(272 days)
Not Found
No
The summary describes a standard in vitro diagnostic immunoassay for detecting antibodies. There is no mention of AI, ML, image processing, or any other technology typically associated with AI/ML in medical devices. The performance studies and metrics are standard for this type of assay.
No
The device is an in vitro diagnostic (IVD) assay designed to detect antibodies to Epstein-Barr virus (EBV) for diagnostic purposes, not to provide therapy.
Yes
The "Intended Use / Indications for Use" section explicitly states that the assay is for "in vitro diagnostic use" and "is intended for use as an aid in the diagnosis of Epstein-Barr virus infection, such as infectious mononucleosis."
No
The device is an in vitro diagnostic assay that uses the ADVIA Centaur XP system, which is a hardware platform. The summary describes performance studies related to the assay's interaction with biological samples and the system, indicating it is not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
The "Intended Use / Indications for Use" section explicitly states: "The ADVIA Centaur EBV-EBNA IgG (EBVnaG) assay is for in vitro diagnostic use..." This directly identifies the device as an IVD.
N/A
Intended Use / Indications for Use
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.
Product codes (comma separated list FDA assigned to the subject device)
LLM, LSE
Device Description
Not Found
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
pediatric (2-21 years old) and adult
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
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.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
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.
- Population 1:
- NPA = 92.8% (323/348); 95% CI: 89.6% - 95.1%
- PPA = 99.4% (1074/1080); 95% CI: 98.8% - 99.7%
- Population 2:
- NPA = 98.2% (164/167); 95% CI: 94.9% - 99.4%
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.
- Pediatric Population 1:
- NPA = 97.3% (220/226); 95% CI: 94.3% - 98.8%
- PPA = 98.4% (249/253); 95% CI: 96.0% - 99.4%
- Pediatric Population 2:
- NPA = 100% (72/72); 95% CI: 94.9% - 100%
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.
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).
The assay was designed to have the following reproducibility when using a 5day protocol in accordance with CLSI Document EP05-A3:
Concentration Interval:
- ≤ 0.80 Index: N/A
-
0.80 Index: ≤ 20.0% CV
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. 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.
- Plasma, EDTA: y = 1.00x - 0.01 Index, Sample Interval: 0.03-19.86 Index, N=98, r=1.00
- Plasma, lithium heparin: y = 0.98x - 0.01 Index, Sample Interval: 0.03-17.87 Index, N=97, r=0.99
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.
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.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
- Total Study Population:
- Negative percent agreement (NPA) = 92.8% (95% CI: 89.6% - 95.1%) for Population 1 (323/348)
- Positive percent agreement (PPA) = 99.4% (95% CI: 98.8% - 99.7%) for Population 1 (1074/1080)
- NPA = 98.2% (95% CI: 94.9% - 99.4%) for Population 2 (164/167)
- Pediatric Population:
- NPA = 97.3% (95% CI: 94.3% - 98.8%) for Pediatric Population 1 (220/226)
- PPA = 98.4% (95% CI: 96.0% - 99.4%) for Pediatric Population 1 (249/253)
- NPA = 100% (95% CI: 94.9% - 100%) for Pediatric Population 2 (72/72)
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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).
0
August 07, 2024
Image /page/0/Picture/1 description: The image shows 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 the FDA logo, which 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.
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).
1
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
2
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)
CONTINUE ON A SEPARATE PAGE IF NEEDED.
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3
Image /page/3/Picture/0 description: The image shows the word "werfen" in a bold, sans-serif font. The color of the text is a dark blue. The letters are evenly spaced and the word is horizontally oriented.
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.
Av. Can Montcau, 7
Lliçà d'Amunt 08186
Barcelona (Spain) |
| ------------------------------- | -------------------------------------------------------------------------------- |
|---|
| 2. Contact Person | Dominique Monferrer, Regulatory Affairs Director
Phone: +34 93 860 90 00
Email: dmonferrer@werfen.com |
| ------------------- | ------------------------------------------------------------------------------------------------------------- |
|---|
| 3. Preparation Date | 2023-Nov-09 |
|---|---|
| --------------------- | ------------- |
| 4. Device Trade
| Name | 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) |
|---|---|
| --------------------- | ---------------------------- |
4
we
| 7. Indications for
Use / Intended
Use | The ADVIA Centaur EBV-EBNA IgG (EBVna
assay is for in vitro diagnostic use in th
qualitative detection of IgG antibodies to Epstei
Barr virus (EBV) nuclear antigen (EBNA)
human pediatric (2-21 years old) and adu
serum and plasma (EDTA and lithium hepari
using the ADVIA Centaur XP system. When use
in conjunction with other EBV markers, this assa
is intended for use as an aid in the diagnosis of
Epstein-Barr virus infection, such as infectiou
mononucleosis |
| ------------------------------------------------------ | ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- |
|---|
5
we
| COMPARISON PREDICATE | ||
|---|---|---|
| Item | Predicate | New Device |
| Trade Names | LIAISON EBNA IgG | ADVIA Centaur EBV-EBNA |
| IgG | ||
| 510K no. | K040120 | K233605 |
| Manufacturer | DiaSorin, S.p.A. | |
| Via Crescentino, snc | ||
| 13040 Saluggia (Vercelli) Italy | Siemens Healthcare | |
| Diagnostics Inc. | ||
| 511 Benedict Avenue, | ||
| Tarrytown, NY 10591 USA | ||
| Intended use | The LIAISON EBNA IgG assay | |
| uses chemiluminescent | ||
| immunoassay (CLIA) | ||
| technology on the LIAISON | ||
| Analyzer family* for the | ||
| qualitative determination of | ||
| specific IgG antibodies to | ||
| Epstein-Barr virus (EBV) | ||
| nuclear antigen synthetic | ||
| peptide (EBNA-1) in human | ||
| serum. When performed in | ||
| conjunction with other EBV | ||
| markers, this assay can be | ||
| used as an aid in the clinical | ||
| laboratory diagnosis of Epstein- | ||
| Barr Viral Syndrome in patients | ||
| with signs and symptoms of | ||
| EBV infection such as infectious | ||
| mononucleosis. | ||
| *(LIAISON and LIAISON XL) | The ADVIA Centaur EBV- | |
| EBNA IgG assay is for in | ||
| vitro diagnostic use in the | ||
| qualitative detection of IgG | ||
| 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. | ||
| Similarities | ||
| Measurand | Specific IgG antibodies to | |
| Epstein-Barr virus (EBV) | ||
| nuclear antigen synthetic | ||
| peptide (EBNA-1). | To detect IgG antibodies to | |
| the Epstein-Barr virus (EBV) | ||
| nuclear antigen (EBNA). | ||
| Regulation | ||
| Section | 21 CFR 866.3235 | Same |
6
| Product Code | LLM, LSE | Same |
|---|---|---|
| Classification | Class I (general controls) | Same |
| Assay Type | Qualitative | Same |
| Technology | Chemiluminescent | |
| immunoassay (CLIA) | Same | |
| Antigen | EBNA-1 | Same |
| Differences | ||
| Sample type | Human serum | Human serum and plasma |
| (EDTA and lithium heparin) | ||
| Target | ||
| Population | 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:
7
| Population 1 | ||||
|---|---|---|---|---|
| ADVIA Centaur | ||||
| EBVnaG 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 Centaur | ||||
| EBVnaG 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.
8
| Population 1 | ||||
|---|---|---|---|---|
| ADVIA Centaur | ||||
| EBVnaG 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 Centaur | ||||
| EBVnaG 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:
9
| 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
(%) |
| Serum
A | 0.69 | 0.015 | 2.1 | 0.026 | 3.8 | 0.000 | 0.0 | 0.006 | 0.9 | 0.030 | 4.4 |
| Serum
B | 1.01 | 0.019 | 1.8 | 0.029 | 2.8 | 0.000 | 0.0 | 0.092 | 9.0 | 0.098 | 9.7 |
| Serum
C | 1.34 | 0.024 | 1.8 | 0.029 | 2.2 | 0.047 | 3.5 | 0.167 | 12.5 | 0.178 | 13.3 |
| Serum
D | 4.98 | 0.074 | 1.5 | 0.084 | 1.7 | 0.166 | 3.3 | 0.326 | 6.5 | 0.382 | 7.7 |
| Serum
E | 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 |
| Control
1 | 0.32 | 0.007 | N/Ac | 0.007 | N/A | 0.009 | N/A | 0.006 | N/A | 0.014 | N/A |
| Control
2 | 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).
10
| Sample | Na | Mean
(Index) | Within-Run
Repeatability | | 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 | Number
Tested | ADVIA Centaur EBV-
EBNA IgG Assay Results | | Comparative EBV-EBNA IgG
Assay 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 | Number
Tested | ADVIA Centaur EBV-
EBNA IgG Assay Results | | Comparative EBV-EBNA IgG
Assay Results | | |
| Human
Immunodeficiency 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 pneumoniae
IgGa | 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-mouse
antibodies (HAMA) | 12 | 5 | 7 | 5 | 0 | 7 |
| Human Herpes Virus
(HHV6) | 14 | 10 | 4 | 10 | 0 | 4 |
| Systemic Lupus
Erythematousus (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).