(272 days)
The ADVIA Centaur EBV-EBNA IgG (EBVnaG) assay is for in vitro diagnostic use in the qualitative detection of IqG antibodies to Epstein-Barr virus (EBV) nuclear antigen (EBNA) in human pediatric (2-21 years old) and adult serum and plasma (EDTA and lithium heparin) using the ADVIA Centaur XP system. When used in conjunction with other EBV markers, this assay is intended for use as an aid in the diagnosis of Epstein-Barr virus infection, such as infectious mononucleosis.
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The provided text describes the performance of the ADVIA Centaur EBV-EBNA IgG assay, an in vitro diagnostic device for the qualitative detection of IgG antibodies to Epstein-Barr virus (EBV) nuclear antigen (EBNA).
Here's an analysis of the acceptance criteria and study data:
1. Acceptance Criteria and Reported Device Performance
The acceptance criteria for the ADVIA Centaur EBV-EBNA IgG assay are primarily demonstrated through its agreement with an FDA-cleared reference EBV EBNA IgG assay. While explicit "acceptance criteria" are not listed with numerical thresholds in a dedicated table, the clinical study results (Positive Percent Agreement - PPA and Negative Percent Agreement - NPA) are implicitly compared against an expectation of substantial equivalence to the predicate device.
For precision and reproducibility, specific targets are mentioned.
| Performance Metric | Acceptance Criteria (Implied/Stated) | Reported Device Performance |
|---|---|---|
| Clinical Study | Substantial Equivalence to Predicate Device (LIAISON EBNA IgG) | Population 1 (Total Study Population - symptomatic individuals)- NPA: 92.8% (95% CI: 89.6% - 95.1%)- PPA: 99.4% (95% CI: 98.8% - 99.7%)Population 2 (Known EBV EBNA IgG negative individuals)- NPA: 98.2% (95% CI: 94.9% - 99.4%)Pediatric Population (Population 1 - symptomatic)- NPA: 97.3% (95% CI: 94.3% - 98.8%)- PPA: 98.4% (95% CI: 96.0% - 99.4%)Pediatric Population (Population 2 - known negative)- NPA: 100% (95% CI: 94.9% - 100%) |
| Precision | Not explicitly stated as a single value, but individual sample CVs are presented. | Serum Samples: Total Precision CVs range from 4.4% to 13.3%.Plasma, EDTA Samples: Total Precision CVs range from 4.3% to 9.5%.Controls: Control 1 (0.32 Index) Total Precision SD 0.014; Control 2 (3.16 Index) Total Precision CV 4.1%. |
| Reproducibility | - Concentration $\le$ 0.80 Index: N/A (for CV)- Concentration > 0.80 Index: $\le$ 20.0% CV | Serum Samples:- Serum A (0.77 Index): SD 0.048, CV N/A (within $\le$ 0.80 Index)- Serum B-E (1.07 to 8.85 Index): CVs range from 4.0% to 9.8% (all $\le$ 20.0%)Plasma, EDTA Samples:- Plasma A (0.78 Index): SD 0.044, CV N/A (within $\le$ 0.80 Index)- Plasma B-E (1.06 to 8.75 Index): CVs range from 5.0% to 10.7% (all $\le$ 20.0%)Controls: Control 1 (0.36 Index) SD 0.022, CV N/A; Control 2 (3.31 Index) CV 4.0%. |
| Specimen Equivalency | Regression equation close to y=x, high correlation coefficient (r). | EDTA Plasma vs. Serum: y = 1.00x - 0.01 Index; r = 1.00Lithium Heparin Plasma vs. Serum: y = 0.98x - 0.01 Index; r = 0.99Conclusion: EDTA Plasma and Lithium Heparin Plasma are equivalent matrixes to Serum. |
| Interferences | $\pm$10% bias for reactive samples and $\pm$0.10 Index for nonreactive samples. | The listed substances (Hemoglobin, Bilirubin, Lipemia, Biotin, Cholesterol, Protein, etc.) do not interfere at the indicated concentrations. |
| Cross-reactivity | Not explicitly stated as a numerical criterion, but demonstrated by testing against various viral antibodies and disease states. | Data presented for 330 samples across 29 clinical categories, showing agreement or defined discrepancies with the comparative assay. For HCV, Mycoplasma pneumoniae IgG, HSV-1 IgG, and HSV-2 IgG, possible cross-reactivity cannot be excluded for a few discordant samples and should be interpreted clinically. |
| Onboard Stability | 28 days for reagents, 28 days for calibration. | Reagents: 28 days. Calibration: 28 days. |
| Calibrator Stability (Opened Vial) | 60 days when stored at 2-8ºC. | 60 days when stored at 2-8ºC. |
| Unopened Reagents/Calibrators Stability | Until expiration date when stored at 2-8°C. | Until expiration date when stored at 2-8°C. |
2. Sample Size and Data Provenance
Clinical Study (Test Set):
- Total Study Population (Population 1): 1428 leftover samples.
- Provenance: Collected over a contiguous time period from individuals for whom an EBV test was ordered. The document does not specify the country of origin but implies a clinical setting ("symptoms and signs for whom an EBV antibody test was ordered"). It is a retrospective collection of leftover samples.
- Known EBV EBNA IgG Negative Population (Population 2): 167 samples.
- Provenance: Samples with a known EBV EBNA IgG negative result, used to supplement numbers for negative EBV EBNA IgG. Retrospective.
- Pediatric Population: Subsets of Population 1 (479 samples including 84 unclassified serostatus individuals) and Population 2 (72 samples including 6 unclassified serostatus individuals).
- Cross-reactivity Study: 330 samples across various clinical categories.
- Specimen Equivalency Study: 97-98 sets of matched samples (SST, EDTA plasma, lithium heparin plasma).
- Provenance: Commercial sources.
3. Number of Experts and Qualifications for Ground Truth
The document explicitly states that the ground truth for the clinical study was established by an "FDA cleared EBV EBNA IgG reference assay."
It also states: "Equivocal reference assay results were resolved by 2 other comparative assays."
- Number of 'Experts' (resolving assays): 2 (for equivocal cases from the primary reference assay).
- "Qualifications" of these 'experts': These were "comparative assays" rather than human experts. The document does not specify if these were other FDA-cleared assays or the nature of their qualification, but the implication is that they served as a consensus mechanism to resolve indeterminate results from the primary reference assay.
4. Adjudication Method for the Test Set
The adjudication method for equivocal results from the primary reference assay was by "2 other comparative assays." This is a form of 2+0 or 1+2 (primary reference + 2 comparative). If the two comparative assays agreed, that likely established the reconciled ground truth for the equivocal samples. The document does not describe what happened if the two comparative assays disagreed.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No MRMC comparative effectiveness study was done. This device is an in vitro diagnostic assay, which typically does not involve human readers interpreting images or data alongside AI. The device is evaluated for its analytical and clinical performance against a reference method. Therefore, there is no information on how much human readers improve with AI vs. without AI assistance.
6. Standalone (Algorithm only without human-in-the loop performance)
Yes, a standalone performance study was done. The entire clinical study, precision, reproducibility, specimen equivalency, and interference studies evaluate the performance of the ADVIA Centaur EBV-EBNA IgG assay as a standalone device (algorithm/assay only) against a reference method or predetermined analytical specifications. There is no human-in-the-loop component described for its primary intended use and evaluation.
7. Type of Ground Truth Used
The ground truth used for the clinical study was based on an FDA-cleared EBV EBNA IgG reference assay, with equivocal results resolved by 2 other comparative assays. This indicates a reference method or comparative assay-based ground truth.
8. Sample Size for the Training Set
The document is a 510(k) summary for an in vitro diagnostic assay. It does not provide information regarding a "training set" in the context of machine learning or AI models.
The samples mentioned are for performance evaluation (clinical study, precision, etc.) and are analogous to test or validation sets. For IVD devices, a "training set" might refer to samples used during the development and optimization of the assay's reagents and parameters, but this information is not typically disclosed in a 510(k) summary in this format.
9. How the Ground Truth for the Training Set Was Established
As there is no "training set" described in the context of an AI/ML model for this IVD assay according to the provided document, this information is not applicable and not available.
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August 07, 2024
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Biokit S.A. Dominique Monferrer Regulatory Affairs Director Av. Can Montcau 7 Llicà d'Amunt. 08186 Spain
Re: K233605
Trade/Device Name: ADVIA Centaur EBV-EBNA IgG Regulation Number: 21 CFR 866.3235 Regulation Name: Epstein-Barr Virus Serological Reagents Regulatory Class: Class I, reserved Product Code: LLM, LSE Dated: July 29, 2024 Received: July 29, 2024
Dear Dominique Monferrer:
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/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.
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" (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).
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Your device is also subject to, among other requirements, the Quality System (OS) 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 QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 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.
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 mediation-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).
Sincerely,
Bhawna Poonia -S
for Maria Garcia, Ph.D. Assistant Director Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration
Indications for Use
Submission Number (if known)
Device Name
ADVIA Centaur EBV-EBNA IgG (10720840)
| Indications for Use (Describe) | |
|---|---|
| -------------------------------- | -- |
The ADVIA Centaur EBV-EBNA IgG (EBVnaG) assay is for in vitro diagnostic use in the qualitative detection of IqG antibodies to Epstein-Barr virus (EBV) nuclear antigen (EBNA) in human pediatric (2-21 years old) and adult serum and plasma (EDTA and lithium heparin) using the ADVIA Centaur XP system. When used in conjunction with other EBV markers, this assay is intended for use as an aid in the diagnosis of Epstein-Barr virus infection, such as infectious mononucleosis.
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'sInformation | Biokit, S.A.Av. Can Montcau, 7Lliçà d'Amunt 08186Barcelona (Spain) |
|---|---|
| ------------------------------- | -------------------------------------------------------------------------------- |
| 2. Contact Person | Dominique Monferrer, Regulatory Affairs DirectorPhone: +34 93 860 90 00Email: dmonferrer@werfen.com |
|---|---|
| ------------------- | ------------------------------------------------------------------------------------------------------------- |
| 3. Preparation Date | 2023-Nov-09 |
|---|---|
| --------------------- | ------------- |
| 4. Device TradeName | ADVIA Centaur EBV-EBNA IgG |
|---|---|
| -------------------------- | ---------------------------- |
| Regulation Number | 21 CFR 866.3235 |
|---|---|
| Regulation Description | Epstein-Barr Virus serological reagents |
| 5. Regulatory Information | |
| Classification | Class I (general controls) |
| Product Code | LLM, LSE |
| Classification Panel | Microbiology |
| 6. Predicate Device | K040120 (LIAISON EBNA IgG) |
|---|---|
| --------------------- | ---------------------------- |
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| 7. Indications forUse / IntendedUse | The ADVIA Centaur EBV-EBNA IgG (EBVnaassay is for in vitro diagnostic use in thqualitative detection of IgG antibodies to EpsteiBarr virus (EBV) nuclear antigen (EBNA)human pediatric (2-21 years old) and aduserum and plasma (EDTA and lithium hepariusing the ADVIA Centaur XP system. When usein conjunction with other EBV markers, this assais intended for use as an aid in the diagnosis ofEpstein-Barr virus infection, such as infectioumononucleosis |
|---|---|
| ------------------------------------------------------ | ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- |
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| COMPARISON PREDICATE | ||
|---|---|---|
| Item | Predicate | New Device |
| Trade Names | LIAISON EBNA IgG | ADVIA Centaur EBV-EBNAIgG |
| 510K no. | K040120 | K233605 |
| Manufacturer | DiaSorin, S.p.A.Via Crescentino, snc13040 Saluggia (Vercelli) Italy | Siemens HealthcareDiagnostics Inc.511 Benedict Avenue,Tarrytown, NY 10591 USA |
| Intended use | The LIAISON EBNA IgG assayuses chemiluminescentimmunoassay (CLIA)technology on the LIAISONAnalyzer family* for thequalitative determination ofspecific IgG antibodies toEpstein-Barr virus (EBV)nuclear antigen syntheticpeptide (EBNA-1) in humanserum. When performed inconjunction with other EBVmarkers, this assay can beused as an aid in the clinicallaboratory diagnosis of Epstein-Barr Viral Syndrome in patientswith signs and symptoms ofEBV infection such as infectiousmononucleosis.*(LIAISON and LIAISON XL) | The ADVIA Centaur EBV-EBNA IgG assay is for invitro diagnostic use in thequalitative detection of IgGantibodies to Epstein-Barrvirus (EBV) nuclear antigen(EBNA) in human pediatric(2-21 years old) and adultserum and plasma (EDTAand lithium heparin) usingthe ADVIA Centaur XPsystem. When used inconjunction with other EBVmarkers, this assay isintended for use as an aid inthe diagnosis of Epstein-Barrvirus infection, such asinfectious mononucleosis. |
| Similarities | ||
| Measurand | Specific IgG antibodies toEpstein-Barr virus (EBV)nuclear antigen syntheticpeptide (EBNA-1). | To detect IgG antibodies tothe Epstein-Barr virus (EBV)nuclear antigen (EBNA). |
| RegulationSection | 21 CFR 866.3235 | Same |
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| Product Code | LLM, LSE | Same |
|---|---|---|
| Classification | Class I (general controls) | Same |
| Assay Type | Qualitative | Same |
| Technology | Chemiluminescentimmunoassay (CLIA) | Same |
| Antigen | EBNA-1 | Same |
| Differences | ||
| Sample type | Human serum | Human serum and plasma(EDTA and lithium heparin) |
| TargetPopulation | Adults | Pediatric and adult |
9. Performance Summary
Clinical Study
A multisite clinical study to compare the reference method with ADVIA Centaur EBV-EBNA IgG was performed.
Comparison of Results: Total Study Population
A total of 1428 leftover samples were collected over a contiguous time period from individuals for whom an EBV test was ordered (population 1). Of these, 188 were from unclassified serostatus individuals. One-hundred sixty-seven (167) samples with a known EBV EBNA IgG negative result (population 2) were evaluated as well. Of these, 14 were from unclassified serostatus individuals. The study results otherwise showed that these populations included individuals with acute infection, past infection, or no serologic evidence of EBV infection.
Samples were tested using the ADVIA Centaur EBVnaG assay and an FDA cleared EBV EBNA IgG reference assay. Equivocal reference assay results were resolved by 2 other comparative assays. The results obtained are presented in the following tables:
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| Population 1 | ||||
|---|---|---|---|---|
| ADVIA CentaurEBVnaG Assay | Reference Assay | |||
| Negative | Equivocal | Positive | Total | |
| Nonreactive | 323 | 2 | 4 | 329 |
| Reactive | 23 | 2 | 1074 | 1099 |
| Total | 346 | 4 | 1078 | 1428 |
| NPAa=92.8% | PPAc=99.4% | |||
| (323/348) | (1074/1080) | |||
| 95% CIb: 89.6% -95.1% | 95% CI: 98.8% -99.7% |
a Negative percent agreement.
b Confidence interval.
C Positive percent agreement.
| Population 2 | ||||
|---|---|---|---|---|
| ADVIA CentaurEBVnaG Assay | Reference Assay | |||
| Negative | Equivocal | Positive | Total | |
| Nonreactive | 164 | 0 | 0 | 164 |
| Reactive | 3 | 0 | 0 | 3 |
| Total | 167 | 0 | 0 | 167 |
| NPAa=98.2% (164/167) | N/Ac | |||
| 95% CIb: 94.9% - 99.4% |
a Negative percent agreement.
b Confidence interval.
C Not applicable.
Percent of Agreement: Pediatric Population
The agreement between the ADVIA Centaur EBVnaG assay and the reference EBV EBNA IgG assay in the pediatric subjects from Population 1 and 2 is presented in the tables below. Population 1 included samples from subjects with signs and symptoms for whom an EBV antibody test was ordered. Of these, 84 were unclassified serostatus individuals. The study results showed that this population included individuals with acute, past, or no serologic evidence of EBV infection. Population 2 included samples with a known EBV EBNA IgG negative result to supplement numbers for negative EBV EBNA IgG. Of these, 6 were unclassified serostatus individuals.
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| Population 1 | ||||
|---|---|---|---|---|
| ADVIA CentaurEBVnaG Assay | Negative | Equivocal | Positive | Total |
| Nonreactive | 220 | 2 | 2 | 224 |
| Reactive | 5 | 1 | 249 | 255 |
| Total | 225 | 3 | 251 | 479 |
| NPAa=97.3%(220/226)95% CIb: 94.3% -98.8% | PPAc=98.4%(249/253)95% CI: 96.0% -99.4% |
a Negative percent agreement.
b Confidence interval.
് Positive percent agreement.
| Population 2 | ||||
|---|---|---|---|---|
| ADVIA CentaurEBVnaG Assay | Negative | Equivocal | Positive | Total |
| Nonreactive | 72 | 0 | 0 | 72 |
| Reactive | 0 | 0 | 0 | 0 |
| Total | 72 | 0 | 0 | 72 |
| NPAa=100% (72/72)95% CIb: 94.9% - 100% | N/Ac |
a Negative percent agreement.
b Confidence interval.
° Not applicable.
Precision
Precision was determined in accordance with CLSI EP05-A3 using the Negative and Positive Controls as well as 5 serum samples and 5 EDTA plasma samples prepared at different levels across the assay range. Samples (N=240) were assayed in replicates of 2 with 2 runs per day using three reagent lots in a 20day protocol.
The following results are representative of the performance of the assay:
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| Sample | Mean Value(Index) | Repeatability | Between Run | Between Day | Between Lot | Total Precision | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| SDb(Index) | CVc(%) | SD(Index) | CV(%) | SD(Index) | CV(%) | SD(Index) | CV(%) | SD(Index) | CV(%) | ||
| SerumA | 0.69 | 0.015 | 2.1 | 0.026 | 3.8 | 0.000 | 0.0 | 0.006 | 0.9 | 0.030 | 4.4 |
| SerumB | 1.01 | 0.019 | 1.8 | 0.029 | 2.8 | 0.000 | 0.0 | 0.092 | 9.0 | 0.098 | 9.7 |
| SerumC | 1.34 | 0.024 | 1.8 | 0.029 | 2.2 | 0.047 | 3.5 | 0.167 | 12.5 | 0.178 | 13.3 |
| SerumD | 4.98 | 0.074 | 1.5 | 0.084 | 1.7 | 0.166 | 3.3 | 0.326 | 6.5 | 0.382 | 7.7 |
| SerumE | 8.54 | 0.164 | 1.9 | 0.195 | 2.3 | 0.145 | 1.7 | 0.187 | 2.2 | 0.348 | 4.1 |
| Plasma,EDTA A | 0.71 | 0.015 | 2.1 | 0.024 | 3.4 | 0.005 | 0.7 | 0.009 | 1.3 | 0.030 | 4.3 |
| Plasma,EDTA B | 0.95 | 0.019 | 2.1 | 0.028 | 2.9 | 0.009 | 0.9 | 0.083 | 8.8 | 0.090 | 9.5 |
| Plasma,EDTA C | 1.33 | 0.025 | 1.9 | 0.047 | 3.6 | 0.021 | 1.6 | 0.000 | 0.0 | 0.058 | 4.3 |
| Plasma,EDTA D | 4.93 | 0.108 | 2.2 | 0.122 | 2.5 | 0.132 | 2.7 | 0.121 | 2.5 | 0.242 | 4.9 |
| Plasma,EDTA E | 8.76 | 0.155 | 1.8 | 0.239 | 2.7 | 0.116 | 1.3 | 0.254 | 2.9 | 0.399 | 4.6 |
| Control1 | 0.32 | 0.007 | N/Ac | 0.007 | N/A | 0.009 | N/A | 0.006 | N/A | 0.014 | N/A |
| Control2 | 3.16 | 0.051 | 1.6 | 0.065 | 2.1 | 0.079 | 2.5 | 0.061 | 1.9 | 0.130 | 4.1 |
a Standard deviation.
b Coefficient of variation.
് Not Applicable.
Reproducibility
Reproducibility was determined in accordance with CLSI EP05-A3. Testing was performed using 3 sites and 1 reagent lot. A 5-member serum panel and a 5member plasma EDTA panel were assayed in replicates of 3 with 2 runs per day, over 5 days (N = 90 for each sample).
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| Sample | Na | Mean(Index) | Within-RunRepeatability | Between-Runs | Between-Days | Between-Sites | Reproducibility | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SDb | CVc (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) | |||
| Serum A | 90 | 0.77 | 0.023 | N/A | 0.023 | N/A | 0.010 | N/A | 0.034 | N/A | 0.048 | N/A |
| Serum B | 90 | 1.07 | 0.066 | 6.1 | 0.051 | 4.7 | 0.000 | 0.0 | 0.065 | 6.0 | 0.105 | 9.8 |
| Serum C | 90 | 1.40 | 0.031 | 2.2 | 0.012 | 0.9 | 0.028 | 2.0 | 0.036 | 2.6 | 0.056 | 4.0 |
| Serum D | 90 | 4.99 | 0.103 | 2.1 | 0.119 | 2.4 | 0.077 | 1.6 | 0.255 | 5.1 | 0.310 | 6.2 |
| Serum E | 90 | 8.85 | 0.173 | 2.0 | 0.316 | 3.6 | 0.185 | 2.1 | 0.490 | 5.5 | 0.635 | 7.2 |
| Plasma,EDTA A | 90 | 0.78 | 0.025 | N/Ad | 0.001 | N/A | 0.017 | N/A | 0.032 | N/A | 0.044 | N/A |
| Plasma,EDTA B | 90 | 1.06 | 0.024 | 2.3 | 0.016 | 1.5 | 0.025 | 2.3 | 0.037 | 3.5 | 0.053 | 5.0 |
| Plasma,EDTA C | 90 | 1.39 | 0.032 | 2.3 | 0.014 | 1.0 | 0.022 | 1.6 | 0.068 | 4.9 | 0.080 | 5.7 |
| Plasma,EDTA D | 90 | 5.06 | 0.104 | 2.1 | 0.061 | 1.2 | 0.103 | 2.0 | 0.258 | 5.1 | 0.303 | 6.0 |
| Plasma,EDTA E | 90 | 8.75 | 0.824 | 9.4 | 0.093 | 1.1 | 0.148 | 1.7 | 0.404 | 4.6 | 0.934 | 10.7 |
| Control 1 | 90 | 0.36 | 0.010 | N/A | 0.009 | N/A | 0.000 | N/A | 0.017 | N/A | 0.022 | N/A |
| Control 2 | 90 | 3.31 | 0.057 | 1.7 | 0.043 | 1.3 | 0.000 | 0.0 | 0.113 | 3.4 | 0.134 | 4.0 |
³ Number of measurements
b Standard deviation
Coefficient of variation
d Not Applicable
The assay was designed to have the following reproducibility when using a 5day protocol in accordance with CLSI Document EP05-A3:
| Concentration Interval | Reproducibility |
|---|---|
| $≤$ 0.80 Index | N/Aa |
| > 0.80 Index | $≤$ 20.0% CV |
a Not applicable.
Specimen Equivalency
The specimen equivalency study was determined with the weighted Deming regression model using the ADVIA Centaur XP in accordance with CLSI document EP09c-ed3.
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This study was performed using between 97-98 sets of matched samples of three matrixes (serum separator tube (SST), EDTA plasma and lithium heparin plasma) from commercial sources.
Samples were analyzed in one replicate in randomized order using one reagent lot.
| Specimen Type | Regression Equation | Sample Interval | Na | rb |
|---|---|---|---|---|
| Plasma, EDTA | $y = 1.00x - 0.01 Index$ | 0.03-19.86 Index | 98 | 1.00 |
| Plasma, lithium heparin | $y = 0.98x - 0.01 Index$ | 0.03-17.87 Index | 97 | 0.99 |
ª Number of samples tested.
b Correlation coefficient.
The results support that EDTA Plasma and Lithium Heparin Plasma are equivalent matrixes to Serum.
Interferences
Potential interference was evaluated using the ADVIA Centaur XP system in accordance with quidance from the CLSI documents EP07-ed3 and EP-37-ed1.
Three matrixes (serum, EDTA plasma and lithium heparin plasma) have been analyzed in this study. For each sample (nonreactive, low reactive and high reactive) and each interfering substance to test, two samples (Control and Test) were analyzed.
The acceptable difference respect to the value reported for Control sample from the compounds listed below is ±10 % bias for reactive samples and ±0.10 Index for nonreactive samples.
The following substances do not interfere with the assay in the different matrixes at the concentrations indicated below:
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| Substance | Substance Test Concentration |
|---|---|
| Hemoglobin | 1000 mg/dL |
| Bilirubin, conjugated | 40 mg/dL |
| Bilirubin, unconjugated | 40 mg/dL |
| Lipemia (Intralipid) | 1500 mg/dL |
| Biotin | 3510 ng/mL |
| Cholesterol | 502 mg/dL |
| Protein (hyperproteinemic) | 15 g/dL |
| Protein (hypoproteinemic) | 3 g/dL |
Cross-reactivity
The ADVIA Centaur EBVnaG assay was evaluated for potential cross-reactivity with viral antibodies and disease state specimens using the ADVIA Centaur system.
A total of 330 samples were analyzed with ADVIA Centaur EBV-EBNA IgG on the ADVIA Centaur XP system and with an EBV EBNA IgG comparative assay.
The data are summarized in the following table:
| Clinical Category | NumberTested | ADVIA Centaur EBV-EBNA IgG Assay Results | Comparative EBV-EBNA IgGAssay Results | |||
|---|---|---|---|---|---|---|
| Nonreactive | Reactive | Negative | Equivocal | Positive | ||
| Cytomegalovirus (CMV)IgG | 10 | 5 | 5 | 5 | 0 | 5 |
| Cytomegalovirus (CMV)IgM | 10 | 9 | 1 | 9 | 0 | 1 |
| Parvovirus B19 IgG | 10 | 5 | 5 | 5 | 0 | 5 |
| Toxoplasma gondii IgG | 10 | 5 | 5 | 5 | 0 | 5 |
| Toxoplasma gondii IgM | 10 | 5 | 5 | 5 | 0 | 5 |
| Rubella IgG | 18 | 7 | 11 | 7 | 0 | 11 |
| Rubella IgM | 11 | 3 | 8 | 3 | 0 | 8 |
| Hepatitis B Virus (HBV)IgG | 11 | 6 | 5 | 6 | 0 | 5 |
| Hepatitis A Virus (HAV)IgG | 11 | 5 | 6 | 5 | 0 | 6 |
| Hepatitis C Virus (HCV)a | 11 | 5 | 6 | 4 | 1 | 6 |
| Clinical Category | NumberTested | ADVIA Centaur EBV-EBNA IgG Assay Results | Comparative EBV-EBNA IgGAssay Results | |||
| HumanImmunodeficiency Virus(HIV) | 10 | 4 | 6 | 4 | 0 | 6 |
| Herpes Simplex Virus(HSV-1) IgGb | 11 | 5 | 6 | 4 | 0 | 7 |
| Herpes Simplex Virus(HSV-2) IgGb | 12 | 4 | 8 | 3 | 0 | 9 |
| Treponema pallidum(Syphilis) | 12 | 3 | 9 | 3 | 0 | 9 |
| Varicella Zoster Virus(VZV) IgG | 10 | 6 | 4 | 6 | 0 | 4 |
| Measles virus IgG | 13 | 6 | 7 | 6 | 0 | 7 |
| Mumps virus IgG | 10 | 4 | 6 | 4 | 0 | 6 |
| Borrelia burgdorferi IgG(Lyme IgG) | 11 | 3 | 8 | 3 | 0 | 8 |
| Influenza virus IgG | 10 | 2 | 8 | 2 | 0 | 8 |
| Mycoplasma pneumoniaeIgGa | 21 | 14 | 7 | 14 | 1 | 6 |
| Antinuclear antibodies(ANA) | 10 | 9 | 1 | 9 | 0 | 1 |
| Rheumatic Factors (RF) | 12 | 3 | 9 | 3 | 0 | 9 |
| Human Anti-mouseantibodies (HAMA) | 12 | 5 | 7 | 5 | 0 | 7 |
| Human Herpes Virus(HHV6) | 14 | 10 | 4 | 10 | 0 | 4 |
| Systemic LupusErythematousus (SLE) | 10 | 7 | 3 | 7 | 0 | 3 |
| Flu vaccinated patients | 10 | 6 | 4 | 6 | 0 | 4 |
| Elevated IgG | 10 | 3 | 7 | 3 | 0 | 7 |
| Epstein Barr Virus (EBV)VCA IgM | 10 | 10 | 0 | 10 | 0 | 0 |
| Epstein Barr Virus (EBV)EBNA IgG | 10 | 9 | 1 | 9 | 0 | 1 |
| Total | 330 | 168 | 162 | 165 | 2 | 163 |
510(k) Summary
Traditional 510(k): ADVIA Centaur® EBV-EBNA IgG Page 10 of 12
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a HCV and Mycoplasma pneumoniae IgG: For each cross reactants, one sample produced equivocal outcome on comparative assay which was taken as discordant with ADVIA Centaur EBV-EBNA IgG assay. Possible cross-reactivity cannot be excluded based on these results. The results should be interpreted in the clinical context including signs, symptoms, and other laboratory information.
b HSV-1 IgG and HSV-2 IgG: For each cross reactants, one sample produced positive results by comparative assay. Possible cross-reactivity cannot be excluded based on these results. The results should be interpreted in the clinical context including signs, symptoms, and other laboratory information.
Stability 10.
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The onboard stability of the ADVIA Centaur EBV-EBNA IgG reagents is 28 days with a calibration interval of 28 days. The onboard stability of the ADVIA Centaur EBV-EBNA IgG Calibrators is 8 hours. The opened vial stability of the ADVIA Centaur EBV-EBNA IgG Calibrators is 60 days when stored at 2-8ºC. Unopened reagents and calibrators are stable until the expiration 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 EBV-EBNA IgG is substantially equivalent to the predicate device, LIAISON EBNA IgG (FDA cleared under K040120).
§ 866.3235 Epstein-Barr virus serological reagents.
(a)
Identification. Epstein-Barr virus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to Epstein-Barr virus in serum. The identification aids in the diagnosis of Epstein-Barr virus infections and provides epidemiological information on diseases caused by these viruses. Epstein-Barr viruses are thought to cause infectious mononucleosis and have been associated with Burkitt's lymphoma (a tumor of the jaw in African children and young adults) and postnasal carcinoma (cancer).(b)
Classification. Class I (general controls).