EDTA plasma, lithium heparin plasma,

K243575 - Page 12 of 15

{12}

lithium heparin separator) from commercial sources were evaluated with the ARCHITECT HSV-2 IgG assay on the ARCHITECT i2000SR instrument for equivalency. The samples were analyzed by linear regression using serum as the comparator matrix.

Table 10. Regression analysis on matrix equivalence.

|  Tube (y) vs. Serum (x) | Regression Equation | Sample Interval | N^{a} | r^{b}  |
| --- | --- | --- | --- | --- |
|  Serum separator tube | y = 1.03x – 0.0350 S/CO | 0.50-54.76 S/CO | 61 | 0.998  |
|  Plasma, dipotassium EDTA | y = 1.02x + 0.0079 S/CO | 0.56-54.02 S/CO | 61 | 0.997  |
|  Plasma, lithium heparin | y = 1.03x – 0.0029 S/CO | 0.55-54.77 S/CO | 61 | 0.996  |
|  Plasma, lithium heparin separator | y = 1.00x + 0.0343 S/CO | 0.56-54.55 S/CO | 61 | 0.997  |

a Number of samples tested
b Correlation coefficient

The following tube types are acceptable for use with the ARCHITECT HSV-2 IgG assay:
- Serum
- Serum separator
- Plasma (dipotassium EDTA, Lithium heparin, Lithium heparin separator)

## C Clinical Agreement Study:

1. Clinical Sensitivity: Not applicable
2. Clinical Specificity: Not Applicable.
3. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):

## CDC Panel agreement

The CDC panel consisted of 2 aliquots each of 50 serum samples with unknown HSV-2 status for a total of 100 blind characterized samples.

The ARCHITECT HSV-2 IgG assay demonstrated 100% Positive Percent Agreement (PPA) for reactive samples (30/30) and 97.14% Negative Percent Agreement (NPA) for nonreactive samples (68/70) in concordance with the results provided by the CDC.

## Low Prevalence Specificity

An additional study was performed to determine the specificity of the ARCHITECT HSV-2 IgG assay using 139 serum specimens from 16-19 year old individuals in a nonsexually transmitted disease setting within the US. The ARCHITECT HSV-2 IgG assay

K243575 - Page 13 of 15

{13}

demonstrated a NPA of  $98.48\%$  (130/132) with a  $95\%$  two-sided confidence interval (CI) of  $94.64\%$  to  $99.58\%$  by Wilson score.

# D Clinical Cut-Off:

See Assay Cut-Off

# E Expected Values/Reference Range:

Representative performance data are provided in this section. Results obtained in individual laboratories may vary considering HSV prevalence. The prevalence may vary depending upon geographical location, age, sex, type of test employed, specimen collection and handling procedures as well as clinical history of the patient.

It is recommended that each laboratory determine its own reference range based upon its particular local and population characteristics.

Clinical performance of the ARCHITECT HSV-2 IgG assay was evaluated with samples collected prospectively from 915 individuals from the intended use population. Of the 915 individuals, there were 670 (73%) females and 245 (27%) males. The median age was 35 years (age range: 14 to 99 years). Testing of the specimens was performed at 3 clinical testing sites.

The distribution of ARCHITECT HSV-2 IgG reactive and nonreactive results by age and sex is summarized in the following table.

Table 11. Distribution of HSV-2 IgG reactive and nonreactive results by age and sex.

|  Age Range (Years) | Sex | n | ARCHITECT HSV-2 IgG Result  |   |
| --- | --- | --- | --- | --- |
|   |   |   |  Number of Reactive (%) | Number of Nonreactive (%)  |
|  14 to 20 | Female | 45 | 14 (31%) | 31 (69%)  |
|   |  Male | 6 | 1 (17%) | 5 (83%)  |
|  21 to 30 | Female | 242 | 49 (20%) | 193 (80%)  |
|   |  Male | 49 | 11 (22%) | 38 (78%)  |
|  31 to 40 | Female | 181 | 66 (36%) | 115 (64%)  |
|   |  Male | 40 | 10 (25%) | 30 (75%)  |
|  41 to 50 | Female | 72 | 39 (54%) | 33 (46%)  |
|   |  Male | 36 | 12 (33%) | 24 (67%)  |
|  51 to 60 | Female | 46 | 24 (52%) | 22 (48%)  |
|   |  Male | 43 | 16 (37%) | 27 (63%)  |
|  61 to 70 | Female | 33 | 23 (70%) | 10 (30%)  |
|   |  Male | 32 | 16 (50%) | 16 (50%)  |
|  71 to 99 | Female | 51 | 25 (49%) | 26 (51%)  |
|   |  Male | 39 | 10 (26%) | 29 (74%)  |
|  Total | Female | 670 | 240 (36%) | 430 (64%)  |
|   |  Male | 245 | 76 (31%) | 169 (69%)  |
|   |  Overall | 915 | 316 (35%) | 599 (65%)  |

K243575 - Page 14 of 15

{14}

F Other Supportive Instrument Performance Characteristics Data:
N/A

VIII Proposed Labeling:
The labeling supports the finding of substantial equivalence for this device.

IX Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

K243575 - Page 15 of 15

---

**Source:** [https://fda.innolitics.com/submissions/MI/subpart-d%E2%80%94serological-reagents/MYF/K243575](https://fda.innolitics.com/submissions/MI/subpart-d%E2%80%94serological-reagents/MYF/K243575)

**Published by [Innolitics](https://innolitics.com)** — a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices. If you're preparing [a 510(k)](https://innolitics.com/services/510ks/), [a De Novo](https://innolitics.com/services/regulatory/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/), [get in touch](https://innolitics.com/contact).

**Cite:** Innolitics at https://innolitics.com