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.

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).

AI/ML Overview

The document describes the ARCHITECT HSV-2 IgG assay, a diagnostic device for detecting specific IgG antibodies to herpes simplex virus type 2 (HSV-2). The study aims to demonstrate that this new device is substantially equivalent to legally marketed predicate devices.

While the document does not explicitly state "acceptance criteria" in the format of a separate table setting thresholds beforehand, the performance summary sections detail the studies and the observed performance. The key performance metrics demonstrated are:

Clinical Performance (Positive Percent Agreement - PPA and Negative Percent Agreement - NPA): This is the primary measure of the device's accuracy in correctly identifying positive and negative samples for HSV-2 IgG antibodies.
Precision (Within-Laboratory and Reproducibility): These studies evaluate the consistency and reliability of the assay results across different runs, days, and sites.
Analytical Specificity (Interference and Cross-reactivity): These studies assess the device's ability to accurately measure HSV-2 IgG without being affected by other substances or related conditions.
Specimen Collection Types: This confirms the assay's performance across various accepted sample types.
Carry-Over: Verifies that prior samples do not affect subsequent sample results.

Here's an interpretation of the implied acceptance criteria and reported performance based on the provided document:

Acceptance Criteria and Reported Device Performance

Performance Metric	Implicit Acceptance Criteria (Inferred from study design/general diagnostic device standards)	Reported Device Performance
Clinical Performance	High Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) compared to a composite comparator, indicating strong diagnostic accuracy.	Sexually Active Population:- PPA: 96.54% (223/231) with 95% CI: 93.32% to 98.24%- NPA: 96.90% (375/387) with 95% CI: 94.66% to 98.22%Pregnant Population:- PPA: 95.12% (78/82) with 95% CI: 88.12% to 98.09%- NPA: 98.60% (212/215) with 95% CI: 95.98% to 99.52%CDC Panel Agreement:- PPA (Reactive samples): 100% (30/30)- NPA (Nonreactive samples): 97.14% (68/70)
Precision (Within-Laboratory)	Low %CV for different panels and controls, demonstrating consistent results within the laboratory.	20-Day Within-Laboratory Precision:- Positive Control: Mean S/CO 3.01, Within-Laboratory %CV 3.9- Serum Panel 2: Mean S/CO 1.60, Within-Laboratory %CV 6.8- Serum Panel 3: Mean S/CO 2.47, Within-Laboratory %CV 11.6- Plasma Panels: %CVs ranging from 3.3 to 5.712-Day Within-Laboratory Precision (Higher Analyte Levels):- Serum Panel 4: Mean S/CO 7.14, Within-Laboratory %CV 5.2- Serum Panel 5: Mean S/CO 14.73, Within-Laboratory %CV 4.6- Plasma Panel 4: Mean S/CO 7.85, Within-Laboratory %CV 4.5- Plasma Panel 5: Mean S/CO 14.90, Within-Laboratory %CV 5.0
Precision (Reproducibility)	Low %CV across multiple sites/instruments, demonstrating consistent results regardless of testing location.	Reproducibility (3 testing sites):- Positive Control: Mean S/CO 2.98, Reproducibility %CV 5.2- Serum Panel 2: Mean S/CO 1.56, Reproducibility %CV 4.0- Serum Panel 3: Mean S/CO 2.52, Reproducibility %CV 4.3- Plasma Panels: %CVs ranging from 5.2 to 5.4
Analytical Specificity (Interference)	Minimal impact (<10% absolute difference for reactive, <0.10 S/CO for nonreactive) from potentially interfering endogenous substances and drugs.	Observed differences met the criteria: <10% absolute difference for reactive samples and <0.10 S/CO absolute difference for nonreactive samples for all listed endogenous substances and drugs.
Analytical Specificity (Cross-reactivity)	Low false positive rates (< 20%) when testing specimens with antibodies to other microorganisms or unrelated medical conditions.	False positive rates observed:- Anti-dsDNA autoantibodies: 12.50% (1/8)- Elevated IgG: 8.33% (1/12)- Gardnerella vaginalis: 10.00% (1/10)- Human herpesvirus-6 IgG: 7.69% (1/13)- Human herpesvirus-8 IgG: 20.00% (2/10)- Parvovirus B19 IgG: 15.38% (2/13)- Rheumatoid Factor (RF): 10.00% (1/10)- Toxoplasma gondii: 10.00% (1/10)No false positives observed for many other categories.
Specimen Collection Types	Equivalent performance across specified collection tube types compared to serum.	High correlation coefficients (r ≥ 0.996) and linear regression equations close to y=x for serum separator tube, dipotassium EDTA plasma, lithium heparin plasma, and lithium heparin plasma separator compared to serum.
Carry-Over	No susceptibility to within-assay sample carryover.	The ARCHITECT HSV-2 IgG assay is not susceptible to within-assay sample carryover.

Study Details:

A table of acceptance criteria and the reported device performance: See table above.
Sample size used for the test set and the data provenance:
- Clinical Agreement Study: 915 specimens total (prospectively collected). Data provenance: Collected prospectively within the United States.
  - Sexually Active Population: 618 specimens (228 positive, 3 equivocal, 387 negative by composite comparator)
  - Pregnant Population: 297 specimens (82 positive, 0 equivocal, 215 negative by composite comparator)
- CDC Panel Agreement: 100 blind characterized serum samples (50 unique samples, 2 aliquots each). Data provenance: From the Centers for Disease Control and Prevention (CDC).
- Cut-off Establishment: 505 serum samples (271 reactive, 228 nonreactive, 6 equivocal for HSV-2 IgG antibodies).
- Specimen Collection Types: 61 sets of unique serum samples paired with other tube types.
- Precision Studies: 240-244 samples per panel/control for 20-day study, 96 samples per panel for 12-day study, 90 samples per panel for reproducibility study (all tested multiple times).
- Analytical Specificity (Interference/Cross-reactivity): Varies per substance/condition, typically around 8-13 samples each.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
The document does not explicitly state the number or qualifications of experts for establishing ground truth for the clinical agreement study. Instead, for the clinical performance evaluation, a "composite comparator method of 3 commercially available anti-HSV-2 IgG assays where a 2 out of 3 approach was followed" was used as the ground truth. This indicates a consensus or analytical comparison approach rather than expert human interpretation of results.
For the CDC panel, it states "100 blind characterized samples," implying the CDC characterized these samples, likely through a robust expert-derived or reference method.
Adjudication method (e.g. 2+1, 3+1, none) for the test set:
For the main clinical agreement study, the ground truth was established by a "2 out of 3 approach" using three commercially available anti-HSV-2 IgG assays. This is a form of adjudicated ground truth.
If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
Not applicable. This device is a fully automated chemiluminescent microparticle immunoassay (CMIA) for the qualitative detection of specific IgG antibodies to HSV-2. It does not involve human readers for interpretation in the same way an AI for medical imaging (e.g., radiology) would, nor does it describe a human-in-the-loop AI assistance scenario. The output is a quantitative measure (S/CO) interpreted against a fixed cutoff.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
Yes, the entire study effectively describes the standalone performance of the ARCHITECT HSV-2 IgG assay. As an automated immunoassay, it inherently operates without human interpretation of the primary result output, beyond clerical tasks and result reporting based on predefined cutoffs.
The type of ground truth used (expert consensus, pathology, outcomes data, etc):
For the primary clinical agreement study, the ground truth was established by a "composite comparator method" derived from the results of three commercially available anti-HSV-2 IgG assays, using a "2 out of 3 approach." This is a form of analytical ground truth based on established diagnostic methods.
For the CDC panel, the ground truth was "characterized samples" provided by the CDC, implying a reference standard or validated characterization by that institution.
The sample size for the training set:
The document does not explicitly describe a separate "training set" in the context of an AI/machine learning model development. This is a traditional IVD device (immunoassay). The "Cut-off" section mentions a study using 505 serum samples to establish the assay's cutoff, which is a key parameter for defining reactive/nonreactive results. This could be considered analogous to a "training" or "calibration" set for the assay's performance characteristics.
How the ground truth for the training set was established:
As mentioned in point 8, the assay's cutoff was established using a Receiver-Operating Characteristic (ROC) curve analysis on 505 serum samples. The ground truth for these 505 samples (whether they were truly reactive or nonreactive for HSV-2 IgG antibodies) is not explicitly stated but would have been determined by a reference method or clinical diagnosis prior to cutoff establishment. The document states these samples were "271 reactive, 228 nonreactive, and 6 equivocal for HSV-2 IgG antibodies," implying this pre-classification was the ground truth for selecting the optimal cutoff.

Summary

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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 (1-800-638-2041 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)

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'sInformation	Biokit, S.A.Av. Can Montcau, 7Lliçà d'Amunt 08186Barcelona (Spain)
-------------------------------	--------------------------------------------------------------------------------

2. Contact Person	Janna Puig, Regulatory Affairs ManagerPhone: +34 93 860 90 00Email: jpuig@werfen.com
-------------------	----------------------------------------------------------------------------------------------

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

4. Device TradeName	ARCHITECT HSV-2 IgG
--------------------------	---------------------

5. RegulatoryInformation	Regulation Number	21 CFR 866.3305
	Regulation Description	Herpes simplex virusserological assays.
	Classification	Class II SpecialControls
	Product Code	MYF
	Classification Panel	Microbiology

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7. Indications forUse / IntendedUse	The ARCHITECT HSV-2 IgG assay is achemiluminescent microparticle immunoassay(CMIA) used for the qualitative detection ofspecific IgG antibodies to herpes simplex virustype 2 (HSV-2) in human serum (collected inserum and serum separator tubes) and plasma(collected in dipotassium EDTA, lithium heparin,and lithium heparin plasma separator tubes) onthe ARCHITECT i System.The ARCHITECT HSV-2 IgG assay is to be usedfor testing sexually active adults or expectantmothers to aid in the presumptive diagnosis ofHSV-2 infection. The test results may notdetermine the state of active lesions orassociated disease manifestations, particularlyfor primary infection. The predictive value of areactive or nonreactive result depends on theprevalence of HSV-2 infection in the populationand the pre-test likelihood of HSV-2 infection.NOTE: The performance of the ARCHITECT HSV-2 IgG assay has not been established for use inthe pediatric population, for neonatal screening,or for testing immunocompromised orimmunosuppressed patients. The assay has notbeen FDA cleared or approved for screening bloodor plasma donors.
---------------------------------------------	------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

7. Indications forUse / IntendedUse

The ARCHITECT HSV-2 IgG assay is achemiluminescent microparticle immunoassay(CMIA) used for the qualitative detection ofspecific IgG antibodies to herpes simplex virustype 2 (HSV-2) in human serum (collected inserum and serum separator tubes) and plasma(collected in dipotassium EDTA, lithium heparin,and lithium heparin plasma separator tubes) onthe ARCHITECT i System.The ARCHITECT HSV-2 IgG assay is to be usedfor testing sexually active adults or expectantmothers to aid in the presumptive diagnosis ofHSV-2 infection. The test results may notdetermine the state of active lesions orassociated disease manifestations, particularlyfor primary infection. The predictive value of areactive or nonreactive result depends on theprevalence of HSV-2 infection in the populationand the pre-test likelihood of HSV-2 infection.NOTE: The performance of the ARCHITECT HSV-2 IgG assay has not been established for use inthe pediatric population, for neonatal screening,or for testing immunocompromised orimmunosuppressed patients. The assay has notbeen FDA cleared or approved for screening bloodor plasma donors.

---------------------------------------------

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8. DeviceDescription	The ARCHITECT HSV-2 IgG assay is anautomated, two-step immunoassay for thequalitative detection of IgG antibodies to HSV-2in human serum and plasma usingchemiluminescent microparticle immunoassay(CMIA) technology.
	The kit contains different components: Reagent(microparticles, conjugate and assay diluent),Calibrator, and external Controls (reactive andnonreactive).

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COMPARISON PREDICATE
Item	Predicate	New Device
Trade Names	HSV-1 & HSV-2Differentiation ImmunoblotIgG	ARCHITECT HSV-2 IgG,ARCHITECT HSV-2 IgGCalibrator, ARCHITECT HSV-2 IgG Controls
510K no.	K000238	K243575
Manufacturer	MRL DiagnosticsCypress, CA 90630 -USA	Abbott Ireland DiagnosticsDivisionFinisklin Business Park,Sligo, Ireland
Similarities
Intended use	MRL Diagnostics' HSV-1 &HSV-2 DifferentiationImmunoblot IgG test isintended for qualitativelydetecting the presence orabsence of human IgG classantibodies to HSV-1 andHSV-2 in human sera.The test is indicated fortesting sexually activeadults or expectant mothersfor aiding in thepresumptive diagnosis ofHSV-1 and HSV-2 infection.The predictive value of apositive or negative resultdepends on the population'sprevalence and pretestlikelihood of HSV-1 andHSV-2 infection. Theperformance of this assayhas not been established foruse in a pediatricpopulation, for neonatalscreening, for testing ofimmunocompromisedpatients, for use by a point	The ARCHITECT HSV-2 IgGassay is a chemiluminescentmicroparticle immunoassay(CMIA) used for thequalitative detection ofspecific IgG antibodies toherpes simplex virus type 2(HSV- 2) in human serum(collected in serum andserum separator tubes) andplasma (collected indipotassium EDTA, lithiumheparin, and lithium heparinplasma separator tubes) onthe ARCHITECT i System.The ARCHITECT HSV-2 IgGassay is to be used fortesting sexually active adultsor expectant mothers to aidin the presumptive diagnosisof HSV-2 infection. The testresults may not determinethe state of active lesions orassociated diseasemanifestations, particularlyfor primary infection. Thepredictive value of a reactiveor nonreactive result

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	of care facility or for usewith automated equipment.	depends on the prevalenceof HSV-2 infection in thepopulation and the pre-testlikelihood of HSV-2 infection.NOTE: The performance ofthe ARCHITECT HSV-2 IgGassay has not beenestablished for use in thepediatric population, forneonatal screening, or fortesting immunocompromisedor immunosuppressedpatients. The assay has notbeen FDA cleared orapproved for screeningblood or plasma donors.
Measurand	Human IgG class antibodiesto HSV-1 and HSV-2	Human IgG antibodies toHSV-2
RegulationSection	21 CFR 866.3305	Same
Classification	Class II Special Controls	Same
Assay Type	Qualitative	Same
Differences
Product Code	LGC	MYF
Technology	Nitrocellulose immunoblot	Chemiluminescentimmunoassay
Sample type	Human serum	Human serum (collected inserum and serum separatortubes) and plasma (collectedin dipotassium EDTA, lithiumheparin, and lithium heparinplasma separator tubes)
ResultInterpretation	Visually evaluate multiplebands	The cutoff is 1.00 S/CO.<1.00 S/CO =Nonreactive≥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(x)	Regression Equation	SampleInterval	Na	rb
Serum separator tube	y = 1.03x - 0.0350S/CO	0.50-54.76S/CO	61	0.998
Plasma, dipotassiumEDTA	y = 1.02x + 0.0079S/CO	0.56-54.02S/CO	61	0.997
Plasma, lithium heparin	y = 1.03x - 0.0029S/CO	0.55-54.77S/CO	61	0.996
Plasma, lithium heparinseparator	y = 1.00x + 0.0343S/CO	0.56-54.55S/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(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

	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(Repeatability)		Between-Lot		Within-Laboratory
Sample	n	Mean(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(S/CO)	RepeatabilitySD	Repeatability%CV	Between-RunSD	Between-Run%CV	Between-DaySD	Between-Day%CV	Between-Site/InstrumentSD	Between-Site/Instrument%CV	ReproducibilityªSD	Reproducibilityª%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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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.

AgeRange(Years)	Sex	n	ARCHITECT HSV-2 IgGResult
			Number ofReactive (%)	Number ofNonreactive(%)
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
ARCHITECTHSV-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 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
ARCHITECTHSV-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%

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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.

Regulation Number and Section

§ 866.3305 Herpes simplex virus serological assays.

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