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

K243575 · Biokit, S.A. · MYF · Feb 12, 2025 · Microbiology

Device Facts

• Record ID: K243575
• Device Name: ARCHITECT HSV-2 IgG, ARCHITECT HSV-2 IgG Calibrator, ARCHITECT HSV-2 IgG Controls
• Applicant: Biokit, S.A.
• Product Code: MYF · Microbiology
• Decision Date: Feb 12, 2025
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3305
• Device Class: Class 2

Intended 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.

Indications for Use

Indicated for sexually active adults or expectant mothers to aid in the presumptive diagnosis of HSV-2 infection. Not for pediatric use, neonatal screening, or immunocompromised/immunosuppressed patients. Not for blood or plasma donor screening.

Regulatory Classification

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)

Submission Summary (Full Text)

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Build Correspondence

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Date: February 12, 2025

Biokit, S.A. Janna Puig Regulatory Affairs Manager Av. Can Montcau 7 Lliçà d'Amunt, Barcelona, 08186 Spain

Re: K243575

Trade/Device Name: ARCHITECT HSV-2 IgG, ARCHITECT HSV-2 IgG Calibrator, ARCHITECT HSV-2 IgG Controls Regulation Number: 21 CFR 866.3305 Regulation Name: Herpes Simplex Virus Serological Assays Regulatory Class: Class II Product Code: MYF Dated: November 19, 2024 Received: November 19, 2024

Dear Janna Puig:

We have reviewed your section 510(k) premarket notification of intent to market the device referenced above and 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 (the Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database available at https://www.accessdata.fda.gov/scripts/cdrb/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device"

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(https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30. Design controls; 21 CFR 820.90. Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review. the OS regulation reguires device manufacturers to review and approve changes to device design and production (21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rule"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-devices/device-advicecomprehensive-regulatory-assistance/unique-device-identification-system-udi-system.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE(@fda.hhs.gov) or phone [phone] or 301-796-7100).

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Sincerely,

Image /page/2/Picture/3 description: The image contains two lines of text. The first line reads "JORGE L." and the second line reads "MUNOZ-S". The text is in a simple, sans-serif font and is displayed in black against a white background. The text appears to be a name.

Digitally signed by JORGE L. MUNOZ -S Date: 2025.02.12 15:35:57 -04'00'

Jorge Munoz, Ph.D. Deputy Branch Chief Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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### Indications for Use

510(k) Number (if known) K243575

Device Name ARCHITECT HSV-2 IgG

#### Indications for Use (Describe)

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 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 lessociated 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 immunosompromised or immunosuppressed patients. The assay has not been FDA cleared or approved for screening blood or plasma donors.

| Type of Use (Select one or both, as applicable) | | | | | |
|-----------------------------------------------------------------------------------|--------------------------------------------------|-----------------------------------------------|--|--|--|
| | X Prescription Use (Part 21 CFR 801 Subpart D) | ] Over-The-Counter Use (21 CFR 801 Subpart C) | | | |
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### 510(k) SUMMARY

This 510(k) Summary of Safety and Effectiveness is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and 21 CFR 807.92.

| 1. Submitter's<br>Information | Biokit, S.A.<br>Av. Can Montcau, 7<br>Lliçà d'Amunt 08186<br>Barcelona (Spain) |
|-------------------------------|--------------------------------------------------------------------------------|
|-------------------------------|--------------------------------------------------------------------------------|

| 2. Contact Person | Janna Puig, Regulatory Affairs Manager<br>Phone: [phone]<br>Email: [e-mail] |
|-------------------|----------------------------------------------------------------------------------------------|
|-------------------|----------------------------------------------------------------------------------------------|

| 3. Preparation Date | 2025-02-12 |
|---------------------|------------|
|---------------------|------------|

| 4. Device Trade<br>Name | ARCHITECT HSV-2 IgG |
|--------------------------|---------------------|
|--------------------------|---------------------|

| 5. Regulatory<br>Information | Regulation Number | 21 CFR 866.3305 |
|------------------------------|------------------------|---------------------------------------------|
| | Regulation Description | Herpes simplex virus<br>serological assays. |
| | Classification | Class II Special<br>Controls |
| | Product Code | MYF |
| | Classification Panel | Microbiology |

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| 7. Indications for<br>Use / Intended<br>Use | The ARCHITECT HSV-2 IgG assay is a<br>chemiluminescent microparticle immunoassay<br>(CMIA) used for the qualitative detection of<br>specific IgG antibodies to herpes simplex virus<br>type 2 (HSV-2) in human serum (collected in<br>serum and serum separator tubes) and plasma<br>(collected in dipotassium EDTA, lithium heparin,<br>and lithium heparin plasma separator tubes) on<br>the ARCHITECT i System.<br>The ARCHITECT HSV-2 IgG assay is to be used<br>for testing sexually active adults or expectant<br>mothers to aid in the presumptive diagnosis of<br>HSV-2 infection. The test results may not<br>determine the state of active lesions or<br>associated disease manifestations, particularly<br>for primary infection. The predictive value of a<br>reactive or nonreactive result depends on the<br>prevalence of HSV-2 infection in the population<br>and the pre-test likelihood of HSV-2 infection.<br>NOTE: The performance of the ARCHITECT HSV-<br>2 IgG assay has not been established for use in<br>the pediatric population, for neonatal screening,<br>or for testing immunocompromised or<br>immunosuppressed patients. The assay has not<br>been FDA cleared or approved for screening blood<br>or plasma donors. |
|---------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
|---------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|

| 8. Device<br>Description | The ARCHITECT HSV-2 IgG assay is an<br>automated, two-step immunoassay for the<br>qualitative detection of IgG antibodies to HSV-2<br>in human serum and plasma using<br>chemiluminescent microparticle immunoassay<br>(CMIA) technology. |
|--------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | The kit contains different components: Reagent<br>(microparticles, conjugate and assay diluent),<br>Calibrator, and external Controls (reactive and<br>nonreactive). |

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T

| COMPARISON PREDICATE | | |
|----------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Item | Predicate | New Device |
| Trade Names | HSV-1 & HSV-2<br>Differentiation Immunoblot<br>IgG | ARCHITECT HSV-2 IgG,<br>ARCHITECT HSV-2 IgG<br>Calibrator, ARCHITECT HSV-<br>2 IgG Controls |
| 510K no. | K000238 | K243575 |
| Manufacturer | MRL Diagnostics<br>Cypress, CA 90630 -USA | Abbott Ireland Diagnostics<br>Division<br>Finisklin Business Park,<br>Sligo, Ireland |
| Similarities | | |
| Intended use | MRL Diagnostics' HSV-1 &<br>HSV-2 Differentiation<br>Immunoblot IgG test is<br>intended for qualitatively<br>detecting the presence or<br>absence of human IgG class<br>antibodies to HSV-1 and<br>HSV-2 in human sera.<br>The test is indicated for<br>testing sexually active<br>adults or expectant mothers<br>for aiding in the<br>presumptive diagnosis of<br>HSV-1 and HSV-2 infection.<br>The predictive value of a<br>positive or negative result<br>depends on the population's<br>prevalence and pretest<br>likelihood of HSV-1 and<br>HSV-2 infection. The<br>performance of this assay<br>has not been established for<br>use in a pediatric<br>population, for neonatal<br>screening, for testing of<br>immunocompromised<br>patients, for use by a point | The ARCHITECT HSV-2 IgG<br>assay is a chemiluminescent<br>microparticle immunoassay<br>(CMIA) used for the<br>qualitative detection of<br>specific IgG antibodies to<br>herpes simplex virus type 2<br>(HSV- 2) in human serum<br>(collected in serum and<br>serum separator tubes) and<br>plasma (collected in<br>dipotassium EDTA, lithium<br>heparin, and lithium heparin<br>plasma separator tubes) on<br>the ARCHITECT i System.<br>The ARCHITECT HSV-2 IgG<br>assay is to be used for<br>testing sexually active adults<br>or expectant mothers to aid<br>in the presumptive diagnosis<br>of HSV-2 infection. The test<br>results may not determine<br>the state of active lesions or<br>associated disease<br>manifestations, particularly<br>for primary infection. The<br>predictive value of a reactive<br>or nonreactive result |

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| | of care facility or for use<br>with automated equipment. | depends on the prevalence<br>of HSV-2 infection in the<br>population and the pre-test<br>likelihood of HSV-2 infection.<br>NOTE: The performance of<br>the ARCHITECT HSV-2 IgG<br>assay has not been<br>established for use in the<br>pediatric population, for<br>neonatal screening, or for<br>testing immunocompromised<br>or immunosuppressed<br>patients. The assay has not<br>been FDA cleared or<br>approved for screening<br>blood or plasma donors. | | |
|--------------------------|----------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--|--|
| Measurand | Human IgG class antibodies<br>to HSV-1 and HSV-2 | Human IgG antibodies to<br>HSV-2 | | |
| Regulation<br>Section | 21 CFR 866.3305 | Same | | |
| Classification | Class II Special Controls | Same | | |
| Assay Type | Qualitative | Same | | |
| Differences | | | | |
| Product Code | LGC | MYF | | |
| Technology | Nitrocellulose immunoblot | Chemiluminescent<br>immunoassay | | |
| Sample type | Human serum | Human serum (collected in<br>serum and serum separator<br>tubes) and plasma (collected<br>in dipotassium EDTA, lithium<br>heparin, and lithium heparin<br>plasma separator tubes) | | |
| Result<br>Interpretation | Visually evaluate multiple<br>bands | The cutoff is 1.00 S/CO.<br><1.00 S/CO =Nonreactive<br>≥1.00 S/CO = Reactive | | |

## 9. Performance Summary

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#### 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.

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

#### Specimen Collection Types

Sixty-one (61) sets of unique serum samples paired with samples collected in serum separator tube (SST), dipotassium EDTA plasma, lithium-heparin plasma and lithium heparin plasma separator tube (PST) were evaluated with the ARCHITECT HSV-2 IgG assay on the ARCHITECT i2000SR instrument to support equivalent performance using each of these specimen types. The samples were analyzed by linear regression using serum as comparator matrix as shown in the table below:

| Tube (y) vs. Serum<br>(x) | Regression Equation | Sample<br>Interval | Na | rb |
|--------------------------------------|----------------------------|--------------------|----|-------|
| Serum separator tube | y = 1.03x - 0.0350<br>S/CO | 0.50-54.76<br>S/CO | 61 | 0.998 |
| Plasma, dipotassium<br>EDTA | y = 1.02x + 0.0079<br>S/CO | 0.56-54.02<br>S/CO | 61 | 0.997 |
| Plasma, lithium heparin | y = 1.03x - 0.0029<br>S/CO | 0.55-54.77<br>S/CO | 61 | 0.996 |
| Plasma, lithium heparin<br>separator | y = 1.00x + 0.0343<br>S/CO | 0.56-54.55<br>S/CO | 61 | 0.997 |

ªNumber of samples tested

bCorrelation 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). ●

#### Precision

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

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

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# wer

ARCHITECT HSV-2 IgG Controls, and 1 ARCHITECT i2000SR instrument. The 20-Day within laboratory precision data is shown in the following table.

| Sample | n | Mean<br>(S/CO) | Within-Run<br>(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 |

| | Table 1. 20-Day Within-Laboratory Precision | | |
|--|---------------------------------------------|--|--|
|--|---------------------------------------------|--|--|

N/A = Not applicable

ª Calibrator and reagent lots are confounded.

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

CSerum Panel 3 was tested for one additional day.

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

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 | | |
|--|---------------------------------------------|--|--|
|--|---------------------------------------------|--|--|

| | | Within-Run<br>(Repeatability) | | Between-Lot | | Within-Laboratory | | |
|----------------|----|-------------------------------|-------|-------------|-------|-------------------|-------|-----|
| Sample | n | Mean<br>(S/CO) | 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 |

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| Plasma Panel 5 | 96 | 14.90 | 0.578 | 3.9 | 0.000 | 0.0 | 0.745 | 5.0 |
|----------------|----|-------|-------|-----|-------|-----|-------|-----|

ªIncludes within-run, between-run, between-day, and between-lot variability.

### 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.

| Sample | n | Mean<br>(S/CO) | Repeatability<br>SD | Repeatability<br>%CV | Between-Run<br>SD | Between-Run<br>%CV | Between-Day<br>SD | Between-Day<br>%CV | Between-Site/Instrument<br>SD | Between-Site/Instrument<br>%CV | Reproducibilityª<br>SD | Reproducibilityª<br>%CV |
|------------------|----|----------------|---------------------|----------------------|-------------------|--------------------|-------------------|--------------------|-------------------------------|--------------------------------|------------------------|-------------------------|
| Negative Control | 90 | 0.29 | 0.01 | N/A | 0.00 | N/A | 0.00 | 0.9 | 0.01 | 4.8 | 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 | 1.4 | 0.02 | 2.4 | 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 | 1.7 | 0.03 | 3.5 | 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 |

#### Table 3. Reproducibility

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

### Analytical Specificity

#### Interference

### Potentially Interfering Endoqenous 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.

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.

| Potentially Interfering | Potential Interferent Concentration | | | | |
|--------------------------|-------------------------------------|-----------------|--|--|--|
| Endogenous Substance | Default Units | Alternate Units | | | |
| Bilirubin (Conjugated) | 40 mg/dL | 475 µmol/L | | | |
| Bilirubin (Unconjugated) | 40 mg/dL | 684 umol/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 q/L | | | |
| Total Cholesterol | 400 mg/dL | 10.3 mmol/L | | | |

#### Table 4. Potentially Interfering Endogenous Substances

#### Table 5. Potentially Interfering Drugs

| | Potential Interferent Concentration | |
|------------------------------|-------------------------------------|-----------------|
| Potentially Interfering Drug | 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 |

Traditional 510(k): ARCHITECT HSV-2 IgG

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| | Potential Interferent Concentration | |
|--------------------|-------------------------------------|---------------|
| 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 |
| 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 |

### 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. When testing with the ARCHITECT HSV-2 IgG assay:

- । Out of 8 specimens with Anti-dsDNA autoantibodies, 1 resulted in false reactive result.
- -Out of 12 specimens with elevated IgG, 1 resulted in false reactive result.
- Out of 10 Gardnerella vaginalis specimens, 1 resulted in false reactive । result.
- । Out of 13 Human herpesvirus-6 IgG specimens, 1 resulted in false reactive result.
- । Out of 10 Human herpesvirus-8 IgG specimens, 2 resulted in false reactive result.

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- Out of 13 Parvovirus B19 IgG, 2 resulted in false reactive results. ।
- -Out of 10 RF specimens, 1 resulted in false reactive result.
- -Out of 10 Toxoplasma gondii specimens, 1 resulted in false reactive result.

The data are summarized in the following table.

| Category | n | ARCHITECT HSV-2 IgG Reactive | ARCHITECT HSV-2 IgG Nonreactive | False Positive Rate (%) |
|-------------------------------------------------|----|------------------------------|---------------------------------|-------------------------|
| Anti-dsDNA autoantibodies | 8 | 1 | 7 | 12.50 |
| Antinuclear antibody (ANA) | 12 | 0 | 12 | 0 |
| Candida albicans | 13 | 0 | 13 | 0 |
| Chlamydia trachomatis | 10 | 0 | 10 | 0 |
| Cytomegalovirus (CMV) IgG | 11 | 0 | 11 | 0 |
| Elevated IgG | 12 | 1 | 11 | 8.33 |
| Elevated IgM | 9 | 0 | 9 | 0 |
| Epstein-Barr virus (EBV) IgG | 12 | 0 | 12 | 0 |
| Gardnerella vaginalis | 10 | 1 | 9 | 10.00 |
| HAMA | 8 | 0 | 8 | 0 |
| Hepatitis A virus (HAV) IgG | 10 | 0 | 10 | 0 |
| Hepatitis B virus (HBV) IgG | 12 | 0 | 12 | 0 |
| Hepatitis C virus (HCV) IgG | 12 | 0 | 12 | 0 |
| 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 (HIV) IgG | 11 | 0 | 11 | 0 |
| Human papillomavirus (HPV) IgG | 12 | 0 | 12 | 0 |
| Monoclonal hyperimmunoglobulinemia | 13 | 0 | 13 | 0 |
| Multiparous females (≥ 2 full-term pregnancies) | 3 | 0 | 3 | 0 |
| Mycoplasma pneumoniae | 5 | 0 | 5 | 0 |
| Category | n | ARCHITECT HSV-2 IgG | | False Positive Rate (%) |
| | | Reactive | Nonreactive | |
| 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 (VZV) IgG | 13 | 0 | 13 | 0 |

#### Table 6. Potential Cross-Reactivity

510(k) Summary

Traditional 510(k): ARCHITECT HSV-2 IgG

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### CDC Panel Agreement

The CDC Performance Panel was obtained from the Centers for Disease Control and Prevention (CDC) and tested using the ARCHITECT HSV-2 IgG assay. 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 results were submitted to the CDC for data evaluation and do not imply endorsement of the assay by the CDC.

The ARCHITECT HSV-2 IgG assay demonstrated 100% Positive Percent Agreement (PPA) for reactive samples (30/30) and 97.14% Neqative Percent Agreement (NPA) for nonreactive samples (68/70) when evaluating the CDC performance panel.

### 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).

A 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.

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# wert

#### Carry-Over

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

#### Expected Values

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 915 samples collected prospectively from 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.

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

#### Table 7. Distribution of HSV-2 IgG reactive and nonreactive results by age and sex.

Traditional 510(k): ARCHITECT HSV-2 IgG

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| | Female | 670 | 240 (36%) | 430 (64%) |
|-------|---------|-----|-----------|-----------|
| Total | Male | 245 | 76 (31%) | 169 (69%) |
| | Overall | 915 | 316 (35%) | 599 (65%) |

### Clinical Agreement Study

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 by comparing the performance of the ARCHITECT HSV-2 IgG assay to a composite comparator method 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.

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

Table 8. Clinical Performance of the ARCHITECT HSV-2 IgG Assay in the Sexually Active Population

Table 9. Clinical Performance of the ARCHITECT HSV-2 IgG Assay in the Pregnant Population.

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

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# W

#### 10. Stability

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

| 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 |

#### Table 10. ARCHITECT HSV-2 IgG storage conditions

#### 11. Conclusion

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