ADVIA Centaur Herpes-2 IgG
Device Facts
| Record ID | K181334 |
|---|---|
| Device Name | ADVIA Centaur Herpes-2 IgG |
| Applicant | Biokit, S.A. |
| Product Code | MYF · Microbiology |
| Decision Date | Aug 23, 2018 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 866.3305 |
| Device Class | Class 2 |
Indications for Use
The ADVIA Centaur® Herpes-2 IgG (HSV2) assay is for in vitro diagnostic use in the qualitative determination of IgG antibodies to herpes simplex virus type 2 (HSV-2) in human serum and plasma (EDTA and lithium heparin) using the ADVIA Centaur systems. The test is indicated for testing sexually active adults or expectant mothers for aiding in the presumptive diagnosis of HSV infection. The predictive value of a positive or negative result depends on the prevalence of HSV-2 infection in the population and the pre-test likelihood of HSV-2 infection. The test is not FDA cleared for screening blood or plasma donors. The performance of this assay has not been established for immunocompromised patients, pediatric patients or matrices other than human serum and plasma (EDTA and lithium heparin).
Device Story
ADVIA Centaur Herpes-2 IgG is a fully automated two-step sandwich immunoassay using indirect chemiluminometric technology. Input: human serum or plasma (EDTA/lithium heparin). Process: specimen incubated with solid phase containing HSV-2-specific recombinant-gG2 antigen; if anti-HSV-2 IgG is present, antigen-antibody complexes form. Lite Reagent containing monoclonal anti-human IgG labeled with acridinium ester is added for detection. Used in clinical laboratories on ADVIA Centaur systems; operated by laboratory technicians. Output: qualitative index value indicating presence or absence of HSV-2 IgG antibodies. Healthcare providers use results to aid in presumptive diagnosis of HSV-2 infection. Benefits: provides automated, standardized serological testing for HSV-2 compared to manual immunoblot methods.
Clinical Evidence
Multicenter clinical study of 864 specimens (≥18 years, including 274 pregnant women). Compared to anti-HSV-2 IgG immunoblot and Western Blot confirmatory test. Overall sensitivity 95.3% (95% CI: 92.0%-97.3%), specificity 98.5% (95% CI: 97.2%-99.2%). Pregnant population sensitivity 100.0% (95% CI: 89.9%-100.0%), specificity 98.3% (95% CI: 95.8%-99.4%).
Technological Characteristics
Fully automated two-step sandwich chemiluminometric immunoassay. Solid phase: HSV-2-specific recombinant-gG2 antigen. Detection: monoclonal anti-human IgG labeled with acridinium ester. Compatible with ADVIA Centaur systems. Sample matrices: serum, EDTA plasma, lithium heparin plasma.
Indications for Use
Indicated for sexually active adults or expectant mothers to aid in the presumptive diagnosis of HSV-2 infection. Not for blood/plasma donor screening. Performance not established for immunocompromised or pediatric patients.
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
- Focus HerpeSelect 1 and 2 Immunoblot IgG (K000238)
Submission Summary (Full Text)
{0}------------------------------------------------
Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
August 23, 2018
Biokit, S.A. Joan Guixe QA & RA Director Can Male. S/N Llica d'Amunt, 08186 Barcelona, Spain
Re: K181334
Trade/Device Name: ADVIA Centaur Herpes-2 IgG Regulation Number: 21 CFR 866.3305 Regulation Name: Herpes simplex virus serological assays Regulatory Class: Class II Product Code: MYF Dated: May 17, 2018 Received: May 25, 2018
Dear Joan Guixe:
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 (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 located at https://www.accessdata.fda.gov/scripts/cdrh/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.
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
{1}------------------------------------------------
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 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; 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 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely.
# Steven R. Gitterman -S for
Uwe Scherf, Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
{2}------------------------------------------------
# Indications for Use
510(k) Number (if known) k183334
Device Name ADVIA Centaur Herpes-2 IgG
#### Indications for Use (Describe)
The ADVIA Centaur® Herpes-2 IgG (HSV2) assay is for in vitro diagnostic use in the qualitative determination of IgG antibodies to herpes simplex virus type 2 (HSV-2) in human serum and plasma (EDTA and lithium heparin) using the ADVIA Centaur systems. The test is indicated for testing sexually active adults or expectant mothers for aiding in the presumptive diagnosis of HSV infection. The predictive or negative result depends on the prevalence of HSV-2 infection in the population and the pre-test likelihood of HSV-2 infection.
The test is not FDA cleared for screening blood or plasma donors. The performance of this assay has not been established for immunocompromised patients, pediatic patients or matrices other than human serum and plasma (EDTA and lithium heparin).
| Type of Use (Select one or both, as applicable) | |
|----------------------------------------------------------------------------------|--------------------------------------------------------------------------------|
| <div> <span> Prescription Use (Part 21 CFR 801 Subpart D) </span> </div> | <div> <span> Over-The-Counter Use (21 CFR 801 Subpart C) </span> </div> |
#### CONTINUE ON A SEPARATE PAGE IF NEEDED.
This section applies only to requirements of the Paperwork Reduction Act of 1995.
### *DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.*
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
> Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
{3}------------------------------------------------
Image /page/3/Picture/0 description: The image shows the logo for Biokit, a Werfen Company. The logo consists of a stylized blue symbol resembling two overlapping letter 'V' shapes. To the right of the symbol is the word "Biokit" in gray, and below that is the text "A Werfen Company" in a smaller font size.
# 510(K) SUMMARY
This 510(k) Summary is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and 21 CFR 807.92.
| 1. Submitter's Information | Biokit, S.A.<br>Can Malé S/N<br>Lliçà d'Amunt 08186<br>Barcelona (Spain) |
|----------------------------|--------------------------------------------------------------------------|
|----------------------------|--------------------------------------------------------------------------|
| 2. Contact Person | Joan Guixer, QA & RA Director |
|-------------------|--------------------------------------------|
| | Phone: +34 93 860 90 00 / +34 657 88 33 47 |
| | Email: jguixer@biokit.com |
| 3. Preparation Date | May 17th, 2018 |
|---------------------|----------------|
|---------------------|----------------|
| 4. Device Trade Name | ADVIA Centaur Herpes-2 IgG |
|----------------------|----------------------------|
|----------------------|----------------------------|
| 5. Regulatory Information | Regulation Number | 21 CFR 866.3305 |
|---------------------------|------------------------|--------------------------------------------|
| | Regulation Description | Herpes simplex virus<br>serological assays |
| | Classification | Class II Special Controls |
| | Product Code | MYF |
| | Classification Panel | Microbiology |
| 6. Predicate Device | K000238 (Focus HerpeSelect 1 and 2 Immunoblot IgG) |
|---------------------|----------------------------------------------------|
|---------------------|----------------------------------------------------|
{4}------------------------------------------------
Image /page/4/Picture/0 description: The image shows the logo for Biokit, a Werfen Company. The logo consists of a blue abstract shape resembling two overlapping triangles on the left. To the right of the shape is the word "Biokit" in a gray, sans-serif font. Below the word "Biokit" is the text "A Werfen Company" in a smaller, gray, sans-serif font.
| 7. Indications for Use /<br>Intended Use | The ADVIA Centaur® Herpes-2 IgG (HSV2) assay is for in<br>vitro diagnostic use in the qualitative determination of<br>IgG antibodies to herpes simplex virus type 2 (HSV-2) in<br>human serum and plasma (EDTA and lithium heparin)<br>using the ADVIA Centaur systems. The test is indicated<br>for testing sexually active adults or expectant mothers<br>for aiding in the presumptive diagnosis of HSV<br>infection. The predictive value of a positive or negative<br>result depends on the prevalence of HSV-2 infection in<br>the population and the pre-test likelihood of HSV-2<br>infection. |
|------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | The test is not FDA cleared for screening blood or<br>plasma donors. The performance of this assay has not<br>been established for immunocompromised patients,<br>pediatric patients or matrices other than human serum<br>and plasma (EDTA and lithium heparin). |
| 8. Device Description | The ADVIA Centaur Herpes-2 IgG (HSV2) assay is a fully<br>automated two-step sandwich immunoassay using<br>indirect chemiluminometric technology. The specimen<br>is incubated with the Solid Phase, which contains HSV-<br>2-specific recombinant-gG2 antigen. Antigen-antibody<br>complexes will form if anti-HSV-2 antibody is present in<br>the specimen. The Lite Reagent contains monoclonal<br>anti-human IgG labeled with acridinium ester, and is<br>used to detect HSV-2 IgG in the specimen. |
|-----------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
|-----------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| COMPARISON PREDICATE | | | Manufacturer | Focus Diagnostics<br>Cypress, CA 90630 -USA | Siemens Heathcare<br>Diagnostics Inc.<br>511 Benedict Avenue,<br>Tarrytown, NY 10591- USA |
|----------------------|---------------------------------------------|----------------------------|--------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Item | Predicate | New Device | Similarities | | |
| Trade Names | Focus HerpeSelect 1 and 2<br>Immunoblot IgG | ADVIA Centaur Herpes-2 IgG | Intended use | Focus Diagnostics HerpeSelect 1<br>and 2 Immunoblot IgG test is<br>intended for qualitatively detecting<br>the presence or absence of human<br>IgG class antibodies to HSV-1 and<br>HSV-2 in human sera. The test is<br>indicated for testing sexually active<br>adults or expectant mothers for<br>aiding in the presumptive diagnosis<br>of HSV-1 and HSV-2 infection. The<br>predictive value of a positive or<br>negative result depends on the<br>population's prevalence and the<br>pretest likelihood of HSV- 1 and<br>HSV-2 infection. The performance<br>of this assay has not been<br>established for use in a pediatric<br>population, for neonatal screening,<br>for testing of<br>immunocompromised patients, for<br>use by a point of care facility or for<br>use with automated equipment | The ADVIA Centaur® Herpes-<br>2 IgG (HSV2) assay is for in<br>vitro diagnostic use in the<br>qualitative determination of<br>lgG antibodies to herpes<br>simplex virus type 2 (HSV-2)<br>in human serum and plasma<br>(EDTA and lithium heparin)<br>using the ADVIA Centaur<br>systems. The test is indicated<br>for testing sexually active<br>adults or expectant mothers<br>for aiding in the presumptive<br>diagnosis of HSV infection.<br>The predictive value of a<br>positive or negative result<br>depends on the prevalence of<br>HSV-2 infection in the<br>population and the pre-test<br>likelihood of HSV-2 infection.<br>The test is not FDA cleared<br>for screening blood or plasma<br>donors. The performance of<br>this assay has not been<br>established for<br>immunocompromised<br>patients, pediatric patients or<br>matrices other than human<br>serum and plasma (EDTA and<br>lithium heparin). |
| 510K nº | K000238 | K183334 | Measurand | To detect the presence or absence<br>of human IgG class antibodies to<br>HSV-1 and HSV-2 | To detect IgG antibodies to<br>herpes simplex virus type 2<br>(HSV-2). |
| Regulation Section | 21 CFR 866.3305 | Same | | | |
{5}------------------------------------------------
Image /page/5/Picture/0 description: The image shows the logo for Biokit, a Werfen company. The logo consists of a stylized blue "W" shape on the left, followed by the word "Biokit" in gray. Below "Biokit" is the text "A Werfen Company" in a smaller font size, also in gray. The logo is simple and modern, with a focus on the company name and affiliation.
{6}------------------------------------------------
Image /page/6/Picture/0 description: The image shows the logo for Biokit. The logo consists of a blue icon on the left and the word "Biokit" in gray on the right. Below the word "Biokit" is the phrase "A Werfen Company" in a smaller font.
| Product Code | LGC | MYF |
|----------------|---------------------------|---------------------------------------------------------|
| Classification | Class II Special Controls | Same |
| Assay Type | Qualitative | Same |
| Differences | | |
| Technology | Nitrocellulose immunoblot | Chemiluminescent<br>immunoassay |
| Sample type | Human serum | Human serum and<br>plasma (EDTA and lithium<br>heparin) |
#### 9. Performance Summary
# Precision
A precision study was performed according to CLSI EP05-A3 , using the Negative and Positive Controls as well as 6 samples prepared at different levels in the assay range. Each material was tested in duplicate, twice a day for 20 days, for a total of 80 replicates per level.
The ADVIA Centaur HSV2 assay is designed to have the following repeatability and withinlab precision requirements:
| | Design Requirement | |
|----------------------------------|-----------------------|--------------------|
| ADVIA Centaur HSV2 Level (Index) | Repeatability<br>% CV | Within-Lab<br>% CV |
| < 0.5 | NAa | NA |
| 0.51-0.79 | ≤ 10.0% | ≤ 15.0% |
| 0.80–1.20 | ≤ 6.0% | ≤ 8.0% |
| 1.21-3.00 | ≤ 5.0% | ≤ 8.0% |
| 3.01-6.00 | ≤ 5.0% | ≤ 7.0% |
| > 6.00 | ≤ 5.0% | ≤ 7.0% |
೩ NA = not applicable
The results for this study are presented below.
{7}------------------------------------------------
Image /page/7/Picture/0 description: The image shows the logo for Biokit, a Werfen Company. The logo consists of a blue abstract graphic to the left of the word "Biokit" in gray. Below the word "Biokit" is the text "A Werfen Company" in a smaller, gray font.
| Specimen Type | N | Mean<br>(Index) | Repeatability | | Within-Lab | |
|------------------------------|----|-----------------|---------------|-----------|------------|-----------|
| | | | SD | CV<br>(%) | SD | CV<br>(%) |
| Negative Control<br>(Plasma) | 80 | 0.29 | 0.01 | NAa | 0.02 | NAa |
| Positive Control<br>(Plasma) | 80 | 3.09 | 0.07 | 2.3 | 0.20 | 6.5 |
| Serum 1 | 80 | 0.36 | 0.01 | NAa | 0.02 | NAa |
| Plasma 2 | 80 | 0.63 | 0.02 | 2.4 | 0.04 | 5.9 |
| Serum 3 | 80 | 1.08 | 0.05 | 4.3 | 0.08 | 7.2 |
| Serum 4 | 80 | 2.58 | 0.09 | 3.6 | 0.20 | 7.6 |
| Serum 5 | 80 | 5.29 | 0.09 | 1.7 | 0.34 | 6.4 |
| Serum 6 | 80 | 7.62 | 0.17 | 2.2 | 0.47 | 6.1 |
#### Precision results for the HSV-2 Assay
NAª= Not applicable
# Sample matrix
This study was performed on one ADVIA Centaur XP instrument, using 68 sets of matched samples of different matrixes (serum, serum separator tube (SST), EDTA plasma and lithium heparin plasma) from commercial sources.
The samples were analyzed in duplicate in randomized order using one reagent lot.
- . Comparing Serum Separator Tube (y) vs Serum (x): (Deming regression) y = 0.00 + 0.99x, r=0.999, sample range for both matrixes 0.02-9.59 Index Value and 0.02-9.49 Index Value respectively. Note - correlation coefficient is calculated using linear regression.
- Comparing EDTA Plasma(y) vs Serum (x): (Deming regression) y= 0.00 + 0.98 x, ● r=0.998, sample range for both matrixes 0.02-9.59 Index Value and 0.02-9.34 Index Value respectively. Note - correlation coefficient is calculated using linear regression.
- . Comparing Lithium Heparin Plasma(y) vs Serum (x): (Deming regression) y= -0.01 + 0.98 x, r=0.997, sample range for both matrixes 0.02-9.59 Index Value and 0.01-9.23 Index Value respectively. Note - correlation coefficient is calculated using linear regression.
The results supports that Serum Separator Tube is equivalent matrix to Serum, EDTA Plasma is equivalent matrix to Serum and Lithium Heparin Plasma is an equivalent matrix to Serum.
{8}------------------------------------------------
Image /page/8/Picture/0 description: The image contains the logo for Biokit, a Werfen Company. The logo consists of a blue abstract graphic to the left of the text "Biokit". Below the text "Biokit" is the text "A Werfen Company" in a smaller font size. The logo is simple and professional in appearance.
# Panels
The commercial sample panels ToRCH-mixed Zeptometrix and CDC panel were analysed.
The ToRCH-mixed Zeptometrix panel included 24 characterized HSV samples. All of the samples were evaluated with the ADVIA Centaur Herpes-2 IgG assay on ADVIA Centaur XP instrument and 100% total agreement was observed with reference assay 1.
The CDC panel included 100 blind characterized HSV samples. All of the samples were evaluated with the ADVIA Centaur Herpe-2 IgG assay on ADVIA Centaur XP instrument and 100% total agreement was observed in concordance with the results provided by the CDC.
# Interferences
Potential interference in the ADVIA Centaur HSV2 assay from the compounds listed below is designed to be ≤ 10%. Interfering substances at the levels indicated were tested as described in CLSI Document EP7-A2. The testing was done in three levels of samples in the assay range (high negative, low positive and positive samples) with at least one reagent lot on ADVIA Centaur XP instrument.
Testing confirmed no interference (Demonstrate ≤ 10% change in results) for the ADVIA Centaur Herpes-2 IgG up to the following concentrations:
| Serum specimens that are... | Demonstrate ≤10% change in results up to... |
|-----------------------------|---------------------------------------------|
| Biotin | 3500 ng/mL |
| Hemoglobin | 500 mg/dL |
| Bilirubin complex | 40 mg/dL |
| Bilirubin free | 40 mg/dL |
| Hypoproteinemia | 3 g/dL |
| Hyperproteinemia | 12 g/dL |
| Lipemia | 1000 mg/dL |
| Cholesterol | 400 mg/dL |
# Cross-reactivity
The ADVIA Centaur HSV2 assay was evaluated for potential cross-reactivity other viral antibodies, disease-state specimens, and other populations. The HSV-2 IgG status of each specimen was verified using the Comparative Assay. Repeat equivocal specimens on the Comparative Assay were sent to a reference laboratory for Western Blot testing. Total
{9}------------------------------------------------
Image /page/9/Picture/0 description: The image shows the Biokit logo. The logo consists of a blue icon on the left and the word "Biokit" in gray on the right. Below the word "Biokit" is the text "A Werfen Company" in a smaller font size.
percent agreement for the following clinical categories was 96.9% (506/522). The following results were obtained:
| Clinical Category | Number<br>tested | ADVIA Centaur<br>HSV2<br>Reactive | Reference<br>Method<br>Positive | |
|----------------------------------------------------|------------------|-----------------------------------|---------------------------------|---------------------|
| Antibody to hepatitis B surface antigen (Anti-HBs) | 10 | 5 | 6 | |
| Anti-gliadin | 10 | 1 | 1 | |
| Anti-nuclear antibodies (ANA) | 10 | 0 | 1 | |
| Candida albicans | 10 | 3 | 3 | |
| Chlamydia trachomatis | 10 | 4 | 4 | |
| Cytomegalovirus (CMV; HHV-5) | 25 | 9 | 11 | |
| Elevated IgG levels | 10 | 8 | 8 | |
| Elevated IgM levels | 10 | 3 | 3 | |
| Epstein-Barr Virus (EBV IgG) | 10 | 3 | 3 | |
| Escherichia coli | 10 | 5 | 5 | |
| Flu vaccine | 10 | 1 | 1 | |
| Gardenerella vaginalis | 10 | 5 | 5 | |
| Hepatitis B surface antigen (HBsAg) | 10 | 4 | 4 | |
| Hepatitis C Virus (HCV) | 10 | 7 | 7 | |
| Herpes simplex virus type 1 (HSV-1) | 117 | 29 | 31 | |
| Heterophile antibodies (EBV) | 10 | 0 | 0 | |
| Human Anti-mouse antibodies (HAMA) | 10 | 4 | 4 | |
| Human herpes virus 6 (HHV-6) | 10 | 2 | 3 | |
| Human herpes virus 8 (HHV-8) | 10 | 5 | 5 | |
| Human immunodeficiency virus (HIV) | 10 | 9 | 9 | |
| Human Papillomavirus (HPV) | 25 | 3 | 5 | |
| | Number<br>tested | ADVIA Centaur<br>HSV2 | | Reference<br>Method |
| Clinical Category | | Reactive | Positive | |
| Multiple myeloma | 10 | 3 | 3 | |
| Neisseria gonorrhoeae | 10 | 4 | 4 | |
| Parvovirus B19 | 10 | 0 | 0 | |
| Rheumatoid factor (RF) | 10 | 5 | 5 | |
| Rubella IgG | 10 | 2 | 2 | |
| Syphilis | 10 | 7 | 7 | |
| Systemic lupus erythematosus (SLE) | 10 | 1 | 0 | |
| Toxoplasma IgG | 95 | 26 | 30 | |
| Varicella Zoster virus (HHV-3) | 10 | 1 | 1 | |
| Total Samples | 522 | 159 | 171 | |
#### Cross Reactivity Study Performance Results
{10}------------------------------------------------
Biokit
A Werfen Company
### Multisite reproducibility
Reproducibility was evaluated according to the CLSI protocol EP5-A3.25. The ADVIA Centaur HSV2 assay is designed to have reproducibility precision requirements of ≤ 15% for specimens with ≥ 0.80 Index.
A reproducibility study was conducted using 1 reagent lot at 3 external sites on the ADVIA Centaur XP instrument, using a sample panel blinded and randomized that was composed by the Controls (Negative and Positive) and 6 samples prepared at different levels in the assay range.
The protocol was run over 5 days, 2 runs per day, and 3 replicates per run for the sample pools, and for the negative and positive control materials. The data in the following table represents pooled results from the 3 sites.
The results are presented in the table below.
| Specimen<br>type | N | Mean<br>(Index) | Repeatability | | Between-Run | | Between-Day | | Between-Site | | Reproducibility | |
|---------------------|----|-----------------|---------------|------|-------------|------|-------------|------|--------------|------|-----------------|------|
| | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Negative<br>control | 90 | 0.31 | 0.01 | 4.5% | 0.00 | 1.1% | 0.01 | 1.8% | 0.02 | 6.2% | 0.02 | 7.9% |
#### Multisite Precision Study Repeatability
{11}------------------------------------------------
Image /page/11/Picture/0 description: The image contains the logo for Biokit. The logo consists of a blue icon on the left and the word "Biokit" in gray on the right. The icon is made up of two overlapping shapes, one darker blue and one lighter blue. The word "Biokit" is in a sans-serif font.
A Werfen Company
| Specimen<br>type | N | Mean<br>(Index) | Repeatability | | Between-Run | | Between-Day | | Between-Site | | Reproducibility | |
|------------------|----|-----------------|---------------|------|-------------|------|-------------|------|--------------|------|-----------------|------|
| | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Positive control | 90 | 3.27 | 0.06 | 1.9% | 0.04 | 1.2% | 0.04 | 1.4% | 0.06 | 1.8% | 0.10 | 3.2% |
| Serum 1 | 90 | 0.36 | 0.01 | 2.3% | 0.01 | 3.6% | 0.01 | 3.1% | 0.02 | 4.8% | 0.03 | 7.1% |
| Plasma 2 | 90 | 0.64 | 0.01 | 1.8% | 0.01 | 1.1% | 0.02 | 2.7% | 0.00 | 0.0% | 0.02 | 3.4% |
| Serum 3 | 90 | 1.07 | 0.02 | 1.8% | 0.03 | 2.8% | 0.03 | 2.9% | 0.03 | 2.8% | 0.06 | 5.2% |
| Serum 4 | 90 | 2.47 | 0.08 | 3.1% | 0.06 | 2.5% | 0.05 | 1.8% | 0.13 | 5.4% | 0.17 | 7.0% |
| Serum 5 | 90 | 5.24 | 0.34 | 6.4% | 0.12 | 2.3% | 0.11 | 2.2% | 0.21 | 4.0% | 0.43 | 8.2% |
| Serum 6 | 90 | 7.87 | 0.14 | 1.8% | 0.18 | 2.2% | 0.20 | 2.5% | 0.20 | 2.5% | 0.36 | 4.6% |
# Clinical study
A multicenter clinical study to compare the reference device with ADVIA Centaur Herpes-2 IgG was performed. Sensitivity and specificity were determined by comparing the performance of the ADVIA Centaur HSV2 assay to a commercially available anti-HSV-2 IgG immunoblot method (Comparative Assay) and a validated Western Blot reference confirmatory test (University of Washington, Seattle). A total of 864 specimens (≥ 18 years of age), including specimens from 274 pregnant women, were collected within the United States and tested at 3 independent external laboratories. Of these specimens, 254 were reactive, and 610 were nonreactive with the ADVIA Centaur HSV2 assay. The overall agreement was 97.6% (843/864) with a 95% confidence interval (CI) of 96.3%-98.4%. Samples were analyzed in singlicate.
Of the 864 specimens tested by the Comparative Assay, 22 were equivocal and were further tested by the Western Blot test. After Western Blot testing, 20 of the 22 specimens were resolved to be negative and 2 remained equivocal.
| Intended use population | | Comparative Assay<br>Equivocal results have been resolved by Western Blot (WB) | Positive | Negative | Equivocal | Total |
|-------------------------|-------------|--------------------------------------------------------------------------------|----------|----------|-----------|-------|
| ADVIA Centaur HSV2 | Reactive | | 245 | 9 | 0 | 254 |
| | Nonreactive | | 10 | 598 | 2 | 610 |
| | Total | | 255 | 607 | 2 | 864 |
The results obtained for the intended use population are presented below
The sensitivity of the ADVIA Centaur HSV2 assay was 95.3% (245/257), with a 95% confidence interval (CI) of 92.0%-97.3%.
The specificity of the ADVIA Centaur HSV2 assay was 98.5% (598/607), with a 95% confidence interval (CI) of 97.2%-99.2%.
{12}------------------------------------------------
Image /page/12/Picture/0 description: The image contains the logo for Biokit, a Werfen company. The logo consists of a stylized "W" made up of three blue parallelograms, followed by the company name "Biokit" in gray text. Below the company name, the text "A Werfen Company" is written in a smaller, lighter gray font.
Sensitivity and specificity were determined for the pregnant population by comparing the performance of the ADVIA Centaur HSV2 assay to the Comparative Assay and Western Blot confirmatory method. The results of pregnant women samples are presented below:
| Pregnant women | Comparative assay<br>Equivocal results have been resolved by Western Blot (WB) | | | | |
|--------------------|--------------------------------------------------------------------------------|----------|-----------|-------|-----|
| | Positive | Negative | Equivocal | Total | |
| ADVIA Centaur HSV2 | Reactive | 34 | 4 | 0 | 38 |
| | Nonreactive | 0 | 236 | 0 | 236 |
| | Total | 34 | 240 | 0 | 274 |
### Pregnant women Study Contingency (WB resolution) table
The sensitivity of the ADVIA Centaur HSV2 assay was 100.0% (34/34) with a 95% confidence interval of 89.9%—100.0%.
The specificity of the ADVIA Centaur HSV2 assay was 98.3% (236/240) with a 95% confidence interval of 95.8%–99.4%.
#### 10. Stability
The onboard stability of the ADVIA Centaur Herpes-2 IgG reagents is 60 days with a calibration interval of 28 days. The onboard stability of the ADVIA Centaur Herpes-2 IgG Calibrators is 8 hours. The opened vial stability of the ADVIA Centaur Herpes-2 IgG Calibrators is 65 days. Unopened reagents and calibrators are stable until the date printed on the box label when stored at 2-8°C.
#### 11. Conclusion
The analytical and clinical study results demonstrate that the ADVIA Centaur Herpes-2 IgG are substantially equivalent to the predicate device, Focus HerpeSelect 1 and 2 Immunoblot IgG (FDA cleared under K000238), and that the assay is safe and effective for its labeled intended use.
