(129 days)
The BioPlex™ 2200 EBV IgG kit is a multiplex flow immunoassay intended for the qualitative detection of IgG antibodies to three (3) separate EBV antigens; Epstein-Barr Virus Nuclear Antigen-1 (EBV NA-1), Viral Capsid Antigen (EBV VCA), and Early Antigen diffuse (EBV EA-D) in human serum. The test system can be used in conjunction with the BioPlex 2200 EBV IgM kit as an aid in the laboratory diagnosis of infectious mononucleosis (IM).
The EBV IgG kit is intended for use with the Bio-Rad BioPlex 2200 System.
Assay performance characteristics have not been established for immunocompromised or immunosuppressed patients, cord blood, neonatal specimens, or infants. Assay performance characteristics have not been established for the diagnosis of nasopharyngeal carcinoma, Burkitt's lymphoma, and other EBV-associated lymphomas.
The EBV IgG kit uses multiplex flow immunoassay, a methodology that greatly resembles traditional EIA, but permits simultaneous detection and identification of many antibodies in a single tube. Three (3) different populations of beads are coated with E. coli derived recombinant proteins, EBV NA-1 (28kD and 45kD), EBV VCA p18 (40kD), and EBV EA-D (28kD) associated with infectious mononucleosis. The BioPlex 2200 System combines an aliquot of patient sample, sample diluent, and bead reagent into a reaction vessel. The mixture is incubated at 37°C. After a wash cycle, antihody, conjugated to phycoerythrin (PE), is added to the dyed beads and this mixture is incubated at 37°C. The excess conjugate is removed in another wash cycle, and the beads are re-suspended in wash buffer. The bead mixture then passes through the detector. The identity of the dyed beads is determined by the fluorescence of the dyes, and the amount of antibody captured by the antigen is determined by the fluorescence of the attached PE. Raw data is calculated in relative fluorescence intensity (RFI).
Three additional dyed beads, an Internal Standard Bead (ISB), a Serum Verification Bead (SVB) and a Reagent Blank Bead (RBB) are present in each reaction mixture to verify detector response, the addition of serum or plasma to the reaction vessel and the absence of significant non-specific binding in serum or plasma. Refer to the BioPlex 2200 System Operation Manual for more information. The instrument is calibrated using a set of seven (7) distinct calibrator vials, supplied separately by Bio-Rad Laboratories. A combination of four (4) vials representing four (4) different antibody concentrations are used for semi-quantitative calibration. The result for each of these antibodies is expressed as an antibody index (AI).
Here's a summary of the acceptance criteria and study details for the BioPlex 2200 EBV IgG Kit, Calibrators, and Controls, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria for the different performance metrics (reproducibility, precision, comparative testing). Instead, it presents the results of these studies as the "Performance Summary." Therefore, the reported performance itself serves as the basis for demonstrating the device's capabilities.
| Acceptance Criteria (Implied) | Stated Device Performance |
|---|---|
| Reproducibility (Consistency across runs, days, sites) | EBV NA-1 IgG: Total CVs for high and low positive panels ranged from 8.5% to 13.8%. Positive Control Total CV was 17.5%. EBV VCA IgG: Total CVs for high and low positive panels ranged from 8.9% to 17.8%. Positive Control Total CV was 6.9%. EBV EA-D IgG: Total CVs for high and low positive panels ranged from 8.1% to 10.9%. Positive Control Total CV was 19.2%. (Tables 19-21) |
| Precision (Consistency within Bio-Rad lab) | EBV NA-1 IgG: Total CVs for high and low positive panels ranged from 9.6% to 13.1%. Negative samples had CVs up to 14.5% (High Negative). EBV VCA IgG: Total CVs for high and low positive panels ranged from 8.7% to 13.3%. Negative samples had CVs up to 18.4% (Low Negative). EBV EA-D IgG: Total CVs for high and low positive panels ranged from 8.3% to 14.9%. Negative samples had CVs up to 30.3% (Low Negative). (Tables 22-24) |
| Comparative Performance (vs. Predicate EIA) (Agreement with established methods for serological status) | Agreement by Serological Pattern Characterization (BioPlex vs. EIA): - EBV NA-1 IgG: Overall Positive Agreement: 95.6% (95% CI: 93.2 - 97.1%). Overall Negative Agreement: 97.4% (95% CI: 94.0 - 98.9%). (Table 27) - EBV VCA IgG: Overall Positive Agreement: 96.2% (95% CI: 93.9 - 97.6%). Overall Negative Agreement: 99.4% (95% CI: 96.8 - 99.9%). (Table 29) - EBV EA-D IgG: Overall Positive Agreement: 88.1% (95% CI: 81.1 - 92.8%). Overall Negative Agreement: 84.1% (95% CI: 80.6 - 87.0%). (Table 31) |
| Serological Status Agreement (BioPlex EBV IgG & IgM vs. Predicate Assays) | Comparison of EBV Serological Status: Overall Serological Agreement: 83.3% (95% CI: 80.2 - 86.1%). Comparison of Acute and Non-acute EBV Serological Status: Overall Serological Agreement: 85.1% (95% CI: 82.1 - 87.7%). (Tables 32-33) |
| Cross-Reactivity (Minimal interference from other conditions) | The majority of samples that elicited a positive result with the BioPlex were also confirmed positive by the corresponding commercially available microplate EIA, indicating reactivity to EBV IgG antibodies rather than cross-reactivity with an interfering factor. (Table 34) |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Comparative Testing: A total of 621 banked serum samples from patients for whom an EBV test was ordered were tested. (This number reduced slightly due to analysis errors, with 618 or fewer samples used in some specific analyses).
- Data Provenance: The samples were "banked serum samples" and tested at 3 U.S. clinical testing sites. The study is retrospective, utilizing existing banked samples.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The document does not explicitly state that experts (e.g., radiologists) were used to establish ground truth for the test set. Instead, the ground truth for comparative performance and serological status was established by "corresponding commercially available microplate EIAs" and "commercially available microplate EIA and agglutination tests." The serological characterization in Table 25 (e.g., Primary Acute, Late Acute) appears to be a predefined algorithm based on results from these predicate assays.
4. Adjudication Method for the Test Set
No adjudication method by human experts is described for the test set. The interpretation of results (positive, equivocal, negative) for the BioPlex 2200 EBV IgG kit was compared directly against the results of predicate EIA assays. For percent agreement calculations, "equivocal results were assigned to the opposite clinical interpretation than that of the corresponding reference assay result" and vice versa for predicate equivocal results (Page 13).
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No MRMC comparative effectiveness study was done. This study focuses on the in-vitro diagnostic device's performance compared to predicate devices, not on human reader performance with or without AI assistance.
6. Standalone (Algorithm Only) Performance
Yes, the study primarily evaluates the standalone performance of the BioPlex 2200 EBV IgG Kit (an in-vitro diagnostic device, essentially an algorithm and assay combined) against predicate EIA assays. There is no human-in-the-loop component described for the interpretation of the BioPlex results in these performance studies; the instrument provides an antibody index (AI) which is then categorized as positive, equivocal, or negative based on predefined cutoffs (≤0.8 Al negative, 0.9 and 1.0 Al equivocal, and ≥1.1 Al positive for analytes, Page 6).
7. Type of Ground Truth Used
The ground truth used for the comparative effectiveness study was the results from "corresponding commercially available microplate EIAs" for individual analytes and "commercially available microplate EIA and agglutination tests" for comprehensive EBV serological status. This is a type of reference standard or predicate device comparison.
8. Sample Size for the Training Set
The document does not mention a distinct "training set" for an algorithm or AI model in the conventional sense. This is a 510(k) submission for an in-vitro diagnostic kit, not an AI/ML device where a separate training set would typically be described. The "expected values" section (Tables 13-18) describes the prevalence of EBV IgG antibodies in different patient populations. While these samples contribute to understanding the device's characteristics in various populations, they are presented as "expected values" rather than a formal training set for an algorithm.
9. How the Ground Truth for the Training Set Was Established
As there is no explicitly defined "training set" for an AI/ML algorithm, the concept of establishing ground truth for it does not apply directly in this document. The device's calibration involves a "set of seven (7) distinct calibrator vials" (Page 1), which are used to assign antibody index (AI) values. The specific concentrations or reference values for these calibrators are not detailed, but they would be established by the manufacturer according to internal standards and quality control processes.
{0}------------------------------------------------
KOG22//
Image /page/0/Picture/1 description: The image shows the logo for Bio-Rad Laboratories, a company that manufactures and distributes products for the life science research and clinical diagnostics markets. The logo is in white text on a black background. The text is bold and sans-serif.
BIOPLEX 2200 EBV IgG KIT, CALIBRATORS, AND CONTROLS 510(k) SUMMARY
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
DEC - 8 2005
| 510(k) Number | 510(k) Summary Report Date |
|---|---|
| K062211 | December 7, 2006 |
MANUFACTURER INFORMATION
| Manufacturer | |
|---|---|
| Manufacturer Address | Bio-Rad Laboratories, Inc.Clinical Systems Division4000 Alfred Nobel DriveHercules, CA 94547 |
| Telephone | (510) 724-7000 |
| Establishment Registration No. | 2915274 |
| Owner / Operator | Bio-Rad Laboratories, Inc.4000 Alfred Nobel DriveHercules, CA 94547 |
| Owner / Operator No. | 9929003 |
| Official Correspondent for the BioPlex 2200 EBV IgG | |
| Official Correspondent Address | Bio-Rad Laboratories6565 185th Ave NERedmond, WA 98052 |
| Telephone | 425-881-8300 |
| Establishment Registration No. | 3022521 |
| Owner / Operator | Bio-Rad Laboratories6565 185th Ave NERedmond, WA 98052 |
| Official Correspondent | Mr. Christopher Bentsen |
| Telephone | (425) 498-1709 |
| Fax | (425) 498-1651 |
CLASSIFICATION INFORMATION
| Classification Name | Epstein Barr Virus, Other (LSE) | |
|---|---|---|
| Common Name: | Multi-Analyte Detection System EBV IgG | |
| Product Trade Name | BioPlex 2200 EBV IgG Panel on the BioPlex 2200 Multi-Analyte Detection SystemBioPlex 2200 EBV IgG Control SetBioPlex 2200 EBV IgG Calibrator Set | |
| Device Class | Class I | |
| Classification Panel | Microbiology | |
| Regulation Number | 866.3235 |
{1}------------------------------------------------
Image /page/1/Picture/0 description: The image shows the logo for Bio-Rad Laboratories, a company that manufactures and distributes products for the life science research and clinical diagnostics markets. The logo is white text on a black rounded rectangle. The text is in a bold, sans-serif font.
| BioPlex2200 EBVIgG Analyte | Comparative FDA ClearedPREDICATE DEVICE | 510(k)Number | DecisionDate | |
|---|---|---|---|---|
| 1. | EBV NA-1 | Captia EBV (EBNA-1) IgG ELISA | 951549 | 4/29/96 |
| 2. | EBV VCA | Captia EBV VCA (P-18) IgG ELISA | 980912 | 3/26/98 |
| 3. | EBV EA-D | Captia EBV EAD IgG ELISA | 973123 | 7/22/98 |
LEGALLY MARKETED EQUIVALENT (SE) DEVICES
DEVICE DESCRIPTION
The EBV IgG kit uses multiplex flow immunoassay, a methodology that greatly resembles traditional EIA, but permits simultaneous detection and identification of many antibodies in a single tube. Three (3) different populations of beads are coated with E. coli derived recombinant proteins, EBV NA-1 (28kD and 45kD), EBV VCA p18 (40kD), and EBV EA-D (28kD) associated with infectious mononucleosis.12-13 The BioPlex 2200 System combines an aliquot of patient sample, sample diluent, and bead reagent into a reaction vessel. The mixture is incubated at 37°C. After a wash cycle, antihody, conjugated to phycoerythrin (PE), is added to the dyed beads and this mixture is incubated at 37°C. The excess conjugate is removed in another wash cycle, and the beads are re-suspended in wash buffer. The bead mixture then passes through the detector. The identity of the dyed beads is determined by the fluorescence of the dyes, and the amount of antibody captured by the antigen is determined by the fluorescence of the attached PE. Raw data is calculated in relative fluorescence intensity (RFI).
Three additional dyed beads, an Internal Standard Bead (ISB), a Serum Verification Bead (SVB) and a Reagent Blank Bead (RBB) are present in each reaction mixture to verify detector response, the addition of serum or plasma to the reaction vessel and the absence of significant non-specific binding in serum or plasma. Refer to the BioPlex 2200 System Operation Manual for more information. The instrument is calibrated using a set of seven (7) distinct calibrator vials, supplied separately by Bio-Rad Laboratories. A combination of four (4) vials representing four (4) different antibody concentrations are used for semi-quantitative calibration. The result for each of these antibodies is expressed as an antibody index (AI).
KIT COMPONENTS
EBV IgG Reagent Pack (Catalog No. 665-1250). The reagent pack contains supplies sufficient for 100 tests.
| Vial | Description |
|---|---|
| Bead Set | One (1) 10 mL vial, containing 3 different populations of dyed beads coatedwith affinity-purified E. coli derived recombinant proteins to EBV NA-1(28kD and 45kD), EBV VCA p18 (40kD), EBV EAD (28kD); an InternalStandard (ISB), a Serum Verification (SVB), and a Reagent Blank (RBB);with Glycerol and protein stabilizers (bovine) in a MOPS (3-[N-Morpholino]propanesulfonic acid) buffer. ProClin® 300 (0.3%) and sodium azide(<0.1%) as preservatives |
| Conjugate | One (1) 5 mL vial, containing murine monoclonal anti-humanIgG/phycoerythrin conjugate and murine anti-human FXIII / phycoerythrinconjugate, in a phosphate buffer. Proclin® 300 (0.3%) and Sodium azide(0.1%) as preservatives. |
| Sample Diluent | One (1) 10 mL vial, containing protein stabilizers (bovine and murine) in atriethanolamine buffer. Proclin® 300 (0.3%) and Sodium azide (0.1%) aspreservatives. |
{2}------------------------------------------------
Image /page/2/Picture/0 description: The image shows the logo for BIO-RAD. The logo is in white text on a black, rounded rectangle. The text is in a bold, sans-serif font.
ADDITIONAL REQUIRED ITEMS, AVAILABLE FROM BIO-RAD
| Catalog # | Description |
|---|---|
| 663-1200 | BioPlex 2200 EBV IgG Calibrator Set: Seven (7) 500 µL vials, containingantibodies to EBV VCA, EBV NA-1, and EBV EA-D, in a human serummatrix made from defibrinated plasma. Proclin® 300 (0.3%) as apreservative for all calibrators. |
| 663-1230 | BioPlex 2200 EBV IgG Control Set: Two (2) 1.5 mL vials of Positive Controlcontaining antibodies to EBV NA-1, EBV VCA, and EBV EA-D, in a humanserum matrix made from defibrinated plasma; and two (2) 1.5 mL vials ofNegative Control in a serum matrix made from defibrinated plasma.ProClin® 300 (0.3%) as a preservative for all controls. |
| 660-0817 | BioPlex 2200 System Sheath Fluid: Two (2) 4 L bottles containingPhosphate Buffered Saline (PBS). Proclin® 300 (0.3%) and Sodium azide(0.1%) as preservatives. |
| 660-0818 | BioPlex 2200 System Wash Solution: One (1) 10 L bottle containingPhosphate Buffered Saline (PBS) and Tween 20. Proclin® 300 (0.3%) andSodium azide (0.1%) as preservatives. |
| 660-0000 | BioPlex 2200 Instrument and Software. |
INTENDED USE / INDICATIONS FOR USE
BioPlex 2200 EBV IaG Kit
The BioPlex™ 2200 EBV IgG kit is a multiplex flow immunoassay intended for the qualitative detection of IgG antibodies to three (3) separate EBV antigens; Epstein-Barr Virus Nuclear Antigen-1 (EBV NA-1), Viral Capsid Antigen (EBV VCA), and Early Antigen diffuse (EBV EA-D) in human serum. The test system can be used in conjunction with the BioPlex 2200 EBV IgM kit as an aid in the laboratory diagnosis of infectious mononucleosis (IM).
The EBV IgG kit is intended for use with the Bio-Rad BioPlex 2200 System.
Assay performance characteristics have not been established for immunocompromised or immunosuppressed patients, cord blood, neonatal specimens, or infants. Assay performance characteristics have not been established for the diagnosis of nasopharyngeal carcinoma, Burkitt's lymphoma, and other EBV-associated lymphomas.
BioPlex 2200 EBV IgG Calibrator Set
The BioPlex 2200 EBV IgG Calibrator Set is intended for the calibration of the BioPlex 2200 EBV IgG Reagent Pack.
BioPlex 2200 EBV IgG Control Set
The BioPlex 2200 EBV IgG Control Set is intended for use as an assayed quality control to monitor the overall performance of the BioPlex 2200 Instrument and BioPlex 2200 EBV IgG Reagent Pack in the clinical laboratory. The performance of the BioPlex 2200 EBV IgG Control Set has not been established with any other EBV assays.
{3}------------------------------------------------
Image /page/3/Picture/0 description: The image shows the logo for Bio-Rad Laboratories, a company that manufactures and distributes products for the life science research and clinical diagnostics markets. The logo is in black and white and features the words "BIO-RAD" in a bold, sans-serif font. The logo is enclosed in a rounded rectangle. The logo is simple and recognizable.
TECHNOLOGICAL CHARACTERISTICS
The following tables summarize similarities and differences between the BioPlex 2200 EBV IgG Kit, Calibrators, and Controls and the predicate devices used in comparative studies with the BioPlex 2200 EBV IgG Kit.
A. BioPlex 2200 EBV IgG Assay: EBV NA-1
Table 1: Similarities between reagents and materials
| Similarities betweenComponents /Materials | BioPlex 2200 EBV IgG Kit | Predicate EBNA-1 IqG EIA |
|---|---|---|
| Reagents | Wash Buffer, Sample Diluent | Wash Buffer, Serum Diluent |
| Calibrator(s) | Calibrators | Calibrator |
| Controls | Negative Control and Multi-Analyte Positive Control (EBVVCA, EBV NA-1, and EBV EA-D) | Negative Control, Low PositiveControl, and High PositiveControl |
Table 2: Similarities between reagents with regard to function and use
| Similarities betweenFunction and Use | BioPlex 2200 EBV IgG Kit | Predicate EBNA-1 IgG EIA |
|---|---|---|
| Intended Use | Qualitative detection of IgGantibodies in human serum toEBNA. | Qualitative determination of IgGantibodies in human serum toEBNA. |
| Matrices | Serum | Serum |
Table 3: Differences between reagents and materials
| Differences betweenComponents /Materials | BioPlex 2200 EBV IgG Kit | Predicate EBNA-1 IgG EIA |
|---|---|---|
| Solid Phase | Bead reagent - dyed antigencoated beads | 96 well microplate - antigencoated microwells |
| Reagents | Conjugate: Anti-human IgG /Phycoerythrin | Conjugate: Anti-Human IgG /Horse-radish Peroxidase.Substrate (TMB) |
| Sheath Fluid | Sheath Fluid is used to suspendthe bead reagent and introduce itinto the detector. | Not similar; not utilized in EIA's. |
Table 4: Differences between reagents with regard to function and use
| Differences betweenFunction and Use | BioPlex 2200 EBV IgG Kit | Predicate EBNA-1 IgG EIA |
|---|---|---|
| Intended Use | Qualitative detection of IgGantibodies in human serum toEBNA. | Semi-quantitative determinationof IgG antibodies in humanserum to EBNA. |
| Analyte Detection | Multi-Analyte Detection (humanIgG antibodies to EBV VCA, EBVNA-1, and EBV EA-D) | Single Analyte Detection(human IgG antibodies to EBNA) |
{4}------------------------------------------------
Image /page/4/Picture/0 description: The image shows the logo for BIO-RAD. The text "BIO+RAD" is in white, bold, sans-serif font. The text is set against a black, rounded rectangle.
B. BioPlex 2200 EBV IgG Assay: EBV VCA
| Similarities betweenComponents /Materials | BioPlex 2200 EBV IgG Kit | Predicate EBV VCA (P-18) IgGEIA |
|---|---|---|
| Reagents | Wash Buffer, Sample Diluent | Wash Buffer, Serum Diluent |
| Calibrator(s) | Calibrators | Cut-Off Calibrator |
| Controls | Negative Control and Multi-Analyte Positive Control (EBVVCA, EBV NA-1, and EBV EA-D) | Negative Control, Low PositiveControl, and High PositiveControl |
Table 5: Similarities between reagents and materials
Table 6: Similarities between reagents with regard to function and use
| Similarities betweenFunction and Use | BioPlex 2200 EBV IgG Kit | Predicate EBV VCA (P-18) IgGEIA |
|---|---|---|
| Intended Use | Qualitative detection of IgGantibodies in human serum toEBV Viral Capsid Antigen (VCA). | Qualitative determination of IgGantibodies in human serum toEBV Viral Capsid Antigen (VCA). |
| Matrices | Serum | Serum |
Table 7: Differences between reagents and materials
| Differences betweenComponents /Materials | BioPlex 2200 EBV IgG Kit | Predicate EBV VCA (P-18) IgGEIA |
|---|---|---|
| Solid Phase | Bead reagent - dyed antigencoated beads | 96 well microplate - antigencoated microwells |
| Reagents | Conjugate: Anti-human IgG /Phycoerythrin | Conjugate: Anti-Human IgG /Horse-radish Peroxidase,Substrate (TMB) |
| Sheath Fluid | Sheath Fluid is used to suspendthe bead reagent and introduce itinto the detector. | Not similar; not utilized in EIA's. |
Table 8: Differences between reagents with regard to function and use
| Differences betweenFunction and Use | BioPlex 2200 EBV IgG Kit | Predicate EBV VCA (P-18) IgG EIA |
|---|---|---|
| Analyte Detection | Multi-Analyte Detection (humanIgG antibodies to EBV VCA, EBVNA-1, and EBV EA-D) | Single Analyte Detection(human IgG antibodies to EBVViral Capsid Antigen) |
{5}------------------------------------------------
Image /page/5/Picture/0 description: The image shows the logo for Bio-Rad Laboratories, a company that manufactures and distributes products for the life science research and clinical diagnostics markets. The logo is in black and white, with the words "BIO-RAD" in bold, sans-serif font. The logo is enclosed in a rounded rectangle.
C. BioPlex 2200 EBV IgG Assay: EBV EA-D
| Similarities betweenComponents /Materials | BioPlex 2200 EBV IgG Kit | Predicate EBV EA-D IgG EIA |
|---|---|---|
| Reagents | Wash Buffer, Sample Diluent | Wash Buffer, Serum Diluent |
| Calibrator(s) | Calibrators | Calibrator |
| Controls | Negative Control and Multi-Analyte Positive Control (EBVVCA, EBV NA-1, and EBV EA-D) | Negative Control, Low PositiveControl, and High PositiveControl |
Table 9: Similarities between reagents and materials
Table 10: Similarities between reagents with regard to function and use
| Similarities betweenFunction and Use | BioPlex 2200 EBV IgG Kit | Predicate EBV EA-D IgG EIA |
|---|---|---|
| Intended Use | Qualitative detection of IgGantibodies in human serum toEBV EA-D. | Qualitative determination of IgGantibodies in human serum toEBV EA-D. |
| Matrices | Serum | Serum |
Table 11: Differences between reagents and materials
| Differences betweenComponents /Materials | BioPlex 2200 EBV IgG Kit | Predicate EBV EA-D IgG EIA |
|---|---|---|
| Solid Phase | Bead reagent - dyed antigencoated beads | 96 well microplate - antigencoated microwells |
| Reagents | Conjugate: Anti-human IgG /Phycoerythrin | Conjugate: Anti-Human IgG /Horse-radish Peroxidase,Substrate (TMB) |
| Sheath Fluid | Sheath Fluid is used to suspendthe bead reagent and introduce itinto the detector. | Not similar; not utilized in EIA's. |
Table 12: Differences between reagents with regard to function and use
| Differences betweenFunction and Use | BioPlex 2200 EBV IgG Kit | Predicate EBV EA-D IgG EIA |
|---|---|---|
| Analyte Detection | Multi-Analyte Detection (humanIgG antibodies to EBV VCA, EBVNA-1, and EBV EA-D) | Single Analyte Detection(human IgG antibodies to EBVEA-D) |
{6}------------------------------------------------
Image /page/6/Picture/0 description: The image shows the logo for Bio-Rad. The text "BIO-RAD" is written in white, bold, sans-serif font. The text is set against a black, rounded rectangle.
PERFORMANCE SUMMARY
A. Expected Values
Expected values for the EBV IgG kit are presented by age and gender in Tables 13 - 18 for serum samples from unselected hospitalized pediatric and adult patients (N=303) and patients for which an EBV test was ordered (N=620). A total of 621 serum samples from patients for which an EBV test was ordered were tested. One (1) sample from the patients for which an EBV test was ordered population was excluded due to RBB analysis error messages during BioPlex 2200 EBV IgG testing. For all analytes, results of ≤0.8 Al are negative, 0.9 and 1.0 Al are equivocal, and ≥1.1 Al are reported as positive.
| Age | Gender | Positive | Equivocal | Negative | Total | |||
|---|---|---|---|---|---|---|---|---|
| N | % | N | % | N | % | N | ||
| < 5 years of age | F | 11 | 41% | 0 | 0% | 16 | 59% | 27 |
| < 5 years of age | M | 6 | 30% | 0 | 0% | 14 | 70% | 20 |
| 5-12 years of age | F | 13 | 59% | 0 | 0% | 9 | 41% | 22 |
| 5-12 years of age | M | 15 | 44% | 0 | 0% | 19 | 56% | 34 |
| 13-20 years of age | F | 28 | 80% | 0 | 0% | 7 | 20% | 35 |
| 13-20 years of age | M | 10 | 67% | 0 | 0% | 5 | 33% | 15 |
| 21-30 years of age | F | 5 | 83% | 0 | 0% | 1 | 17% | 6 |
| 21-30 years of age | M | 1 | 50% | 0 | 0% | 1 | 50% | 2 |
| 31-40 years of age | F | 10 | 100% | 0 | 0% | 0 | 0% | 10 |
| 31-40 years of age | M | 11 | 100% | 0 | 0% | 0 | 0% | 11 |
| 41-50 years of age | F | 13 | 100% | 0 | 0% | 0 | 0% | 13 |
| 41-50 years of age | M | 7 | 100% | 0 | 0% | 0 | 0% | 7 |
| 51-60 years of age | F | 22 | 96% | 0 | 0% | 1 | 4% | 23 |
| 51-60 years of age | M | 18 | 95% | 0 | 0% | 1 | 5% | 19 |
| 61-70 years of age | F | 11 | 100% | 0 | 0% | 0 | 0% | 11 |
| 61-70 years of age | M | 12 | 100% | 0 | 0% | 0 | 0% | 12 |
| 71-80 years of age | F | 11 | 100% | 0 | 0% | 0 | 0% | 11 |
| 71-80 years of age | M | 6 | 100% | 0 | 0% | 0 | 0% | 6 |
| 81-90 years of age | F | 11 | 100% | 0 | 0% | 0 | 0% | 11 |
| 81-90 years of age | M | 5 | 83% | 0 | 0% | 1 | 17% | 6 |
| 91-100 years of age | F | 0 | 0% | 0 | 0% | 0 | 0% | 0 |
| 91-100 years of age | M | 2 | 100% | 0 | 0% | 0 | 0% | 2 |
| Total | 228 | 75% | 0 | 0% | 75 | 25% | 303 |
Table 13: Hospitalized Patient Samples: EBV NA-1 IgG
{7}------------------------------------------------
Image /page/7/Picture/0 description: The image shows the logo for Bio-Rad Laboratories. The logo is white text on a black background. The text is in a bold, sans-serif font. The logo is enclosed in a rounded rectangle.
| Age | Gender | Positive | Equivocal | Negative | Total | |||
|---|---|---|---|---|---|---|---|---|
| N | % | N | % | N | % | N | ||
| < 5 years of age | F | 11 | 41% | 0 | 0% | 16 | 59% | 27 |
| M | 5 | 25% | 0 | 0% | 15 | 75% | 20 | |
| 5-12 years of age | F | 14 | 64% | 0 | 0% | 8 | 36% | 22 |
| M | 15 | 44% | 0 | 0% | 19 | 56% | 34 | |
| 13-20 years of age | F | 29 | 83% | 0 | 0% | 6 | 17% | 35 |
| M | 9 | 60% | 0 | 0% | 6 | 40% | 15 | |
| 21-30 years of age | F | 6 | 100% | 0 | 0% | 0 | 0% | 6 |
| M | 1 | 50% | 0 | 0% | 1 | 50% | 2 | |
| 31-40 years of age | F | 10 | 100% | 0 | 0% | 0 | 0% | 10 |
| M | 11 | 100% | 0 | 0% | 0 | 0% | 11 | |
| 41-50 years of age | F | 13 | 100% | 0 | 0% | 0 | 0% | 13 |
| M | 7 | 100% | 0 | 0% | 0 | 0% | 7 | |
| 51-60 years of age | F | 22 | 96% | 0 | 0% | 1 | 4% | 23 |
| M | 18 | 95% | 0 | 0% | 1 | 5% | 19 | |
| 61-70 years of age | F | 10 | 91% | 1 | 9% | 0 | 0% | 11 |
| M | 11 | 92% | 1 | 8% | 0 | 0% | 12 | |
| 71-80 years of age | F | 10 | 91% | 1 | 9% | 0 | 0% | 11 |
| M | 6 | 100% | 0 | 0% | 0 | 0% | 6 | |
| 81-90 years of age | F | 11 | 100% | 0 | 0% | 0 | 0% | 11 |
| M | 5 | 83% | 0 | 0% | 1 | 17% | 6 | |
| 91-100 years of age | F | 0 | 0% | 0 | 0% | 0 | 0% | 0 |
| M | 2 | 100% | 0 | 0% | 0 | 0% | 2 | |
| Total | 226 | 75% | 3 | 1% | 74 | 24% | 303 |
Table 14: Hospitalized Patient Samples: EBV VCA IgG
| Table 15: Hospitalized Patient Samples: EBV EA-D IgG | ||||||
|---|---|---|---|---|---|---|
| -- | -- | ------------------------------------------------------ | -- | -- | -- | -- |
| Age | Gender | Positive | Equivocal | Negative | Total | |||
|---|---|---|---|---|---|---|---|---|
| N | % | N | % | N | % | N | ||
| < 5 years of age | F | 2 | 7% | 0 | 0% | 25 | 93% | 27 |
| M | 1 | 5% | 1 | 5% | 18 | 90% | 20 | |
| 5-12 years of age | F | 4 | 18% | 0 | 0% | 18 | 82% | 22 |
| M | 5 | 15% | 0 | 0% | 29 | 85% | 34 | |
| 13-20 years of age | F | 9 | 26% | 2 | 6% | 24 | 69% | 35 |
| M | 3 | 20% | 3 | 20% | 9 | 60% | 15 | |
| 21-30 years of age | F | 2 | 33% | 0 | 0% | 4 | 67% | 6 |
| M | 1 | 50% | 1 | 50% | 0 | 0% | 2 | |
| 31-40 years of age | F | 4 | 40% | 2 | 20% | 4 | 40% | 10 |
| M | 6 | 55% | 0 | 0% | 5 | 45% | 11 | |
| 41-50 years of age | F | 5 | 38% | 0 | 0% | 8 | 62% | 13 |
| M | 2 | 29% | 0 | 0% | 5 | 71% | 7 | |
| 51-60 years of age | F | 8 | 35% | 5 | 22% | 10 | 43% | 23 |
| M | 10 | 53% | 1 | 5% | 8 | 42% | 19 | |
| 61-70 years of age | F | 3 | 27% | 0 | 0% | 8 | 73% | 11 |
| M | 5 | 42% | 1 | 8% | 6 | 50% | 12 | |
| 71-80 years of age | F | 4 | 36% | 2 | 18% | 5 | 45% | 11 |
| M | 1 | 17% | 0 | 0% | 5 | 83% | 6 | |
| 81-90 years of age | F | 7 | 64% | 1 | 9% | 3 | 27% | 11 |
| M | 5 | 83% | 0 | 0% | 1 | 17% | 6 | |
| 91-100 years of age | F | 0 | 0% | 0 | 0% | 0 | 0% | 0 |
| M | 1 | 50% | 0 | 0% | 1 | 50% | 2 | |
| Total | 88 | 29% | 19 | 6% | 196 | 65% | 303 |
{8}------------------------------------------------
Image /page/8/Picture/0 description: The image shows the logo for Bio-Rad. The logo is white text on a black background. The text is in a bold, sans-serif font.
| Age | Gender | Positive | Equivocal | Negative | Total | |||
|---|---|---|---|---|---|---|---|---|
| N | % | N | % | N | % | N | ||
| < 5 years of age | F | 6 | 20% | 0 | 0% | 24 | 80% | 30 |
| < 5 years of age | M | 9 | 26% | 0 | 0% | 25 | 74% | 34 |
| 5-12 years of age | F | 22 | 35% | 0 | 0% | 40 | 65% | 62 |
| 5-12 years of age | M | 24 | 39% | 0 | 0% | 38 | 61% | 62 |
| 13-20 years of age | F | 46 | 59% | 1 | 1% | 31 | 40% | 78 |
| 13-20 years of age | M | 19 | 49% | 0 | 0% | 20 | 51% | 39 |
| 21-30 years of age | F | 42 | 91% | 0 | 0% | 4 | 9% | 46 |
| 21-30 years of age | M | 25 | 76% | 0 | 0% | 8 | 24% | 33 |
| 31-40 years of age | F | 50 | 96% | 0 | 0% | 2 | 4% | 52 |
| 31-40 years of age | M | 22 | 92% | 0 | 0% | 2 | 8% | 24 |
| 41-50 years of age | F | 33 | 100% | 0 | 0% | 0 | 0% | 33 |
| 41-50 years of age | M | 30 | 97% | 0 | 0% | 1 | 3% | 31 |
| 51-60 years of age | F | 26 | 96% | 0 | 0% | 1 | 4% | 27 |
| 51-60 years of age | M | 21 | 81% | 0 | 0% | 5 | 19% | 26 |
| 61-70 years of age | F | 11 | 85% | 0 | 0% | 2 | 15% | 13 |
| 61-70 years of age | M | 19 | 90% | 0 | 0% | 2 | 10% | 21 |
| 71-80 years of age | F | 2 | 100% | 0 | 0% | 0 | 0% | 2 |
| 71-80 years of age | M | 3 | 100% | 0 | 0% | 0 | 0% | 3 |
| 81-90 years of age | F | 2 | 100% | 0 | 0% | 0 | 0% | 2 |
| 81-90 years of age | M | 2 | 100% | 0 | 0% | 0 | 0% | 2 |
| 91-100 years of age | F | 0 | 0% | 0 | 0% | 0 | 0% | 0 |
| 91-100 years of age | M | 0 | 0% | 0 | 0% | 0 | 0% | 0 |
| Total | 414 | 67% | 1 | 0% | 205 | 33% | 620 |
Table 16: Samples from Patients for which an EBV Test was Ordered: EBV NA-1 IgG
| Table 17: Samples from Patients for which an EBV Test was Ordered: EBV VCA IgG | ||||
|---|---|---|---|---|
| -- | -- | -- | -- | -------------------------------------------------------------------------------- |
| Age | Gender | Positive | Equivocal | Negative | Total | |||
|---|---|---|---|---|---|---|---|---|
| N | % | N | % | N | % | N | ||
| < 5 years of age | F | 6 | 20% | 0 | 0% | 24 | 80% | 30 |
| < 5 years of age | M | 11 | 32% | 0 | 0% | 23 | 68% | 34 |
| 5-12 years of age | F | 21 | 34% | 0 | 0% | 41 | 66% | 62 |
| 5-12 years of age | M | 28 | 45% | 0 | 0% | 34 | 55% | 62 |
| 13-20 years of age | F | 47 | 60% | 0 | 0% | 31 | 40% | 78 |
| 13-20 years of age | M | 20 | 51% | 0 | 0% | 19 | 49% | 39 |
| 21-30 years of age | F | 43 | 93% | 1 | 2% | 2 | 4% | 46 |
| 21-30 years of age | M | 26 | 79% | 0 | 0% | 7 | 21% | 33 |
| 31-40 years of age | F | 52 | 100% | 0 | 0% | 0 | 0% | 52 |
| 31-40 years of age | M | 22 | 92% | 0 | 0% | 2 | 8% | 24 |
| 41-50 years of age | F | 32 | 97% | 0 | 0% | 1 | 3% | 33 |
| 41-50 years of age | M | 31 | 100% | 0 | 0% | 0 | 0% | 31 |
| 51-60 years of age | F | 27 | 100% | 0 | 0% | 0 | 0% | 27 |
| 51-60 years of age | M | 24 | 92% | 0 | 0% | 2 | 8% | 26 |
| 61-70 years of age | F | 12 | 92% | 0 | 0% | 1 | 8% | 13 |
| 61-70 years of age | M | 18 | 86% | 0 | 0% | 3 | 14% | 21 |
| 71-80 years of age | F | 2 | 100% | 0 | 0% | 0 | 0% | 2 |
| 71-80 years of age | M | 3 | 100% | 0 | 0% | 0 | 0% | 3 |
| 81-90 years of age | F | 2 | 100% | 0 | 0% | 0 | 0% | 2 |
| 81-90 years of age | M | 1 | 50% | 0 | 0% | 1 | 50% | 2 |
| 91-100 years of age | F | 0 | 0% | 0 | 0% | 0 | 0% | 0 |
| 91-100 years of age | M | 0 | 0% | 0 | 0% | 0 | 0% | 0 |
| Total | 428 | 69% | 1 | 0% | 191 | 31% | 620 |
{9}------------------------------------------------
Image /page/9/Picture/0 description: The image shows the logo for Bio-Rad. The logo is white text on a black background. The text is in a bold, sans-serif font and is enclosed in a rounded rectangle.
| Age | Gender | Positive | Equivocal | Negative | Total | |||
|---|---|---|---|---|---|---|---|---|
| N | % | N | % | N | % | N | ||
| < 5 years of age | F | 3 | 10% | 3 | 10% | 24 | 80% | 30 |
| < 5 years of age | M | 6 | 18% | 2 | 6% | 26 | 76% | 34 |
| 5-12 years of age | F | 7 | 11% | 3 | 5% | 52 | 84% | 62 |
| 5-12 years of age | M | 6 | 10% | 4 | 6% | 52 | 84% | 62 |
| 13-20 years of age | F | 16 | 21% | 8 | 10% | 54 | 69% | 78 |
| 13-20 years of age | M | 12 | 31% | 2 | 5% | 25 | 64% | 39 |
| 21-30 years of age | F | 16 | 35% | 2 | 4% | 28 | 61% | 46 |
| 21-30 years of age | M | 9 | 27% | 3 | 9% | 21 | 64% | 33 |
| 31-40 years of age | F | 15 | 29% | 5 | 10% | 32 | 62% | 52 |
| 31-40 years of age | M | 7 | 29% | 1 | 4% | 16 | 67% | 24 |
| 41-50 years of age | F | 10 | 30% | 2 | 6% | 21 | 64% | 33 |
| 41-50 years of age | M | 4 | 13% | 1 | 3% | 26 | 84% | 31 |
| 51-60 years of age | F | 13 | 48% | 3 | 11% | 11 | 41% | 27 |
| 51-60 years of age | M | 10 | 38% | 1 | 4% | 15 | 58% | 26 |
| 61-70 years of age | F | 6 | 46% | 1 | 8% | 6 | 46% | 13 |
| 61-70 years of age | M | 5 | 24% | 3 | 14% | 13 | 62% | 21 |
| 71-80 years of age | F | 0 | 0% | 1 | 50% | 1 | 50% | 2 |
| 71-80 years of age | M | 1 | 33% | 0 | 0% | 2 | 67% | 3 |
| 81-90 years of age | F | 0 | 0% | 0 | 0% | 2 | 100% | 2 |
| 81-90 years of age | M | 1 | 50% | 0 | 0% | 1 | 50% | 2 |
| 91-100 years of age | F | 0 | 0% | 0 | 0% | 0 | 0% | 0 |
| 91-100 years of age | M | 0 | 0% | 0 | 0% | 0 | 0% | 0 |
| Total | 147 | 24% | 45 | 7% | 428 | 69% | 620 |
:
Table 18: Samples from Patients for which an EBV Test was Ordered: EBV EA-D IgG
:
{10}------------------------------------------------
Image /page/10/Picture/0 description: The image shows the logo for Bio-Rad. The text "BIO+RAD" is in white, bold, sans-serif font. The text is set against a black, rounded rectangle.
B. Reproducibility Studies
A reproducibility panel, consisting of nine (9) panel members was prepared by Bio-Rad Laboratories. Two (2) of the nine (9) panel members had high levels of EBV NA-1 and EBV VCA: two (2) of the nine (9) panel members had high levels of EBV EA-D; two (2) of the nine (9) panel members had antibody levels near the cutoff for EBV NA-1 and EBV VCA; two (2) of the nine (9) panel members had antibody levels near the cutoff for EBV EA-D. All were prepared from positive patient samples. One (1) of the nine (9) panel members was negative for all three (3) analytes contained in the BioPlex 2200 EBV IqG kit. In addition, three (3) lots of the EBV IgG Control Set [1 positive control (antibody positive) and a negative control (antibody negative)} were also tested.
Reproducibility testing was performed at each of three (3) US testing facilities on a total of three (3) lots of the EBV IgG kit, three (3) lots of the EBV IgG Calibrator Set and three (3) lots of the EBV IgG Control Set. Each testing facility evaluated reproducibility using one (1) kit lot of EBV lgG with matched calibrators and controls. The panels were provided to each of the testing sites. Each of the nine (9) panel members and positive and negative controls was tested in quadruple (x4) on each day for three (3) days at each of three (3) US testing facilities using one (1) lot of EBV IgG reagent pack, one (1) lot of EBV IgG Calibrator Set and one (1) lot of EBV IgG Control Set (4 times x 3 days x 3 sites = 36 replicates per panel member and controls). The data were analyzed for intra-assay and inter-assay reproducibility according to the principles described in the Clinical Laboratory Standards Institute guidance EP5-A2, revised November 2004 and ISO/TR 22971:2205. The standard deviation (SD) and percent coefficient of variation (%CV) were calculated. Positive results can be found in Tables 19 - 21.
| EBV NA-1 IgGPanel Members | SampleN | Grand MeanAI | Within-Run | Between-Day | Between-Run | Between-Site* | Total | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | |||
| High Positive 1 | 36 | 4.2 | 0.1 | 3.2 | 0.0 | 0.0 | 0.1 | 2.9 | 0.3 | 7.4 | 0.4 | 8.5 |
| High Positive 2 | 36 | 4.3 | 0.1 | 3.4 | 0.1 | 2.5 | 0.1 | 2.8 | 0.3 | 7.5 | 0.4 | 9.0 |
| Low Positive 1 | 36 | 1.5 | 0.1 | 4.8 | 0.0 | 0.0 | 0.1 | 5.7 | 0.2 | 11.6 | 0.2 | 13.8 |
| Low Positive 2 | 36 | 2.1 | 0.1 | 3.2 | 0.0 | 1.1 | 0.1 | 3.7 | 0.2 | 9.4 | 0.2 | 10.7 |
| Positive Control | 36 | 2.9 | 0.1 | 1.9 | 0.0 | 1.1 | 0.1 | 2.4 | 0.5 | 17.2 | 0.5 | 17.5 |
Table 19: Reproducibility; BioPlex 2200 EBV NA-1 IgG
- Between-Site variance includes between lot variance.
Table 20: Reproducibility; BioPlex 2200 EBV VCA IgG
| EBV VCA IgGPanel Members | SampleN | Grand MeanAI | Within-Run | Between-Day | Between-Run | Between-Site* | Total | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | |||
| High Positive 1 | 36 | 3.3 | 0.1 | 3.5 | 0.0 | 0.0 | 0.1 | 3.3 | 0.4 | 12.7 | 0.4 | 13.5 |
| High Positive 2 | 36 | 3.2 | 0.1 | 3.4 | 0.0 | 0.0 | 0.1 | 3.7 | 0.2 | 7.3 | 0.3 | 8.9 |
| Low Positive 1 | 36 | 1.5 | 0.1 | 5.0 | 0.0 | 0.0 | 0.1 | 5.5 | 0.2 | 16.2 | 0.3 | 17.8 |
| Low Positive 2 | 36 | 1.3 | 0.1 | 5.8 | 0.0 | 0.0 | 0.1 | 5.0 | 0.1 | 7.6 | 0.1 | 10.8 |
| Positive Control | 36 | 2.3 | 0.1 | 2.8 | 0.0 | 0.0 | 0.1 | 2.7 | 0.1 | 5.6 | 0.2 | 6.9 |
- Between-Site variance includes between lot variance.
| Table 21: Reproducibility; BioPlex 2200 EBV EA-D IgG | |||
|---|---|---|---|
| ------------------------------------------------------ | -- | -- | -- |
| EBV EA-D IgGPanel Members | SampleN | Grand MeanAI | Within-Run | Between-Day | Between-Run | Between-Site* | Total | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | |||
| High Positive 1 | 36 | 4.1 | 0.2 | 4.4 | 0.0 | 0.8 | 0.0 | 0.0 | 0.4 | 8.7 | 0.4 | 9.8 |
| High Positive 2 | 36 | 4.0 | 0.1 | 3.7 | 0.0 | 0.7 | 0.1 | 3.5 | 0.2 | 6.2 | 0.3 | 8.1 |
| Low Positive 1 | 36 | 2.3 | 0.2 | 8.8 | 0.1 | 2.8 | 0.0 | 0.0 | 0.1 | 5.7 | 0.2 | 10.9 |
| Low Positive 2 | 36 | 2.2 | 0.1 | 4.6 | 0.0 | 0.0 | 0.1 | 3.5 | 0.1 | 4.2 | 0.2 | 7.2 |
| Positive Control | 36 | 3.0 | 0.1 | 3.1 | 0.0 | 0.0 | 0.1 | 2.5 | 0.6 | 18.8 | 0.6 | 19.2 |
- Between-Site variance includes between lot variance.
{11}------------------------------------------------
Image /page/11/Picture/0 description: The image shows the logo for BIO-RAD. The logo is white text on a black rounded rectangle. The text is in a bold, sans-serif font.
C. Precision Studies
A precision panel, consisting of six (6) panel members was prepared by Bio-Rad Laboratories. Two (2) of the six (6) panel members had high levels of the antibodies contained in the BioPlex 2200 EBV IgG kit (EBV NA-1 IgG, EBV VCA IgG, and EBV EA-D IgG) and two (2) of the six (6) panel members had antibody levels near the cutoff, both prepared from positive patient samples, Two (2) of the six (6) panel members were negative (one high negative and one low negative) for both of the analytes.
Precision testing was performed at Bio-Rad Laboratories on one lot of the EBV IgG kit, one lot of the EBV IgG Calibrator Set and one lot of the EBV IgG Control Set. Each of the six (6) panel members was tested in duplicate (x2) on two (2) runs per day for ten (10) days using one (1) lot of EBV IgG kit, one (1) lot of EBV IgG Calibrator Set and one (1) lot of EBV IgG Control Set (2 times x 2 runs x 10 days = 40 replicates per panel member). The data were analyzed for intraassay and inter-assay precision according to the principles described in the Clinical Laboratory Standards Institute guidance EP5-A2, revised November 2004 and ISO/TR 22971:2205. The standard deviation (SD) and percent coefficient of variation (%CV) were calculated. Results can be found in Tables 22 - 24.
| EBV NA-1 IgGPanel Members | SampleN* | AI Mean | Within-Run | Between-Day | Between-Run | Total | ||||
|---|---|---|---|---|---|---|---|---|---|---|
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | |||
| High Positive 1 | 42 | 4.6 | 0.2 | 4.2% | 0.3 | 6.3% | 0.3 | 5.9% | 0.4 | 9.6% |
| High Positive 2 | 42 | 4.6 | 0.2 | 4.0% | 0.2 | 5.4% | 0.4 | 8.6% | 0.5 | 10.9% |
| Low Positive 1 | 42 | 1.9 | 0.1 | 5.5% | 0.0 | 0.0% | 0.2 | 11.9% | 0.2 | 13.1% |
| Low Positive 2 | 42 | 2.2 | 0.1 | 5.0% | 0.0 | 0.0% | 0.2 | 10.4% | 0.3 | 11.5% |
| High Negative | 43 | 0.7 | 0.1 | 7.1% | 0.0 | 3.8% | 0.1 | 12.1% | 0.1 | 14.5% |
| Low Negative | 44 | 0.0 | 0.0 | 0.0% | 0.0 | 0.0% | 0.0 | 0.0% | 0.0 | 0.0% |
Table 22: Precision Results; BioPlex 2200 EBV NA-1 IgG
*Additional samples were run.
Table 23: Precision Results; BioPlex 2200 EBV VCA IgG
| EBV VCA IgGPanel Members | SampleN* | AI Mean | Within-Run | Between-Day | Between-Run | Total | ||||
|---|---|---|---|---|---|---|---|---|---|---|
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | |||
| High Positive 1 | 42 | 3.5 | 0.1 | 3.9% | 0.1 | 3.9% | 0.2 | 6.8% | 0.3 | 8.7% |
| High Positive 2 | 42 | 3.4 | 0.2 | 5.0% | 0.1 | 3.7% | 0.3 | 9.1% | 0.4 | 11.0% |
| Low Positive 1 | 42 | 1.6 | 0.1 | 8.4% | 0.0 | 2.6% | 0.1 | 8.1% | 0.2 | 11.9% |
| Low Positive 2 | 42 | 1.3 | 0.1 | 7.4% | 0.1 | 4.1% | 0.1 | 10.2% | 0.2 | 13.3% |
| High Negative | 43 | 0.6 | 0.1 | 10.8% | 0.0 | 0.0% | 0.1 | 11.4% | 0.1 | 15.7% |
| Low Negative | 44 | 0.2 | 0.0 | 16.3% | 0.0 | 6.8% | 0.0 | 5.1% | 0.0 | 18.4% |
*Additional samples were run.
{12}------------------------------------------------
Image /page/12/Picture/0 description: The image shows the logo for Bio-Rad Laboratories. The logo is white text on a black, rounded rectangle. The text is in a bold, sans-serif font.
| EBV EA-D IgGPanel Members | SampleN* | AI Mean | Within-Run | Between-Day | Between-Run | Total | ||||
|---|---|---|---|---|---|---|---|---|---|---|
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | |||
| High Positive 1 | 42 | 4.3 | 0.2 | 4.6% | 0.0 | 0.0% | 0.3 | 6.9% | 0.4 | 8.3% |
| High Positive 2 | 42 | 4.2 | 0.3 | 6.0% | 0.3 | 6.3% | 0.3 | 7.2% | 0.5 | 11.2% |
| Low Positive 1 | 42 | 2.3 | 0.2 | 10.3% | 0.1 | 4.5% | 0.2 | 9.8% | 0.3 | 14.9% |
| Low Positive 2 | 42 | 2.3 | 0.2 | 7.0% | 0.2 | 6.8% | 0.2 | 9.1% | 0.3 | 13.4% |
| High Negative | 43 | 0.7 | 0.1 | 13.4% | 0.0 | 0.0% | 0.1 | 12.9% | 0.1 | 18.6% |
| Low Negative | 44 | 0.2 | 0.1 | 29.8% | 0.0 | 5.3% | 0.0 | 0.0% | 0.1 | 30.3% |
Table 24: Precision Results; BioPlex 2200 EBV EA-D IgG
*Additional samples were run.
D. Comparative Testing
Typical Antibody Response Characterization
The following table demonstrates a generally accepted algorithm for classifying patients into an EBV status via serologic profiles. EBV status can be applied to any patient based on results of standard tests. In acute IM, both EBV IgM and EBV IgG antibodies to viral capsid antigen (VCA) rise rapidly. EBV VCA IgM antibody disappears over about four weeks. Heterophile antibody, which is of the IgM class, appears only during acute infection and fades rapidly over about four weeks. EBV EA-D IgG antibody shows a transient rise during acute infection, and becomes undetectable after 3 - 6 months. EBV NA-1 IgG antibody usually appears 3 months after initial infection and typically remains for life, as well as EBV VCA IgG.
| EBV Serological Status | EBV NA-1 IgG | EBV VCA IgG | EBV EA-D IgG | EBV VCA IgM | Heterophile Antibody |
|---|---|---|---|---|---|
| Neg (-) | Pos (+) | Pos (+) | Pos (+) | Neg (-) | |
| Neg (-) | Neg (-) | Pos (+) | Pos (+) | Pos (+) | |
| Neg (-) | Pos (+) | Neg (-) | Pos (+) | Pos (+) | |
| Neg (-) | Neg (-) | Neg (-) | Pos (+) | Pos (+) | |
| Primary Acute | Neg (-) | Neg (-) | Neg (-) | Pos (+) | Neg (-) |
| Neg (-) | Neg (-) | Pos (+) | Pos (+) | Neg (-) | |
| Neg (-) | Pos (+) | Pos (+) | Pos (+) | Pos (+) | |
| Neg (-) | Pos (+) | Pos (+) | Neg (-) | Pos (+) | |
| Neg (-) | Pos (+) | Neg (-) | Pos (+) | Neg (-) | |
| Pos (+) | Pos (+) | Pos (+) | Pos (+) | Pos (+) | |
| Pos (+) | Pos (+) | Pos (+) | Pos (+) | Neg (-) | |
| Late Acute | Pos (+) | Pos (+) | Neg (-) | Pos (+) | Pos (+) |
| Pos (+) | Pos (+) | Pos (+) | Neg (-) | Neg (-) | |
| Pos (+) | Pos (+) | Neg (-) | Pos (+) | Neg (-) | |
| Recovering | Neg (-) | Pos (+) | Pos (+) | Neg (-) | Neg (-) |
| Neg (-) | Pos (+) | Neg (-) | Neg (-) | Neg (-) | |
| Previous Infection | Pos (+) | Pos (+) | Neg (-) | Neg (-) | Neg (-) |
| Susceptible | Neg (-) | Neg (-) | Neg (-) | Neg (-) | Neg (-) |
Table 25: Serological Status
Notes: For the purposes of serological characterization, equivocal results were considered negative. Any serological pattern not identified in Table 25 should be considered inconclusive.
{13}------------------------------------------------
Image /page/13/Picture/0 description: The image shows the logo for Bio-Rad Laboratories, a company that manufactures and distributes products for the life science research and clinical diagnostics markets. The logo is white text on a black background. The text is in a bold, sans-serif font.
Comparison of BioPlex 2200 EBV IgG kit and Microplate EIA
Performance of the BioPlex 2200 EBV IqG kit was tested against corresponding commercially available microplate EIAs. A total of 621 banked serum samples from patients for which an EBV test was ordered were tested at 3 U.S. clinical testing sites. The BioPlex 2200 EBV IgG kit was run in conjunction with the BioPlex 2200 EBV IgM kit to allow for a complete antibody response profile. The characterization by antibody response was not compared with clinical data regarding presence, absence or status of disease. Two (2) samples were excluded due to RBB analysis error messages during BioPlex 2200 EBV IgM testing. One (1) sample was excluded due to RBB analysis error messages during BioPlex 2200 EBV IgG testing. Using Table 25 as a guideline, results were analyzed by BioPlex 2200 EBV IgG analytes and corresponding EBV IgG reference assays according to serological characterization based on reference assay results. For the purpose of percent agreement calculations, BioPlex 2200 EBV IgG equivocal results were assigned to the opposite clinical interpretation than that of the corresponding reference assay result. Likewise, the reference IgG assay equivocal results were assigned to the opposite clinical interpretation than that of the corresponding BioPlex 2200 EBV IgG result. Results from all sites are shown and summarized in Tables 26 - 31.
| Reference EBV NA-1 IgG Interpretation | Total | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| EBVSerological Status | PositiveBioPlex 2200EBV NA-1 IgG | EquivocalBioPlex 2200EBV NA-1 IgG | NegativeBioPlex 2200EBV NA-1 IgG | |||||||
| Pos | Eqv | Neg | Pos | Eqv | Neg | Pos | Eqv | Neg | ||
| N | N | N | N | N | N | N | N | N | N | |
| Primary Acute | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 31 | 31 |
| Late Acute | 104 | 0 | 4 | 0 | 0 | 0 | 0 | 0 | 2 | 110 |
| Recovering | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 4 |
| Previous Infection | 285 | 1 | 4 | 0 | 0 | 0 | 4 | 0 | 11 | 305 |
| Susceptible | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 125 | 127 |
| Inconclusive | 20 | 0 | 9 | 0 | 0 | 0 | 0 | 0 | 12 | 41 |
| Overall | 409 | 1 | 17 | 0 | 0 | 1 | 5 | 0 | 185 | 618 |
Table 26: BioPlex 2200 EBV NA-1 IgG vs. EIA: Comparison by Serological Pattern Characterization
{14}------------------------------------------------
Image /page/14/Picture/0 description: The image shows the logo for Bio-Rad. The logo is white text on a black background. The text is in a bold, sans-serif font and is slightly rounded.
Table 27: BioPlex 2200 EBV NA-1 IgG vs. EIA: Percent Agreement & Confidence Intervals by Serological Pattern Characterization
| EBVSerological Status | Positive Agreement | 95% CI | Negative Agreement | 95% CI | ||
|---|---|---|---|---|---|---|
| Primary Acute | (0/0) | N/A* | (31/31) | 100% | 89.0 - 100% | |
| Late Acute | (104/108) | 96.3% | 90.9 - 98.6% | (2/2) | 100% | 34.2 - 100% |
| Recovering | (0/0) | N/A* | (4/4) | 100% | 51.0 - 100% | |
| Previous Infection | (285/290) | 98.3% | 96.0 - 99.3% | (11/15) | 73.3% | 48.0 - 98.1% |
| Susceptible | (0/1) | 0.0% | N/A* | (125/126) | 99.2% | 95.6 - 99.9% |
| Inconclusive | (20/29) | 69.0% | 50.8 - 82.7% | (12/12) | 100% | 75.8 - 100% |
| Overall | (409/428) | 95.6% | 93.2 - 97.1% | (185/190) | 97.4% | 94.0 - 98.9% |
*In cases where agreement resulted in a numerator of zero (0), 95% confidence interval could not be calculated; in cases where agreement resulted in (0/0) samples, percent and 95% confidence interval could not be calculated.
| EBVSerological Status | Reference EBV VCA IgG Interpretation | Total | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| PositiveBioPlex 2200EBV VCA IgG | EquivocalBioPlex 2200EBV VCA IgG | NegativeBioPlex 2200EBV VCA IgG | ||||||||
| Pos | Eqv | Neg | Pos | Eqv | Neg | Pos | Eqv | Neg | ||
| N | N | N | N | N | N | N | N | N | N | |
| Primary Acute | 4 | 0 | 3 | 0 | 0 | 1 | 0 | 0 | 23 | |
| Late Acute | 106 | 0 | 4 | 0 | 0 | 0 | 0 | 0 | 0 | 110 |
| Recovering | 4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 |
| Previous Infection | 296 | 1 | 8 | 0 | 0 | 0 | 0 | 0 | 0 | 305 |
| Susceptible | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 127 | 127 |
| Inconclusive | 16 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 24 | 41 |
| Overall | 426 | 1 | 15 | 0 | 0 | 1 | 1 | 0 | 174 | 618 |
{15}------------------------------------------------
Image /page/15/Picture/0 description: The image shows the logo for Bio-Rad Laboratories, a company that manufactures and distributes products for the life science research and clinical diagnostics markets. The logo is white text on a black background. The text is in a bold, sans-serif font.
Table 29: BioPlex 2200 EBV VCA IgG vs. EIA: Percent Agreement & Confidence Intervals by Serological Pattern Characterization
| EBVSerological Status | Positive Agreement | 95% CI | Negative Agreement | 95% CI | ||
|---|---|---|---|---|---|---|
| Primary Acute | (4/8) | 50.0% | 21.5 - 78.5% | (23/23) | 100% | 85.7 - 100% |
| Late Acute | (106/110) | 96.4% | 91.0 - 98.6% | (0/0) | N/A* | NA* |
| Recovering | (4/4) | 100% | 51.0 - 100% | (0/0) | N/A* | NA* |
| Previous Infection | (296/305) | 97.0% | 94.5 - 98.4% | (0/0) | N/A* | NA* |
| Susceptible | (0/0) | N/A* | NA* | (127/127) | 100% | 97.1 - 100% |
| Inconclusive | (16/16) | 100% | 80.6 - 100% | (24/25) | 96.0% | 80.5 - 99.3% |
| Overall | (426/443) | 96.2% | 93.9 - 97.6% | (174/175) | 99.4% | 96.8 - 99.9% |
*In cases where agreement resulted in (0/0) samples, percent and 95% confidence interval could not be calculated.
| EBVSerological Status | Reference EBV EA-D IgG Interpretation | Total | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| PositiveBioPlex 2200EBV EA-D IgG | EquivocalBioPlex 2200EBV EA-D IgG | NegativeBioPlex 2200EBV EA-D IgG | ||||||||
| Pos | Eqv | Neg | Pos | Eqv | Neg | Pos | Eqv | Neg | ||
| N | N | N | N | N | N | N | N | N | N | |
| Primary Acute | 18 | 1 | 2 | 0 | 0 | 0 | 2 | 1 | 7 | 31 |
| Late Acute | 72 | 1 | 3 | 4 | 0 | 0 | 6 | 3 | 21 | 110 |
| Recovering | 4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 |
| Previous Infection | 0 | 0 | 0 | 5 | 3 | 3 | 23 | 22 | 249 | 305 |
| Susceptible | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 9 | 116 | 127 |
| Inconclusive | 10 | 2 | 1 | 0 | 0 | 0 | 2 | 2 | 24 | 41 |
| Overall | 104 | 4 | 6 | 9 | 4 | 4 | 33 | 37 | 417 | 618 |
Table 30: BioPlex 2200 EBV EA-D IgG vs. EIA: Comparison by Serological Pattern Characterization
{16}------------------------------------------------
Image /page/16/Picture/0 description: The image shows the logo for BIO-RAD. The logo is white text on a black background. The text is in all capital letters and has a plus sign between BIO and RAD. The logo is inside of a rounded rectangle.
Table 31: BioPlex 2200 EBV EA-D IgG vs. EIA: Percent Agreement & Confidence Intervals by Serological Pattern Characterization
| EBVSerological Status | Positive Agreement | 95% CI | Negative Agreement | 95% CI | ||
|---|---|---|---|---|---|---|
| Primary Acute | (18/21) | 85.7% | 65.4 - 95.0% | (7/10) | 70.0% | 39.7 - 89.2% |
| Late Acute | (72/76) | 94.7% | 87.2 - 97.9% | (21/34) | 61.8% | 45.0 - 76.1% |
| Recovering | (4/4) | 100% | 51.0 - 100% | (0/0) | N/A* | N/A* |
| Previous Infection | (0/3) | 0.0% | N/A* | (249/299) | 83.3% | 78.6 - 87.1% |
| Susceptible | (0/1) | 0.0% | N/A* | (116/125) | 92.8% | 86.9 - 96.2% |
| Inconclusive | (10/13) | 76.9% | 49.7 - 91.8% | (24/28) | 85.7% | 68.5 - 94.3% |
| Overall | (104/118) | 88.1% | 81.1 - 92.8% | (417/496) | 84.1% | 80.6 - 87.0% |
*In cases where agreement resulted in a numerator of zero (0), 95% confidence interval could not be calculated; in cases where agreement resulted in (0/0) samples, percent agreement and 95% confidence interval could not be calculated.
Comparison of Characterization EBV Serological Status
Using Table 25 as a guideline, samples characterized into serological status associated with EBV disease, using the commercially available microplate EIA and agglutination tests, were compared with characterizations using BioPlex 2200 EBV IgG and IgM kits. The EBV IgG kit was run in conjunction with the EBV IgM kit to allow for a complete antibody response profile. The characterization by antibody response was not compared with clinical data regarding presence, absence or status of disease. Results from 618 serum samples tested at 3 U.S. clinical testing sites are shown in Table 32.
| EBV Serological status | BioPlex 2200 EBV IgG & IgM Profile | Total | % Serological Agreement | 95% Confidence Interval | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Primary Acute | Late Acute | Recovering | Previous Infection | Susceptible | Inconclusive | |||||
| Commercially Available Assays | Primary Acute | 30 | 0 | 0 | 0 | 0 | 1 | 31 | 96.8% | 83.8 - 99.4% |
| Late Acute | 5 | 90 | 1 | 13 | 0 | 1 | 110 | 81.8% | 73.6 - 87.9% | |
| Recovering | 1 | 0 | 3 | 0 | 0 | 0 | 4 | 75.0% | 30.0 - 95.4% | |
| Previous Infection | 0 | 31 | 2 | 263 | 4 | 5 | 305 | 86.2% | 81.9 - 89.7% | |
| Susceptible | 4 | 0 | 0 | 0 | 122 | 1 | 127 | 96.1% | 91.1 - 98.3% | |
| Inconclusive | 6 | 10 | 0 | 7 | 11 | 7 | 41 | 17.1% | 8.5 - 31.3% | |
| Overall | 46 | 131 | 6 | 283 | 137 | 15 | 618 | 83.3% | 80.2 - 86.1% |
Table 32: Comparison of EBV Serological Status
Note: Calculations are performed for unshaded areas only.
{17}------------------------------------------------
Image /page/17/Picture/0 description: The image contains the logo for BIO-RAD. The logo is white text on a black background. The text is bold and sans-serif.
Comparison of Acute and Non-acute EBV Serological Status
The results obtained from the summarized information provided in Table 32 were further classified into two groups; Acute Infection and Non-Acute Infection. Acute Infection includes Primary Acute and Late Acute. Non-Acute Infection includes samples characterized as Susceptible, Recovering and Previous Infection as defined in Table 25. Inconclusive includes any samples whose patterns of antibody reactivity are not consistent with any category listed in Table 25. Results are summarized in Table 33.
| CommerciallyAvailable Assays | EBV Serological status | Acute | Non-Acute | Inconclusive | Total | % SerologicalAgreement | 95% ConfidenceInterval |
|---|---|---|---|---|---|---|---|
| Acute | 125 | 14 | 2 | 141 | 88.7% | ||
| Non-Acute | 36 | 394 | 6 | 436 | 90.4% | 87.2 - 92.8% | |
| Inconclusive | 16 | 18 | 7 | 41 | 17.1% | 8.5 - 31.3% | |
| Overall | 177 | 426 | 15 | 618 | 85.1% | 82.1 - 87.7% |
Note: Calculations are performed for unshaded areas only.
{18}------------------------------------------------
Image /page/18/Picture/0 description: The image shows the logo for Bio-Rad. The text "BIO-RAD" is in white, bold, sans-serif font. The text is set against a black background, which is in the shape of a rounded rectangle.
E. Cross-Reactivity
A cross-reactivity study was performed to determine if samples from various disease states and other potentially interfering factors interfere with test results when tested with the BioPlex 2200 EBV IgG kit. A panel of ten (10) specimens* positive for each cross reactant were evaluated for possible cross reactivity with the BioPlex 2200 EBV IgG kit for each of the three EBV IgG antibody assays. Due to the high prevalence of EBV IgG antibodies in the normal population, the test specimens were also evaluated on corresponding commercially available microplate EIAs. Most of the samples evaluated were high positive for each disease state. The majority of all samples that did elicit a positive result were also confirmed positive by the corresponding commercially available microplate EIA, indicating reactivity to EBV IgG antibodies rather than cross reactivity with a potentially interfering factor. Results can be found in Table 34.
*Due to limited availability of samples, only four E. coli specimens were evaluated.
{19}------------------------------------------------
Image /page/19/Picture/0 description: The image shows the logo for Bio-Rad Laboratories, a company that manufactures and distributes products for the life science research and clinical diagnostics markets. The logo is a black rectangle with rounded corners, and the words "BIO-RAD" are written in white letters inside the rectangle. The letters are bold and sans-serif, and the "+" symbol is used in place of the hyphen.
Table 34: Cross Reactivity
| Cross Reactives | N | Method | BioPlex 2200 EBV IgG | ||
|---|---|---|---|---|---|
| EBV NA-1 IgG | EBV VCA IgG | EBV EA-D IgG | |||
| ANA | 10 | BioPlex 2200 | 9 | 10 | 7 |
| EIA | 9 | 10 | 7 | ||
| Discrepants | 0 | 0 | 0 | ||
| Rheumatoid Factor | 10 | BioPlex 2200 | 10 | 10 | 1 |
| EIA | 10 | 10 | 1* | ||
| Discrepants | 0 | 0 | 0 | ||
| Toxo IgG | 10 | BioPlex 2200 | 9 | 9 | 2 |
| EIA | 9 | 9* | 2* | ||
| Discrepants | 0 | 0 | 0 | ||
| Rubella IgG | 10 | BioPlex 2200 | 10 | 10 | 2 |
| EIA | 10 | 10 | 1* | ||
| Discrepants | 0 | 0 | 1 | ||
| CMV IgG | 10 | BioPlex 2200 | 10 | 10 | 2 |
| EIA | 10 | 10 | 2** | ||
| Discrepants | 0 | 0 | 1 | ||
| VZV IgG | 10 | BioPlex 2200 | 8 | 8 | 1 |
| EIA | 9 | 8 | 1 | ||
| Discrepants | 1 | 0 | 0 | ||
| HSV-1 IgG | 10 | BioPlex 2200 | 10 | 10 | 2 |
| EIA | 10 | 10 | 3 | ||
| Discrepants | 0 | 0 | 1 | ||
| HSV-2 IgG | 10 | BioPlex 2200 | 10 | 10 | 3 |
| EIA | 10 | 10 | 4 | ||
| Discrepants | 0 | 0 | 1 | ||
| HIV | 10 | BioPlex 2200 | 10 | 9 | 1 |
| EIA | 10 | 10 | 2** | ||
| Discrepants | 0 | 1 | 1 | ||
| E. coli | 4 | BioPlex 2200 | 4 | 4 | 0 |
| EIA | 4 | 4 | 0* | ||
| Discrepants | 0 | 0 | 0 | ||
| Pregnant women | 10 | BioPlex 2200 | 9 | 9 | 3 |
| EIA | 9 | 10 | 3* | ||
| Discrepants | 0 | 1 | 0 |
*One Equivocal Sample; **Two Equivocal Samples
{20}------------------------------------------------
Image /page/20/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with three stripes forming its body and wing. The eagle is facing to the right. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES, USA" is arranged in a circular fashion around the eagle.
Public Health Service
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Mr. David Bhend Regulatory Affairs Associate Bio-Rad Laboratories, Inc. Diagnostics Group 6565 185th Ave, N.E. Redmond, WA 98052
DEC - 8 2006
Re: K062211
Trade/Device Name: BioPlex 2200 EBV IgG Panel on the BioPlex 2200 Multi-Analyte Detection System BioPlex 2200 EBV IgG Control Set BioPlex 2200 EBV IgG Calibrator Set Regulation Number: 21 CFR 866.3235 Regulation Name: Epstein-Barr virus serological reagents Regulatory Class: Class I Product Code: LSE Dated: November 13, 2006 Received: November 14, 2006
Dear Mr. Bhend:
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. 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.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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 requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
{21}------------------------------------------------
This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0484. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (240) 276-3150, or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.
Sincerely yours,
face, am
Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
{22}------------------------------------------------
INDICATIONS FOR USE STATEMENT
510(k) Number: K062211
BioPlex 2200 EBV IgG Kit on the BioPlex 2200 Multi-Analyte Device Name: Detection System BioPlex 2200 EBV IqG Control Set BioPlex 2200 EBV IgG Calibrator Set
Indications for Use:
BioPlex 2200 EBV laG Kit
The BioPlex™ 2200 EBV IgG kit is a multiplex flow immunoassay intended for the qualitative detection of IgG antibodies to three (3) separate EBV antigens; Epstein-Barr Virus Nuclear Antigen-1 (EBV NA-1), Viral Capsid Antigen (EBV VCA), and Early Antigen diffuse (EBV EA-D) in human serum. The test system can be used in conjunction with the BioPlex 2200 EBV IgM kit as an aid in the laboratory diagnosis of infectious mononucleosis (IM).
The EBV IgG kit is intended for use with the Bio-Rad BioPlex 2200 System.
Assay performance characteristics have not been established for immunocompromised or immunosuppressed patients, cord blood, neonatal specimens, or infants. Assay performance characteristics have not been established for the diagnosis of nasopharyngeal carcinoma, Burkit's lymphoma, and other EBV-associated lymphomas.
BioPlex 2200 EBV IqG Calibrator Set
The BioPlex 2200 EBV IgG Calibrator Set is intended for the calibration of the BioPlex 2200 EBV IgG Reagent Pack.
BioPlex 2200 EBV IgG Control Set
The BioPlex 2200 EBV IgG Control Set is intended for use as an assayed quality control to monitor the overall performance of the BioPlex 2200 Instrument and BioPlex 2200 EBV IqG Reagent Pack in the clinical laboratory. The performance of the BioPlex 2200 EBV IgG Control Set has not been established with any other EBV assays.
Prescription Use: × ______________________________________________________________________________________________________________________________________________________________________________ (Per 21 CFR 801.109)
AND/OR
Over-The-Counter Use: (Optional Format 1-2-96)
(PLEASE DO NOT WRITE BELOW THIS LINE – CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
510(k)________________________________________________________________________________________________________________________________________________________________________
§ 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).