(94 days)
The ADVIA Centaur® Herpes-1 IgG (HSV1) assay is for in vitro diagnostic use in the qualitative determination of IgG antibodies to herpes simplex virus type 1 (HSV-1) 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-1 infection in the population and the pre-test likelihood of HSV-1 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).
Not Found
The provided text describes the performance study for the ADVIA Centaur Herpes-1 IgG (HSV1) assay, an in vitro diagnostic device. This device is intended for the qualitative determination of IgG antibodies to HSV-1 in human serum and plasma, aiding in the presumptive diagnosis of HSV infection and serological status determination.
The study aims to demonstrate that the device meets its performance requirements, which can be interpreted as acceptance criteria for precision, matrix equivalency, panel agreement, interference, cross-reactivity, and clinical accuracy (sensitivity and specificity).
Here is a breakdown of the requested information:
1. A table of acceptance criteria and the reported device performance
The document implicitly defines acceptance criteria through its "Design Requirement" for precision and agreement percentages for panels, interference, cross-reactivity, and clinical studies.
| Performance Characteristic | Acceptance Criteria (Design Requirement) | Reported Device Performance |
|---|---|---|
| Precision | ||
| Repeatability (%CV) | ||
| Index < 0.5 | NA | 0.01 (SD) for Negative Control (0.26 Index), 0.03 (SD) for Serum 1 (0.25 Index) |
| Index 0.51–0.79 | ≤ 10.0% | 4.8% for Serum 2 (0.57 Index) |
| Index 0.80–1.20 | ≤ 6.0% | 3.1% for Serum 3 (0.97 Index) |
| Index 1.21-3.00 | ≤ 5.0% | 3.2% for Positive Control (2.98 Index), 3.1% for Serum 4 (1.61 Index) |
| Index 3.01-6.00 | ≤ 5.0% | 4.9% for Serum 5 (4.08 Index) |
| Index > 6.00 | ≤ 5.0% | 4.0% for Serum 6 (13.37 Index) |
| Within-Lab (%CV) | ||
| Index < 0.5 | NA | 0.03 (SD) for Negative Control (0.26 Index), 0.04 (SD) for Serum 1 (0.25 Index) |
| Index 0.51–0.79 | ≤ 15.0% | 5.9% for Serum 2 (0.57 Index) |
| Index 0.80–1.20 | ≤ 8.0% | 4.5% for Serum 3 (0.97 Index) |
| Index 1.21-3.00 | ≤ 7.0% | 6.1% for Positive Control (2.98 Index), 5.3% for Serum 4 (1.61 Index) |
| Index 3.01-6.00 | ≤ 7.0% | 6.4% for Serum 5 (4.08 Index) |
| Index > 6.00 | ≤ 10.0% | 7.7% for Serum 6 (13.37 Index) |
| Sample Matrix Equivalence | Demonstrated equivalency with Serum | Correlations from Deming regression: - Serum Separator Tube vs Serum: r=0.996 - EDTA Plasma vs Serum: r=0.998 - Lithium Heparin Plasma vs Serum: r=0.998 |
| Commercial Panel Agreement | Not explicitly stated as a numerical criterion, but high agreement expected. | - Seracare Diagnostics: 92% total agreement with reference assay 1 (25 samples) - ToRCH-mixed Zeptometrix: 96% total agreement with reference assay 1 (24 samples) - CDC panel: 100% total agreement with CDC results (100 samples) |
| Interferences | ≤ 10% change in results with interfering substances | Confirmed ≤ 10% change for various substances up to specified concentrations (e.g., Biotin 3500 ng/mL, Hemoglobin 500 mg/dL) |
| Cross-reactivity | Not explicitly stated as a numerical criterion, but high agreement expected. | 95.8% total agreement (413/431) against Comparative Assay/Western Blot across various clinical categories. |
| Clinical Sensitivity (Overall) | Not explicitly stated, but common for diagnostic tests to aim for high sensitivity/specificity. | 97.5% (507/520) with 95% CI of 95.8%-98.5% |
| Clinical Specificity (Overall) | Not explicitly stated. | 96.2% (331/344) with 95% CI of 93.6%-97.8% |
| Clinical Sensitivity (Pregnant Women) | Not explicitly stated. | 98.7% (155/157) with 95% CI of 95.5%-99.7% |
| Clinical Specificity (Pregnant Women) | Not explicitly stated. | 98.3% (115/117) with 95% CI of 94.0%-99.5% |
2. Sample sizes used for the test set and the data provenance
- Precision Study: 80 replicates per level (for 2 controls and 6 samples). The data provenance is not explicitly stated beyond "performed according to CLSI EP05-A3," suggesting controlled laboratory conditions.
- Sample Matrix Study: 68 sets of matched samples (serum, SST, EDTA plasma, lithium heparin plasma) from "commercial sources." Provenance not explicitly country-specific, but generally implies a controlled study.
- Panels Study:
- Seracare Diagnostics panel: 25 characterized HSV samples.
- ToRCH-mixed Zeptometrix panel: 24 characterized HSV samples.
- CDC panel: 100 blind characterized HSV samples.
- Provenance: Commercial sources and CDC (likely US-based).
- Interferences Study: Not specified, but involved testing at three levels of samples for each interfering substance.
- Cross-reactivity Study: 431 specimens across various clinical categories. Provenance not specified.
- Clinical Study:
- Sample Size: 864 specimens (total enrollment)
- Provenance: "Collected within the United States" and tested at "3 independent external laboratories." This indicates a prospective collection for the clinical study.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
The document does not specify the number of experts or their qualifications for establishing ground truth.
- For the panel studies, "characterized HSV samples" from commercial sources and "blind characterized HSV samples" from the CDC were used. This implies that the ground truth for these samples was established by the respective commercial supplier or the CDC, likely through a validated reference method, but the specific expertise of those who characterized them is not detailed.
- For the cross-reactivity study, the HSV-1 IgG status of specimens was verified using a "Comparative Assay" (a commercially available anti-HSV-1 IgG immunoblot method) and, for equivocal cases, a "validated Western Blot reference confirmatory test (University of Washington, Seattle)." This points to a recognized reference laboratory (University of Washington) for confirmatory testing, but the specific experts (e.g., medical technologists, scientists, physicians) and their qualifications involved in interpreting these reference methods are not stated.
- For the clinical study, the ground truth was established by comparing the device's performance to a "commercially available anti-HSV-1 IgG immunoblot method (Comparative Assay)" and a "validated Western Blot reference confirmatory test (University of Washington, Seattle)" for equivocal results. Again, the specific experts involved in the interpretation of these reference methods are not detailed.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
The document states that for the clinical study, 22 "equivocal" results from the Comparative Assay were "further tested by the Western Blot test." This serves as a form of adjudication, where a higher-level, confirmed reference method (Western Blot) resolves uncertain or equivocal results from the primary comparative method. It's not a multi-reader, consensus-based adjudication, but rather a hierarchical resolution using a more definitive test.
5. 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
No, this is not a multi-reader multi-case (MRMC) comparative effectiveness study. The device reviewed is an in vitro diagnostic assay (HSV-1 IgG antibody test), not an AI-based imaging or interpretive software that would be used by human readers. Therefore, the concept of human readers improving with AI assistance is not applicable to this device.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the studies presented (precision, matrix, panels, interference, cross-reactivity, and clinical sensitivity/specificity) reflect the standalone performance of the ADVIA Centaur HSV1 assay as an automated in vitro diagnostic device. Its output (qualitative determination of IgG antibodies) is directly provided by the instrument based on its chemical reactions and detector, without a human-in-the-loop directly influencing the test result. Human intervention would be for specimen handling, loading, and result review, but not for the determination of the assay's output itself.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
The ground truth for this in vitro diagnostic device was established primarily through:
- Reference Assays/Methods:
- A "reference assay 1" for commercial panels.
- "Results provided by the CDC" for the CDC panel.
- A "commercially available anti-HSV-1 IgG immunoblot method (Comparative Assay)" and a "validated Western Blot reference confirmatory test (University of Washington, Seattle)" for the clinical and cross-reactivity studies.
- This falls under the category of reference standard comparison using established laboratory methods believed to be highly accurate.
8. The sample size for the training set
The document describes performance studies for regulatory submission (510(k)). It does not provide information about a "training set" in the context of machine learning, as this is an immunoassay, not an AI/ML-based device. If "training set" refers to samples used during the assay's development or optimization prior to these validation studies, that information is not provided in this regulatory summary. The presented data represents the validation/test set.
9. How the ground truth for the training set was established
As there is no mention of a "training set" in the context of an AI/ML device, this question is not applicable. The assay's performance relies on its biochemical design and manufacturing controls, not on a machine learning model that requires a ground-truth-labeled training set.
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August 23, 2018
Biokit, S.A. Joan Guixer QA & RA Director Can Male S/N Llica d'Amunt, 08186 Barcelona, Spain
Re: K181333
Trade/Device Name: ADVIA Centaur Herpes-1 IgG Regulation Number: 21 CFR 866.3305 Regulation Name: Herpes simplex virus serological assays Regulatory Class: Class II Product Code: MXJ Dated: May 17, 2018 Received: May 25, 2018
Dear Joan Guixer:
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 statutes and regulations administered by other Federal agencies. You must comply with all the Act's
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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.htm); 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
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Indications for Use
510(k) Number (if known) K181333
Device Name ADVIA Centaur Herpes-1 IgG
Indications for Use (Describe)
The ADVIA Centaur® Herpes-1 IgG (HSV1) assay is for in vitro diagnostic use in the qualitative determination of IgG antibodies to herpes simplex virus type 1 (HSV-1) 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-1 infection in the population and the pre-test likelihood of HSV-1 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) | |
|---|---|
| ✖ 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 Information | Biokit, S.A.Can Malé S/NLliçà d'Amunt 08186Barcelona (Spain) |
|---|---|
| ---------------------------- | -------------------------------------------------------------------------- |
| 2. Contact Person | Joan Guixer, QA & RA DirectorPhone: +34 93 860 90 00 / +34 657 88 33 47Email: jguixer@biokit.com |
|---|---|
| ------------------- | ---------------------------------------------------------------------------------------------------------- |
| 3. Preparation Date | May 17th, 2018 |
|---|---|
| --------------------- | ---------------- |
| 5. RegulatoryInformation | Regulation Number | 21 CFR 866.3305 |
|---|---|---|
| Regulation Description | Herpes simplex virusserological assays. | |
| Classification | Class II Special Controls | |
| Product Code | MXJ | |
| Classification Panel | Microbiology |
| 6. Predicate Device | K000238 (Focus HerpeSelect 1 and 2 Immunoblot IgG) |
|---|---|
| --------------------- | ---------------------------------------------------- |
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| 7. Indications for Use /Intended Use | The ADVIA Centaur Herpes-1 IgG (HSV1) assay is for in vitro diagnostic use in the qualitative determination of IgG antibodies to herpes simplex virus type 1 (HSV-1) in human serum and plasma (EDTA and lithium heparin) using the ADVIA Centaur systems. This assay is intended for use as an aid in the determination of serological status to HSV-1 and in the diagnosis of herpes simplex virus infection. |
|---|---|
| -------------------------------------------------- | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ |
| COMPARISON PREDICATE | ||
|---|---|---|
| Item | Predicate | New Device |
| Trade Names | Focus HerpeSelect 1 and 2Immunoblot IgG | ADVIA Centaur Herpes-1 IgG |
| 510K nº | K000238 | Pending |
| Manufacturer | Focus DiagnosticCypress, CA 90630 -USA | Siemens HeathcareDiagnostics Inc.511 Benedict Avenue,Tarrytown, NY 10591- USA |
| Similarities | ||
| Intended use | Focus Diagnostics HerpeSelect 1and 2 Immunoblot IgG test is | The ADVIA Centaur Herpes-1IgG (HSV1) assay is for in vitro |
| intended for qualitatively detectingthe presence or absence of humanIgG class antibodies to HSV-1 andHSV-2 in human sera. The test isindicated for testing sexually activeadults or expectant mothers foraiding in the presumptive diagnosisof HSV-1 and HSV-2 infection. Thepredictive value of a positive ornegative result depends on thepopulation's prevalence and thepretest likelihood of HSV- 1 andHSV-2 infection. The performanceof this assay has not beenestablished for use in a pediatricpopulation, for neonatal screening,for testing ofimmunocompromised patients, foruse by a point of care facility or foruse with automated equipment | diagnostic use in thequalitative determination ofIgG antibodies to herpessimplex virus type 1 (HSV-1)in human serum and plasma(EDTA and lithium heparin)using the ADVIA Centaursystems. This assay isintended for use as an aid inthe determination ofserological status to HSV-1and in the diagnosis ofherpes simplex virusinfection. | |
| Measurand | To detect the presence or absenceof human IgG class antibodies toHSV-1 and HSV-2 | To detect IgG antibodies toherpes simplex virus type 1(HSV-1). |
| Regulation Section | 21 CFR 866.3305 | Same |
| Product Code | LGC | MXJ |
| Classification | Class II Special Controls | Same |
| Assay Type | Qualitative | Same |
| Differences | ||
| Technology | Nitrocellulose immunoblot | Chemiluminescentimmunoassay |
| Sample type | Human serum | Human serum andplasma (EDTA and lithiumheparin) |
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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 HSV1 assay is designed to have the following repeatability and withinlab precision requirements:
| Design Requirement | ||
|---|---|---|
| ADVIA Centaur HSV1 Level (Index) | Repeatability% CV | Within-Lab% 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% | ≤ 7.0% |
| 3.01-6.00 | ≤ 5.0% | ≤ 7.0% |
| > 6.00 | ≤ 5.0% | ≤ 10.0% |
೩ NA = not applicable
The results for this study are presented below.
| Specimen Type | N | Mean(Index) | Repeatability | Within-Lab | ||
|---|---|---|---|---|---|---|
| SD | CV (%) | SD | CV(%) | |||
| Negative Control(Plasma) | 80 | 0.26 | 0.01 | NAa | 0.03 | NAa |
| Positive Control(Plasma) | 80 | 2.98 | 0.10 | 3.2 | 0.18 | 6.1 |
| Serum 1 | 80 | 0.25 | 0.03 | NAa | 0.04 | NAa |
| Serum 2 | 80 | 0.57 | 0.03 | 4.8 | 0.03 | 5.9 |
| Serum 3 | 80 | 0.97 | 0.03 | 3.1 | 0.04 | 4.5 |
| Serum 4 | 80 | 1.61 | 0.05 | 3.1 | 0.09 | 5.3 |
| Serum 5 | 80 | 4.08 | 0.20 | 4.9 | 0.26 | 6.4 |
| Serum 6 | 80 | 13.37 | 0.53 | 4.0 | 1.04 | 7.7 |
Precision results for the HSV-1 Assay
NA = Not applicable
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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 = -0.01 + 0.99 x, r=0.996, sample range for both matrixes 0.10-19.15 Index Value and 0.10-19.59 Index Value respectively. Note – correlation coefficient is calculated using linear regression.
- . Comparing EDTA Plasma(y) vs Serum (x): (Deming regression) y= -0.02 + 0.96 x, r=0.998, sample range for both matrixes 0.10-19.14 Index Value and 0.11-19.19 Index Value respectively. Note - correlation coefficient is calculated using linear regression.
- . Comparing Lithium Heparin Plasma(y) vs Serum (x): (Deming regression) y= -0.02 + 0.96 x, r=0.998, sample range for both matrixes 0.10-19.15 Index Value and 0.10-18.73 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.
Panels
The commercial sample panels, Seracare Diagnostics and ToRCH-mixed Zeptometrix, and CDC panel were analysed.
The Seracare Diagnostics panel included 25 characterized HSV samples. All of the samples were evaluated with the ADVIA Centaur Herpes-1 IgG assay on ADVIA Centaur XP instrument and 92% total agreement was observed with reference assay 1.
The ToRCH-mixed Zeptometrix panel included 24 characterized HSV samples. All of the samples were evaluated with the ADVIA Centaur Herpes-1 IgG assay on ADVIA Centaur XP instrument and 96% 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 Herpes-1 IgG assay on ADVIA Centaur XP instrument and 100% total agreement was observed in concordance with the results provided by the CDC.
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Interferences
Potential interference in the ADVIA Centaur HSV1 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-1 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 HSV1 assay was evaluated for potential cross-reactivity with other viral antibodies, disease-state specimens, and other populations. The HSV-1 lgG 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 percent agreement for the following clinical categories was 95.8% (413/431). The following results were obtained:
Cross Reactivity Study Performance Results
| Number | ADVIA Centaur HSV1 | Comparative Assay | ||
|---|---|---|---|---|
| Clinical Category | tested | Reactive | Positive | |
| Antibody to hepatitis B surface antigen (Anti-HBs) | 10 | 8 | 8 | |
| Anti-gliadin | 10 | 6 | 6 | |
| Anti-nuclear antibody (ANA) | 10 | 5 | 5 | |
| Clinical Category | Number tested | ADVIA Centaur HSV1Reactive | Comparative AssayPositive | |
| Candida albicans | 10 | 10 | 9 | |
| Chlamydia trachomatis | 10 | 6 | 7a | |
| Cytomegalovirus (CMV IgG) | 10 | 6 | 7b | |
| Elevated IgG | 10 | 8 | 8 | |
| Elevated IgM | 10 | 9 | 10a/c | |
| Epstein-Barr virus (EBV VCA IgG) | 10 | 9 | 9 | |
| Escherichia coli | 10 | 9 | 9 | |
| Flu vaccine recipients | 10 | 3 | 3 | |
| Gardnerella vaginalis | 10 | 7 | 7 | |
| Hepatitis C virus (HCV) | 25 | 19 | 21 | |
| Hepatitis B surface antigen (HBsAg) | 10 | 9 | 9 | |
| Herpes simplex virus type 2 (HSV-2) | 74 | 35 | 33a | |
| Heterophile antibodies | 10 | 1 | 1 | |
| Human anti-mouse antibody (HAMA) | 31 | 24 | 25a | |
| Human herpes virus 6 (HHV-6) | 10 | 6 | 5 | |
| Human herpes virus 8 (HHV-8) | 10 | 9 | 9 | |
| Human immunodeficiency virus (HIV) | 10 | 10 | 10 | |
| Human Papillomavirus (HPV) | 10 | 6 | 6a | |
| Multiple myeloma | 10 | 10 | 10 | |
| Neisseria gonorrhoeae | 25 | 17 | 16 | |
| Parvovirus B19 | 10 | 4 | 4 | |
| Rheumatoid Factor (RF) | 10 | 6 | 6 | |
| Rubella IgG | 10 | 7 | 7 | |
| Syphilis | 10 | 9 | 9a | |
| Systemic lupus erythematosus (SLE) | 26 | 17 | 17 | |
| Toxoplasma IgG | 10 | 10 | 10 | |
| Varicella zoster virus (VZV) | 10 | 5 | 6a | |
| Total Specimens | 431 | 290 | 292 |
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A Werfen Company
ª One sample was confirmed positive by Western Blot
Ь One sample was confirmed positive by Comparative Assay
< Two samples were confirmed positive by Comparative Assay
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Clinical study
A multisite clinical study to compare the reference with ADVIA Centaur Herpes-1 lgG was performed. Sensitivity and specificity were determined by comparing the performance of the ADVIA Centaur HSV1 assay to a commercially available anti-HSV-1 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. Samples were analyzed in singlicate. Of these specimens, 520 were reactive, and 344 were nonreactive with the ADVIA Centaur HSV1 assay. The overall agreement was 97.0% (838/864) with a 95% confidence interval (CI) of 95.6%-97.9%.
Of the 864 specimens tested by the Comparative Assay, 22 were equivocal and further tested by the Western Blot test. After Western Blot testing, 19 of the specimens were resolved to be negative and 3 remained equivocal.
| Intended use population | Comparative Assay.Equivocal results have been resolved by Western Blot (WB) | ||||
|---|---|---|---|---|---|
| Positive | Negative | Equivocal | Total | ||
| ADVIA Centaur HSV1 | Reactive | 507 | 13 | 0 | 520 |
| Nonreactive | 10 | 331 | 3 | 344 | |
| Total | 517 | 344 | 3 | 864 |
The results obtained for the intended use population are presented below
The sensitivity of the ADVIA Centaur HSV1 assay was 97.5% (507/520), with a 95% confidence interval (CI) of 95.8%-98.5%.
The specificity of the ADVIA Centaur HSV1 assay was 96.2% (331/344), with a 95% confidence interval (CI) of 93.6%-97.8%.
Sensitivity and specificity were determined for the pregnant population by comparing the performance of the ADVIA Centaur HSV1 assay to the Comparative Assay and Western Blot confirmatory method.The results of the pregnant women samples are presented below:
| Pregnant women | Comparative AssayEquivocal results have been resolved by Western Blot (WB) | ||||
|---|---|---|---|---|---|
| ADVIA Centaur HSV1 | Reactive | 155 | 2 | 0 | 157 |
| Nonreactive | 2 | 115 | 0 | 117 | |
| Total | 157 | 117 | 0 | 274 |
Pregnant women Study Contingency (WB resolution) table
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The sensitivity of the ADVIA Centaur HSV1 assay was 98.7% (155/157) with a 95% confidence interval of 95.5%-99.7%.
The specificity of the ADVIA Centaur HSV1 assay was 98.3% (115/117) with a 95% confidence interval of 94.0%-99.5%.
10. Stability
The onboard stability of the ADVIA Centaur Herpes-1 IgG reagents is 60 days with a calibration interval of 28 days. The onboard stability of the ADVIA Centaur Herpes-1 IgG Calibrators is 8 hours. The opened vial stability of the ADVIA Centaur Herpes-1 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-1 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.
§ 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).