K Number
K073382
Date Cleared
2008-07-28

(238 days)

Product Code
Regulation Number
866.3235
Reference & Predicate Devices
N/A
Predicate For
N/A
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

Focus Diagnostics' Plexus™ EBV IgG Multi-Analyte Diagnostics test kit is intended for qualitatively detecting the presence or absence of human IgG class antibodies to viral capsid antigen (VCA), early antigen- diffuse (EA-D), and nuclear antigen (EBNA-1) of Epstein-Barr virus in human sera. The test is indicated as an aid in the diagnosis of EBV infection and EBV-associated infectious mononucleosis.

The performance of this assay has not been established for use in the diagnosis of nasopharyngeal carcinoma and Burkit's lymphoma, for testing of immunocompromised patients, for use by a point of care facility or for use with automated equipment. This assay has not been evaluated for donor screening.

Device Description

Multiplexed Immunoassay for the Qualitative Detection of Human IgG Antibodies to Epstein-Barr Virus

The Focus Diagnostics Plexus™ EBV IgG uses an Antigen Bead suspension that contains three distinct EBV antigen bead types (EA-D, VCA, & EBNA-1) and one process control bead type that fluoresce at different wavelengths and/or intensities.

The Focus Diagnostics Plexus™ EBV IgG is a three step procedure,

  • Patient sera are diluted, and the diluted sera are incubated with Antigen Beads. If EBV antibodies are present, then the antibodies bind to the corresponding antigen beads.
  • Phycoerythrin-conjugated goat Anti-human IgG (Conjugate) is added, binds to the bound EBV antibody (if present), and forms a Conjugate-EBV antibody-antigen bead sandwich.
  • Fluorescence from each distinct EBV antigen bead type is measured and compared against a Cutoff Calibrator.
AI/ML Overview

Here's an analysis of the provided text regarding the acceptance criteria and study for the Plexus EBV IgG Multi-Analyte Diagnostics device:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria in terms of specific percentages for agreement. Instead, it presents the "Positive Percent Agreement" for different serological statuses when compared against predicate devices. While not an explicit acceptance criterion, the percentage agreement values indicate the device's performance relative to the established ground truth.

Performance MetricAcceptance Criteria (Implicit from Study Design)Reported Device Performance (vs. Predicate)
EBV VCA IgG (Prospective)High positive percent agreement across serological statuses
Primary Acute (Positive)N/A (implied high agreement)100% (57/57), 95% CI: 93.7-100%
Late Acute (Positive)N/A (implied high agreement)97.2% (70/72), 95% CI: 90.4-99.2%
Recovering (Positive)N/A (implied high agreement)100% (1/1), 95% CI: 20.7-100%
Previous Infection (Positive)N/A (implied high agreement)96.6% (282/292), 95% CI: 93.8-98.1%
No Infection (Negative)N/A (implied high agreement)93.5% (203/217), 95% CI: 89.5-96.1%
Indeterminate (Positive)N/A (implied high agreement)98% (49/50), 95% CI: 89.5-99.6%
Indeterminate (Negative)N/A (implied high agreement)100% (15/15), 95% CI: 79.6-100%
EBV VCA IgG (Retrospective)High positive percent agreement across serological statuses
Acute (Positive)N/A (implied high agreement)93.4% (99/106), 95% CI: 87-96.8%
Acute (Positive, second entry)N/A (implied high agreement)100% (8/8), 95% CI: 67.6-100%
No Infection (Positive)N/A (implied high agreement)100% (1/1), 95% CI: 20.7-100%
Indeterminate (Positive)N/A (implied high agreement)93.9% (31/33), 95% CI: 80.4-98.3%
EBV EBNA-1 IgG (Prospective)High positive percent agreement across serological statuses
Acute (Negative)N/A (implied high agreement)100% (60/60), 95% CI: 94-100%
Late Acute (Positive)N/A (implied high agreement)94.2% (65/69), 95% CI: 86-97.7%
Late Acute (Negative)N/A (implied high agreement)100% (3/3), 95% CI: 43.8-100%
Recovering (Negative)N/A (implied high agreement)100% (1/1), 95% CI: 20.7-100%
Previous Infection (Positive)N/A (implied high agreement)93.7% (266/284), 95% CI: 90.2-96%
Previous Infection (Negative)N/A (implied high agreement)92.9% (13/14), 95% CI: 68.5-98.7%
No Infection (Negative)N/A (implied high agreement)99.6% (226/227), 95% CI: 97.5-99.9%
Indeterminate (Positive)N/A (implied high agreement)76.3% (29/38), 95% CI: 60.8-87%
Indeterminate (Negative)N/A (implied high agreement)100% (27/27), 95% CI: 87.5-100%
EBV EBNA-1 IgG (Retrospective)High positive percent agreement across serological statuses
Primary Acute (Negative)N/A (implied high agreement)99.1% (105/106), 95% CI: 94.8-99.8%
Late Acute (Negative)N/A (implied high agreement)100% (4/4), 95% CI: 51-100%
No Infection (Negative)N/A (implied high agreement)100% (2/2), 95% CI: 34.2-100%
Indeterminate (Negative)N/A (implied high agreement)100% (26/26), 95% CI: 87.1-100%
EBV EA-D IgG (Prospective)High positive percent agreement across serological statuses
Primary Acute (Positive)N/A (implied high agreement)93% (40/43), 95% CI: 81.4-97.6%
Primary Acute (Negative)N/A (implied high agreement)76.5% (13/17), 95% CI: 52.7-90.4%
Late Acute (Positive)N/A (implied high agreement)80.4% (41/51), 95% CI: 67.5-89%
Late Acute (Negative)N/A (implied high agreement)81% (17/21), 95% CI: 60-92.3%
Recovering (Positive)N/A (implied high agreement)0% (0/1), 95% CI: 0-79.3% (Note: This single sample result is concerning)
Previous Infection (Negative)N/A (implied high agreement)96% (286/298), 95% CI: 93.1-97.7%
No Infection (Negative)N/A (implied high agreement)98.2% (223/227), 95% CI: 95.6-99.3%
Indeterminate (Positive)N/A (implied high agreement)26.9% (7/26), 95% CI: 13.7-46.1%
Indeterminate (Equivocal)N/A (implied high agreement)6.3% (2/32), 95% CI: 1.7-20.1%
Indeterminate (Negative)N/A (implied high agreement)62.2% (23/37), 95% CI: 46.1-75.9%
EBV EA-D IgG (Retrospective)High positive percent agreement across serological statuses
Primary Acute (Positive)N/A (implied high agreement)93.4% (57/61), 95% CI: 84.3-97.4%
Primary Acute (Negative)N/A (implied high agreement)77.8% (35/45), 95% CI: 63.7-87.5%
Late Acute (Positive)N/A (implied high agreement)100% (3/3), 95% CI: 43.8-100%
Late Acute (Negative)N/A (implied high agreement)80% (4/5), 95% CI: 37.6-96.4%
No Infection (Negative)N/A (implied high agreement)100% (2/2), 95% CI: 34.2-100%
Indeterminate (Positive)N/A (implied high agreement)66.7% (8/12), 95% CI: 39.1-86.2%
Indeterminate (Equivocal)N/A (implied high agreement)0% (0/14), 95% CI: 0-21.5%
Indeterminate (Negative)N/A (implied high agreement)40.9% (9/22), 95% CI: 23.3-61.3%

2. Sample Size Used for the Test Set and Data Provenance

  • Total Sample Size (Test Set): 873 samples
    • Prospective Samples: 723 samples (sequentially submitted for routine EBV testing, masked).
    • Retrospective Samples: 150 samples (pre-selected based on EBV VCA concentrations from a FDA-cleared device, likely to be cases with presumed acute infection).
  • Data Provenance: United States
    • Samples were collected at three sites:
      • A hospital laboratory located in the Northeast (USA)
      • A pediatric hospital laboratory located in the Mid-West (USA)
      • Focus Diagnostics (manufacturer's site)

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

The document does not mention the use of "experts" in the traditional sense (e.g., radiologists, pathologists) to establish ground truth for the test set.

Instead, the ground truth was established by comparison to commercially available, FDA-cleared predicate devices and an algorithm based on serological profiles.

  • For VCA IgG, the ground truth was a "consensus predicate" derived from a combination of:
    • FDA-cleared commercially available ELISA
    • FDA-cleared commercially available immunofluorescent (IFA) test
    • FDA-cleared commercially available flow cytometry-based immunoassay
  • For EBNA-1 IgG and EA-D IgG, the ground truth was a single commercially available ELISA test.
  • Additionally, the "Serological status was determined by the use of commercially available ELISA assays for the EBV analytes EBNA-1 IgG, VCA IgG and VCA IgM and a commercially available heterophile rapid test for the Heterophile antibody." This indicates a comprehensive panel of existing diagnostic tests was used to define the overall EBV serological status that the Plexus device was compared against.

4. Adjudication Method for the Test Set

  • For Plexus EBV VCA IgG vs. Consensus Predicate: A consensus-based algorithm (2/3 majority rule) was used to determine the predicate result for comparison with the Plexus VCA IgG result. This means that out of the three predicate devices, at least two had to agree on the classification (positive/negative) for a sample to have a definitive "consensus predicate" result. If a 2/3 majority could not be obtained, the sample was reported as "No consensus."
  • For Plexus EBV EBNA-1 IgG and Plexus EBNA-1 EA-D IgG: The document implies a direct comparison to a single commercially available ELISA, so a specific adjudication method like 2/3 majority would not apply in that instance.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This study is an in-vitro diagnostic device (IVD) performance study, comparing the device's output to established predicate tests, not measuring human reader performance with or without AI assistance.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, this was a standalone performance study. The Plexus EBV IgG Multi-Analyte Diagnostics device is an immunoassay kit that generates qualitative results based on fluorescence measurements and automated calculations using Plexus software (as stated in the "Interpretation of test results" section). Its performance was evaluated on its own, comparing its output to that of predicate immunoassay devices. It does not involve human interpretation as a primary output.

7. The Type of Ground Truth Used

The ground truth used was a composite gold standard based on multiple commercially available, FDA-cleared predicate serological assays and a serological algorithm. Specifically:

  • For VCA IgG: Consensus from three predicate immunoassays (ELISA, IFA, flow cytometry-based).
  • For EBNA-1 IgG and EA-D IgG: Results from a single predicate ELISA.
  • The overall "serological status" (e.g., Primary Acute, Late Acute, Previous Infection, No Infection) was classified using an algorithm based on a panel of results from commercially available ELISA assays (EBNA-1 IgG, VCA IgG, VCA IgM) and a heterophile rapid test. This represents an interpretation based on established diagnostic algorithms using multiple reference methods.

8. The Sample Size for the Training Set

The document does not provide information on a training set sample size. This study appears to be solely focused on validating the performance of the device against predicate methods on a test set. Immunoassays typically do not have a "training set" in the same way machine learning algorithms do, as their "learning" or calibration is part of the assay development and reagent formulation process. If any internal calibration or optimization was performed, it is not detailed in this summary.

9. How the Ground Truth for the Training Set Was Established

Since no training set details are provided, the method for establishing its ground truth is also not available in the document.

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Image /page/0/Picture/1 description: The image shows the logo for Focus Diagnostics. The logo consists of the word "FOCUS" in bold, sans-serif font, with the word "Diagnostics" in a smaller, non-bold font underneath. A curved, black shape is to the left of the word "FOCUS", and a line is underneath the word "FOCUS" and above the word "Diagnostics".

510(k) Summary of Safety and Effectiveness Plexus EBV IgG Multi-Analyte Diagnostics Catalog No. MP0500G Prepared Date: July 17, 2008

073382

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ApplicantFocus Diagnostics, Inc.10703 Progress WayCypress, California 90630USA
Establishment Registration No.2023365
Contact PersonConstance Bridgestel 714.220.1900fax 714.995.6921cbridges@focusdx.com
Summary DateJuly 17, 2008
Proprietary NamePlexus EBV IgG Multi-Analyte Diagnostics
Generic NameEpstein-Barr Virus Serological Assays
ClassificationClass I
Predicate DevicesDiamedix EBV VCA IgG ELISADiamedix EBV EBNA-1 IgG ELISADiamedix EBV EA-D IgG ELISAATHENA MULTI-LYTE EBV IGG TEST SYSTEMFocus EBV-VCA ANTIBODY (IGG) - IFA

JUL 2 8 2008#### Device Description

Multiplexed Immunoassay for the Qualitative Detection of Human IgG Antibodies to Epstein-Barr Virus

Intended Use

Focus Diagnostics' Plexus™ EBV IgG Multi-Analyte Diagnostics test kit is intended for qualitatively detecting the presence or absence of human IgG class antibodies to viral capsid antigen (VCA), early antigen- diffuse (EA-D), and nuclear antigen (EBNA-1) of Epstein-Barr virus in human sera. The test is indicated as an aid in the diagnosis of EBV infection and EBV-associated infectious mononucleosis.

The performance of this assay has not been established for use in the diagnosis of nasopharyngeal carcinoma and Burkit's lymphoma, for testing of immunocompromised patients, for use by a point of care facility or for use with automated equipment. This assay has not been evaluated for donor screening.

Test Principle

The Focus Diagnostics Plexus™ EBV IgG uses an Antigen Bead suspension that contains three distinct EBV antigen bead types (EA-D, VCA, & EBNA-1) and one process control bead type that fluoresce at different wavelengths and/or intensities.

The Focus Diagnostics Plexus™ EBV IgG is a three step procedure,

  • Patient sera are diluted, and the diluted sera are incubated with Antigen Beads. If EBV antibodies are present, 1. then the antibodies bind to the corresponding antigen beads.
    1. Phycoerythrin-conjugated goat Anti-human IgG (Conjugate) is added, binds to the bound EBV antibody (if present), and forms a Conjugate-EBV antibody-antigen bead sandwich.
    1. Fluorescence from each distinct EBV antigen bead type is measured and compared against a Cutoff Calibrator.

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Image /page/1/Picture/0 description: The image shows the logo for Focus Diagnostics. The logo consists of the word "FOCUS" in large, bold, sans-serif font, with the word "Diagnostics" in a smaller, sans-serif font underneath and a horizontal line separating the two words. To the left of the word "FOCUS" is a stylized, curved shape that resembles a swoosh or a checkmark.

510(k) Summary of Safety and Effectiveness Plexus EBV IgG Multi-Analyte Diagnostics Catalog No. MP0500G Prepared Date: July 17, 2008 Page 2 of 17

Comparison of Plexus EBV VCA IgG analyte to Predicates:

ItemDevicePredicates
NamePlexus™ EBV IgGMulti-AnalyteDiagnosticsDiamedix VCA IgG,ELISAAthena Multi-LyteEBV VCA IgG TestSystemFocus Epstein-BarrVirus VCA IFA IgG
Similarities between Device and Predicate
Intended useFocus Diagnostics'Plexus™ EBV (VCA)IgG Multi-Analyte isintended forqualitatively detectingthe presence orabsence of human IgGclass antibodies toviral capsid antigen(VCA), early antigen– diffuse pattern (EA-D), and nuclearantigen (EBNA-1) ofEpstein-Barr virus(EBV) in human sera.The test is indicatedas an aid in thediagnosis of EBVinfection and EBV-associated infectiousmononucleosis.Diamedix Corp EBVVCA IgG ELISA isintended for thequalitative and semi-quantitativedetermination of IgGantibodies to Epstein-Barr Virus(recombinant) ViralCapsid Antigen (EBV-VCA IgG) in humanserum by indirectenzyme immunoassay.The Is-EBV-VCA IgGtest kit may be used incombination with otherEpstein-Barrserologies, Viral CapsidAntigen (VCA) IgM,Epstein-Barr NuclearAntigen-1 (EBNA-1)IgG and IgM, EarlyAntigen-Diffuse (EA-D) IgG and IgM andheterophile antibody, asan aid in the diagnosisof infectiousmononucleosis (IM).The Zeus Scientific,Inc. AtheNA Multi-Lyte® EBV IgGTest System isintended for thequalitativedetection of IgGclass antibody tothree separate EBVAntigens (EBV-VCA gp-125, EBV-EA "total" andrecombinantEBNA-1) in humanserum using theAtheNA Multi-Lyte® System. Thetest system isintended to be usedasan aid in thelaboratorydiagnosis of EBV-associatedinfectiousmononucleosis andtoprovideepidemiologicalinformation on thedisease caused byEpstein-Barr virus.Focus Diagnostics'Epstein-Barr VirusViral CapsidAntigens (EBVVCA)IgGImmunofluorescenceAntibody (IFA) testis intended for thedetection andsemi-quantitation ofhuman IgGantibodies to theviral capsid antigens(VCA)of Epstein-Barr virusin human serum asan aid in the clinicaldiagnosis ofinfectiousmononucleosis.
Indications for useThe test is indicatedas an aid in thediagnosis of EBVinfection and EBV-associated infectiousmononucleosis.The device is indicatedfor use with patientswith the signs andsymptoms of infectiousmononucleosis.The ZeusScientific, Inc.AtheNA Multi-Lyte EBV IgGTest Systemis intended for thequalitativedetection of IgGclass antibody tothree separateEBVAntigens (EBVThe test is indicatedas an aid in theclinical diagnosis ofinfectiousmononucleosis.
ItemDevicePredicates
NamePlexus™ EBV IgGMulti-AnalyteDiagnosticsDiamedix VCA IgG,ELISAAthena Multi-LyteEBV VCA IgG TestSystemFocus Epstein-BarrVirus VCA IFA IgG
VCA, EBV-EAand EBNA-1) inhuman serumusing the AtheNAMulti-Lyte System. Thetest system isintended to beused with theseEBV IgG markersalongwith anti-EBVVCA IgM to aidin the laboratorydiagnosis ofEBV-associatedinfectiousmononucleosisand to provideepidemiologicalinformation onthe diseasescaused byEBV virus.
ImmunoglobulinTypeIgGIgGIgGIgG
Sample matrixSerumSerumSerumSerum
CLIA complexityHighHighHighHigh
Difference between Device and Predicate
AntigenEBV-VCA: VCA gp125, affinity purifiedantigenEBV-VCA:Recombinant 47 kDafusion half of p18EBV VCA gp25
StrainN/A- purified proteinN/A- RecombinantproteinN/A native proteinN/A- purifiedprotein
Host Cell LineEBV-VCA: Native(P3H3 orP3HR-1)EBV-VCA: E. coli(unknown)Unknown
MethodologyMultiplex MicrobeadImmunoassay(MMIA) based onLuminex XMAPtechnology.Enzyme Immunoassaytechnology.Multiplex beadimmunoassayImmunofluorescenceAntibody (IFA) test
ItemDevicePredicates
NamePlexus™ EBV IgGMulti-AnalyteDiagnosticsDiamedix VCA IgG,ELISAAthena Multi-LyteEBV VCA IgG TestSystemFocus Epstein-BarrVirus VCA IFA IgG
Interpretation oftest resultsPerform automatedcalculations usingPlexus software.Manual calculationAtheNA Multi-LyteinstrumentManual

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Image /page/2/Picture/0 description: The image shows the logo for Focus Diagnostics. The word "FOCUS" is in large, bold, sans-serif font. Above the word "FOCUS" is a curved, black shape that resembles a swoosh or checkmark. Below the word "FOCUS" is the word "Diagnostics" in a smaller font, underlined with a thin black line.

510(k) Summary of Safety and Effectiveness Plexus EBV IgG Multi-Analyte Diagnostics Catalog No. MP0500G Prepared Date: July 17, 2008 and the comments of the comments of the comments of the comments of the comments of the comments of the contribution of the contribution of the contribution of the contributi

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Image /page/3/Picture/0 description: The image shows the logo for Focus Diagnostics. The word "FOCUS" is in large, bold, sans-serif font. A curved line extends from the top left of the image, arcing over the word "FOCUS". Below the word "FOCUS" is the word "Diagnostics" in a smaller, sans-serif font, underlined with a thin line.

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Comparison of Plexus EBV EBNA-1 IgG analyte to Predicate:

ItemDevicePredicate
NamePlexus™ EBV IgG Multi-AnalyteDiagnosticsDiamedix EBNA-1 IgG ELISA
Similarity between Device and Predicate
Intended useFocus Diagnostics' Plexus™ EBV (EBNA-1) IgG Multi-Analyte is intended forqualitatively detecting the presence orabsence of human IgG class antibodies toviral capsid antigen (VCA), early antigen -diffuse pattern (EA-D), and nuclear antigen(EBNA-1) of Epstein-Barr virus (EBV) inhuman sera. The test is indicated as an aidin the diagnosis of EBV infection and EBV-associated infectious mononucleosis.Diamedix Corp EBV EBNA-1 IgG ELISAis intended the qualitative and semi-quantitative determination of IgG antibodiesto Epstein-BarrVirus (recombinant)Nuclear Antigen-1 (EBNA-1 IgG) in humanserum by indirect enzyme immunoassay.The Is-EBNA-1 IgG test kit may be used incombination with other Epstein-Barrserologies, viral capsid antigen (VCA) IgGand IgM, Epstein-Barr nuclear antigen-1(EBNA-1) IgM, early antigen-diffuse (EA-D) IgG and IgM and heterophile antibody,as an aid in the diagnosis of infectiousmononucleosis (IM).
Indications for useThe test is indicated as an aid in thediagnosis of EBV infection and EBV-associated infectious mononucleosis.The device is indicated for use with patientswith the signs and symptoms of infectiousmononucleosis.
Immunoglobulin TypeIgGIgG
Sample matrixSerumSerum
CLIA complexityHighHigh
Difference between Device and Predicate
StrainN/A- Recombinant proteinN/A- Recombinant protein
AntigenEBV-EBNA: Recombinant EBNA-1,truncated, 35 kDaEBV-EBNA-1: 27 kDa protein purifiednative protein (Recombinant protein)
Host Cell LineEBV-EBNA: Pichia pastorisEBV-EBNA: Native (unknown)

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Image /page/4/Picture/0 description: The image shows the logo for Focus Diagnostics. The word "FOCUS" is in large, bold, sans-serif font. Above and to the left of the word "FOCUS" is a black, curved shape that resembles a check mark. Below the word "FOCUS" is the word "Diagnostics" in a smaller, sans-serif font with a line above it.

510(k) Summary of Safety and Effectiveness Plexus EBV IgG Multi-Analyte Diagnostics Catalog No. MP0500G Prepared Date: July 17, 2008 Page 5 of 17

ItemDevicePredicate
NamePlexus™ EBV IgG Multi-AnalyteDiagnosticsDiamedix EBNA-1 IgG ELISA
MethodologyMultiplex Microbead Immunoassay(MMIA) based on Luminex XMAPtechnology.Enzyme Immunoassay technology.
Interpretation of testresultsPerform automated calculations usingManual calculation

Comparison of Plexus EBV EA-D IgG analyte to Predicate:

Comparison to Predicate

ItemDevicePredicate
NamePlexus™ EBV IgG Multi-AnalyteDiagnosticsDiamedix EA-D IgG ELISA
Similarity between Device and Predicate
Intended useFocus Diagnostics' Plexus™ EBV (EA-D)IgG Multi-Analyte is intended forqualitatively detecting the presence orabsence of human IgG class antibodies toviral capsid antigen (VCA), early antigen –diffuse pattern (EA-D), and nuclear antigen(EBNA-1) of Epstein-Barr virus (EBV) inhuman sera. The test is indicated as an aid inthe diagnosis of EBV infection and EBV-associated infectious mononucleosis.Diamedix Corp.EBV EA-D IgG ELISA isintended for the qualitative and semi-quantitative determination of IgG antibodiesto Epstein-Barr Virus (recombinant) EarlyAntigen Diffuse (EBV-EA-D IgG) in humanserum by indirect enzyme immunoassay. TheIs-EBV-EA-D IgG test kit may be used incombination with other Epstein-Barrserologies, Viral Capsid Antigen (VCA) IgGand IgM, Epstein-Barr Nuclear Antigen-1(EBNA-1) IgG and IgM, Early Antigen-Diffuse (EA-D) IgM and heterophileantibody, as an aid in the diagnosis ofinfectious mononucleosis (IM).
Indications for useThe test is indicated as an aid in the diagnosisof EBV infection and EBV-associatedinfectious mononucleosis.The device is indicated for use with patientswith the signs and symptoms of infectiousmononucleosis.
ImmunoglobulinTypeIgGIgG
Sample matrixSerumSerum
CLIA complexityHighHigh
Difference between Device and Predicate
AntigenEBV-EA: Recombinant EA-DEBV-EA: Recombinant EA-D 28 kDa

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Image /page/5/Picture/0 description: The image shows the logo for Focus Diagnostics. The logo consists of the word "FOCUS" in bold, sans-serif font, with the word "Diagnostics" in a smaller font size underneath. A curved, black shape is placed to the left of the word "FOCUS", adding a visual element to the logo.

510(k) Summary of Safety and Effectiveness Plexus EBV IgG Multi-Analyte Diagnostics Catalog No. MP0500G Prepared Date: July 17, 2008

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Comparison to Predicate

ItemDevicePredicate
NamePlexus™ EBV IgG Multi-AnalyteDiagnosticsDiamedix EA-D IgG ELISA
Host Cell LineEBV-EA: E. coliEBV-EA: E. coli (unknown)
StrainN/A- Recombinant proteinN/A- Recombinant protein
MethodologyMultiplex Microbead Immunoassay (MMIA)based on Luminex XMAP technology.Enzyme Immunoassay technology.
Interpretation oftest resultsPerform automated calculations using Plexussoftware.Manual calculation

EXPECTED VALUES

Outside investigators assessed the device with prospective masked sequential samples that were submitted for routine EBV testing esmants occasion ocean will vary depending on age, geographic location, testing method used and other factors. The comparator assay was performed by indirect enzyme immunoassay used in combination with other Epstein-Barr serologies (VCA) lgG and IgM, Epstein-Barr Nuclear Antigen-1 (EBNA-1) IgG, Early Antigen-Diffuse (EA-D) IgG and a helerophile rooid andiody test, The observed prevalence is in Table 1. The expected values are presented by age and gender in Tables 2-4. For all analytes, index values of <0.90 are negative, ≥0.90 to ≤ 1.10 are equivocal and > 1.10 are positives.

Table 1: Observed Prevalence - EBV Plexus
VCA IgGEBNA-1 IgGEA-D IgG
Positive66% (478/723)50% (362/723)17% (120/723)
Equivocal0% (3/723)0% (2/723)1% (9/723)
Negative25% (242/723)50% (349/723)82% (594/723)
AgeGenderPositiveEquivocalNegative
n%n%n%
<5F853.300.0746.7
<5M1747.200.01952.8
5-12F4343.011.05656.0
5-12M4648.400.04951.6
13-20F11870.700.04929.3
13-20M8263.110.84736.2
21-30F3797.400.012.6
21-30M1583.300.0316.7
31-40F1487.500.0212.5
31-40M1392.900.017.1

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Image /page/6/Picture/0 description: The image shows the logo for Focus Diagnostics. The logo features the word "FOCUS" in large, bold, sans-serif font, with a curved, swooping graphic element to the left of the word. Below "FOCUS" is the word "Diagnostics" in a smaller, sans-serif font, underlined with a thin black line. The overall design is simple and professional, suggesting a focus on precision and clarity.

r

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510(k) Summary of Safety and Effectiveness Plexus EBV IgG Multi-Analyte Diagnostics Catalog No. MP0500G Prepared Date: July 17, 2008

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AgeGenderPositiveEquivocalNegative
n%n%n%
41-50F1910000.000.019
41-50M1292.300.017.713
51-60F1593.800.016.316
51-60M872.700.0327.311
61-70F910000.000.09
61-70M880.000.0220.010
>70F710000.000.07
>70M777.8111.1111.19
Total47866.130.424233.5723
Table 3: EBV Plexus Results EBNA-1 IgG
AgeGendernPositiveEquivocalNegativeTotal
n%n%n%
<5F320.0000.01280.015
<5M1233.3000.02466.736
5-12F2828.0000.07272.0100
5-12M3637.9111.15861.195
13-20F8550.9000.08249.1167
13-20M5240.0000.07860.0130
21-30F2771.1000.01128.938
21-30M1055.6000.0844.418
31-40F1593.8000.016.316
31-40M1178.6000.0321.414
41-50F1789.5000.0210.519
41-50M1076.9000.0323.113
51-60F16100.0000.000.016
51-60M1090.9000.019.111
61-70F9100.0000.000.09
61-70M880.0000.0220.010
>70F685.7000.0114.37
>70M777.81111.1111.19
Total36250.1220.335949.7723

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Image /page/7/Picture/0 description: The image shows the logo for Focus Diagnostics. The word "FOCUS" is in large, bold, black letters. Above and to the left of the word is a curved black shape. Below the word "FOCUS" is the word "Diagnostics" in smaller, black letters with a line above it.

510(k) Summary of Safety and Effectiveness Plexus EBV IgG Multi-Analyte Diagnostics Catalog No. MP0500G Prepared Date: July 17, 2008

Page 8 of 17

Table 4: EBV Plexus Results EA-D IgG
PositiveEquivocalNegative
AgeGendern%n%n%Total
<5F16.716.71386.715
<5M411.100.03288.936
5-12F1111.000.08989.0100
5-12M99.511.18589.595
13-20F2716.221.213882.6167
13-20M2519.221.510379.2130
21-30F923.700.02976.338
21-30M527.800.01372.218
31-40F531.300.01168.816
31-40M214.300.01285.714
41-50F526.315.31368.419
41-50M17.717.71184.613
51-60F318.800.01381.316
51-60M327.319.1763.611
61-70F444.400.0555.69
61-70M330.000.0770.010
>70F342.900.0457.17
>70M00.000.09100.09
Total12016.6%91.2%59482.2%723

The table below summarizes the breakdown of the samples age and gender information. The distribution chart below exhibits the age distribution of all 873 samples included in the study.

Age Information:
Summary of FemaleSubjectsSummary of MaleSubjects
n474n399
mean20.0mean18.3
median16.0median14.0
min1min1
max88max87

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510(k) Summary of Safety and Effectiveness Plexus EBV IgG Multi-Analyte Diagnostics Catalog No. MP0500G Prepared Date: July 17, 2008 Page 9 of 17

Distribution of Patient Age 300 250 200 requency 150 100 ടറ 0

PERFORMANCE CHARACTERISTICS

Typical Antibody Response Classification

The table below summarizes a generally accepted algorithm for classifying the EBV infection status via EBV serologic profiles. For acute EBV serological status, booked agointin of blassilynig the LDV incodes to viral capsidade . FBV VCA (gM antibody disappear over approximalely four wiels. Hele capson aligging (very) hise rapuly. EBV vCH (gM fades rapidly over approximally four weeks . EBV EA-D JGG antibody shows a translent raise during acute infections and i undetectable after thee to six months. EDV EBVA-1 lgG antibody usually appears three months after intial infection and temains for life. The serological status was detemined by the use of commercially available in the milial medial. And relialis IgG. VCA JoS States was association of the doe of Gommercially available LCGS also Inter EDS andytes EBN-1.
Ight Hoterophile onlined the Heterophile antibody.

EBV SerologicalStatusEBNA-1 IgGEBV VCA IgGEBV EA-D IgGEBV VCA IgMHeterophileAntibody
NegativeNegativeNegativePositiveNegative
NegativeNegativeNegativePositivePositive
NegativeNegativeNegativePositivePositive
PrimaryAcuteNegativeNegativePositivePositiveNegative
NegativeNegativePositivePositivePositive
NegativePositivePositivePositiveNegative
AcuteNegativePositivePositivePositivePositive
NegativePositivePositiveNegativePositive
LateAcutePositivePositivePositiveNegativeNegative
PositivePositivePositivePositivePositive
PositivePositivePositivePositiveNegative
PositivePositiveNegativePositivePositive
PositivePositiveNegativePositiveNegative
NegativePositiveNegativePositiveNegative
RecoveringNegativePositivePositiveNegativeNegative
Past InfectionNegativePositiveNegativeNegativeNegative
PositivePositiveNegativeNegativeNegative
No InfectionNegativeNegativeNegativeNegativeNegative
IndeterminantCombinations not listed above (n =18)

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510(k) Summary of Safety and Effectivencss Plexus EBV IgG Multi-Analyte Diagnostics Catalog No. MP0500G Prepared Date: July 17, 2008

Comparison Studies

summarized by analyte.

Page 10 of 17 Performance of the Plexus EBNA-1 IgG and Plexus EA-D IgG analytes were tested against a commercially available ELISA test whereas performance of the Plexus EBV VCA IgG analyte was tested against a combination (hereaffer refered to as 'consenteus predicate') of a FDA-cleared commercially available ELISA, a FDA cleared commercially available immunofluros ent (JPA) est and a FDA cleared commercially available flow cytometry based immunoassay. For each sample, a consensus based alr (1) (2/3) was used to determine the predicate result for comparison with the Plexus VCA IgG result. The Plain Maria Ma United States testing sites: a hospital laboratory located in Northeast, a pediatic hospital laboratory located in the Mid-West, and Fous with serim samples in which EBV tests were ordered. The sera were sequentially submitted to the laboratory, and masked. Samples were collected at three sites and include both prospective (n = 723) and retrospective (n = 150) specimens. Retrospective samples were pre-selected based on EBV VCA Increasons of the form a FDA cleared device . Realts are

EBV VCA IgG vs Consensus Predicate: Comparison by Serological Status (Prospective Population Samples N = 723) Samples were collected and tested by the Northeast investigator (n = 350), Mid-West investigator (n=249),

The following table outlines the positive percent agreements across various serological classifications for prospective samples for VCA (gG analyte when the consensus predicate is used for VCA (gG analysis, Serological status was elermined by the use of commercially available ELISA assays for the EBV analytes EBNA-1 IgG, VCA IgG and VCA IgM and a commercially available heterophile rapid test for the Heterophile antibody.

Table 4: EBV VCA IgG Results
Serostatus byPredicatesnPlexus
Consensus PredicatePositiveEquivocalNegative% Agreement
AcutePrimaryAcutePositive575700100%(57/57), 95% CI:93.7-100%
Negative100133.3%(1/3), 95% CI:6.1-79.2%
No consensus¹2200NA
AcuteLateAcutePositive72701197.2%(70/72), 95% CI:90.4-99.2%
Negative0000NA
No consensus0000NA
RecoveringPositive1100100%(1/1), 95% CI:20.7-100%
Negative0000NA
No consensus0000NA
Previous InfectionPositive2922821996.6%(282/292), 95% CI:93.8-98.1%
Negative610583.3%(5/6), 95% CI:43.6-97%
No consensus0000NA
No InfectionPositive930630%(3/10), 95% CI:10.8-60.3%
Negative21713120393.5%(203/217), 95% CI:89.5-96.1%
No consensus¹1001NA
IndeterminatePositive50490198%(49/50), 95% CI:89.5-99.6%
Negative150015100%(15/15),95% CI:79.6-100%
No consensus0000NA

No consensus results: the combination of three predicates could not yeld a conclusive result for these samples – a 2/3 majority could not be obtained.

EBV EBNA-1 vs Predicate: Comparison by Serological Status (Prospective Population Samples N = 723)

Samples were collected and tested by the Northeast investigator (n=249) and Focus (n=249) and Focus (n=124),

The following table outlines the positive percent agreements across various serological classifications for prospective samples for EBNA-1 IgG analyte when a commercial ELISA test is used as a predicate for EBNA-1 IgG analysis. Serological status was deternined by the use of commercially available ELISA assays for the EBV analytes EBNA-1 IgG, VCA IgG and VCA IgM and a commercially available heterophile rapid test for the Heterophile antibody.

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510(k) Summary of Safety and Effectiveness Plexus EBV IgG Multi-Analyte Diagnostics Catalog No. MP0500G Prepared Date: July 17, 2008

Page 11 of 17

Table 5: EBV EBNA-1 IgG Results
Predicate ELISAPlexus
SerologicalStatus byPredicatesnPositiveEquivocalNegative% Agreement
PositivePositive0000NA
PrimaryAcuteEquivocal0000NA
AcuteNegative600060100%(60/60), 95% CI:94-100%
Positive69650494.2%(65/69), 95% CI:86-97.7%
LateAcuteEquivocal0000NA
Negative3003100%(3/3), 95% CI:43.8-100%
Positive0000NA
RecoveringEquivocal0000NA
Negative1001100%(1/1), 95% CI:20.7-100%
Positive28426621693.7%(266/284), 95% CI:90.2-96%
PreviousInfectionEquivocal0000NA
Negative14101392.9%(13/14), 95% CI:68.5-98.7%
Positive0000NA
No InfectionEquivocal0000NA
Negative2271022699.6%(226/227), 95% CI:97.5-99.9%
IndeterminatePositive36290776.3%(29/38), 95% CI:60.8-87%
Equivocal20020%(0/2), 95% CI:0-65.8%
Negative270027100%(27/27), 95% CI:87.5-100%

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Image /page/11/Picture/0 description: The image shows the logo for Focus Diagnostics. The logo features a stylized black swoosh on the left side, followed by the word "FOCUS" in bold, sans-serif font. Below "FOCUS" is the word "Diagnostics" in a smaller, non-bold, sans-serif font, underlined with a thin black line.

510(k) Summary of Safety and Effectiveness Plexus EBV IgG Multi-Analyte Diagnostics Catalog No. MP0500G

Prepared Date: July 17, 2008 Page 12 of 17

EBV EA-D vs Predicate: Comparison by Serological Status (Prospective Population Samples N = 723) Samples were collected and tested by the Northeast investigator (nestigator (nvestigator (nvestigator (n=249) and Focus (n=124).

The following table outlines the positive percent agreements across various serological classifications for prospective samples for EA-D IgG and regal EU SA Lest is used as a predicate for EA-D IgG analysis. Serological status and determined by the use of commercially available ELISA assas for the EBV andres EBNA-1 (gG, VCA IgG, EA-D (gG, EA-D (gG, EA-D (gG, EA-D (gG, EA-D (gG, EA-D (gG, EA-D (gG, EA-D IgM and a commercially available heterophile rapid test for the Heterophile antibody.

Table 6: EBV EA-D IgG Results
SerologicalStatus byPredicatesPlexus% Agreement
Predicate ELISAnPositiveEquivocalNegative
AcutePositive43400393%(40/43), 95% CI:81.4-97.6%
PrimaryAcuteEquivocal0000NA
Negative17401376.5%(13/17), 95% CI:52.7-90.4%
AcutePositive51411980.4%(41/51), 95% CI:67.5-89%
LateAcuteEquivocal0000NA
Negative21221781%(17/21), 95% CI:60-92.3%
RecoveringPositive10010%(0/1), 95% CI:0-79.3%
Equivocal0000NA
Negative0000NA
Previous InfectionPositive0000NA
Equivocal0000NA
Negative29811128696%(286/298), 95% CI:93.1-97.7%
No InfectionPositive0000NA
Equivocal0000NA
Negative2271322398.2%(223/227), 95% CI:95.6-99.3%
IndeterminatePositive1270526.9%(7/26), 95% CI:13.7-46.1%
Equivocal30142146.3%(2/32), 95% CI:1.7-20.1%
Negative23002362.2%(23/37), 95% CI:46.1-75.9%

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Image /page/12/Picture/0 description: The image shows the logo for Focus Diagnostics. The word "FOCUS" is in large, bold, sans-serif font. Below "FOCUS" is the word "Diagnostics" in a smaller font with a line above it. To the left of the word "FOCUS" is a black swoosh.

510(k) Summary of Safety and Effectiveness Plexus EBV IgG Multi-Analyte Diagnostics Catalog No. MP0500G

Prepared Date: July 17, 2008

Page 13 of 17

EBV VCA IgG vs Consensus Predicate: Comparison by Serological Status (Retrospective Presumed Acute Population Samples N = 150)

Samples were collected and tested by Mid-West investigator (n=150).

The following table outlines the positive percent agreements across various serological classifications for retrospective samples for VCA IgG analyte when the consensus predicate is used for VCA IgG analysis. Serological status was delermined by the use of commercially available ELISA assays for the EBV analytes EBNA-1 IgG, VCA IgG and VCA IgM and a commercially available heterophile rapid test for the Heterophile antibody.

Table 7: EBV VCA IgG Results
Serostatus byPredicatesConsensus PredicatePlexus% Agreement
nPositiveEquivocalNegative
AcutePositive106991693.4%(99/106), 95% CI:87-96.8%
Negative0000NA
No consensus0000NA
AcutePositive8800100%(8/8), 95% CI:67.6-100%
Negative0000NA
No consensus0000NA
No InfectionPositive1100100%(1/1), 95% CI:20.7-100%
Negative11000%(0/1), 95% CI:0-79.3%
No consensus0000NA
IndeterminatePositive33310293.9%(31/33), 95% CI:80.4-98.3%
Negative0000NA
No consensus11100NA

No consensus results the combination of three predicates could not yeld a conclusive result for these samples - a 2/3 majority could not be obtained.

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Image /page/13/Picture/0 description: The image shows the logo for Focus Diagnostics. The word "FOCUS" is in large, bold, sans-serif font. To the left of the word is a curved, black shape that resembles a swoosh. Below the word "FOCUS" is the word "Diagnostics" in a smaller, sans-serif font with a line above it.

510(k) Summary of Safety and Effectiveness

Plexus EBV IgG Multi-Analyte Diagnostics Catalog No. MP0500G

Prepared Date: July 17, 2008 Page 14 of 17

EBY EBNA-1 vs Predicate: Comparison by Serological Status (Retrospective Presumed Acute Population Samples N = 150) Samples were collected and tested by Mid-West investigator (n=150).

The following table outlines the positive percent agreements across various serological classifications for retrospective me lollowing table damos the nagative position is position in the many in EBNA-1 lgC analysis. Serological status was delermined by the use of commercially available ELISA assays for the EBV analytes EBNA-1 1gG, VCA IgG and VCA IgM and a commercially available heterophile rapid test for the Heterophile antibody.

Table 8: EBV EBNA-1 IgG Results
Predicate ELISAPlexus
SerologicalStatus byPredicatesnPositiveEquivocalNegative% Agreement
AcutePrimaryAcutePositive0000NA
Equivocal0000NA
Negative1061010599.1%(105/106), 95% CI:94.8-99.8%
AcuteLateAcutePositive40040%(0/4), 95% CI:0-49%
Equivocal0000NA
Negative4004100%(4/4), 95% CI:51-100%
No InfectionPositive0000NA
Equivocal0000NA
Negative2002100%(2/2), 95% CI:34.2-100%
IndeterminatePositive40040%(0/8), 95% CI:0-32.4%
Equivocal40040%(0/4), 95% CI:0-49.0%
Negative260026100%(26/26), 95% CI:87.1-100%

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Image /page/14/Picture/0 description: The image shows the logo for Focus Diagnostics. The word "FOCUS" is in large, bold, sans-serif font. A curved, black shape is to the left of the word. Below "FOCUS" is the word "Diagnostics" in a smaller, sans-serif font with a line above it.

510(k) Summary of Safety and Effectiveness

Plexus EBV IgG Multi-Analyte Diagnostics Catalog No. MP0500G

Prepared Date: July 17, 2008 Page 15 of 17

EBY EA-D vs Predicate: Comparison by Serological Status (Retrospective Presumed Acute Population Samples N = 150) Samples were collected and tested by Mid-West investigator (n=150).

The following table outlines the positive percent agreements across various serological classifications for retrospective samples for EA-D IgG analyte when a commercial ELISA test is used as a predicate for EA-D IgG analysis. Serological status was determined by the use of commercially available ELISA assays for the EBV analytes EBNA-1 IgG, VCA IgG, EA-D IgG and VCA IgM and a commercially available heterophile rapid test for the Heterophile antibody.

Predicate ELISAPlexus% Agreement
SerologicalStatus byPredicatesnPositiveEquivocalNegative
AcutePrimaryAcutePositive61571393.4%(57/61), 95% CI:84.3-97.4%
Equivocal0000NA
Negative45733577.8%(35/45), 95% CI:63.7-87.5%
AcuteLateAcutePositive3300100%(3/3), 95% CI:43.8-100%
Equivocal0000NA
Negative510480%(4/5), 95% CI:37.6-96.4%
No InfectionPositive0000NA
Equivocal0000NA
Negative2002100%(2/2), 95% CI:34.2-100%
IndeterminatePositive1080266.7%(8/12), 95% CI:39.1-86.2%
Equivocal1412020%(0/14), 95% CI:0-21.5%
Negative1001940.9%(9/22), 95% CI:23.3-61.3%

Inter-laboratory, Intra-assay and Inter-assay Reproducibility

The interlintra-assay reproducibility and the inter-laboratory reproducibility testing were performed at three laboratories. Each of the three laboratories tested twelve samples in triplicate on five different days. The study are summarized in the table below.

Table 16: Inter-laboratory, Intra-assay and Inter-assay Reproducibility
Plexus VCA IgGPlexus EBNA IgGPlexus EA IgG
IDIntra-assay & Inter-assay %CVInter-LabIDIntra-assay & Inter-assay %CVInter-LabIDIntra-assay & Inter-assay %CVInter-Lab
Mean IndexIntra-assayInter-assayMean Index% CVMean IndexIntra-assayInter-assayMean Index% CVMean IndexIntra-assayInter-assayMean Index% CV
55.382.1%8.1%5.387.4%126.662.1%8.7%6.668.9%124.423.9%7.5%4.422.0%
195.122.9%10.0%5.1210.1%154.414.1%6.9%4.425.0%42.693.6%19.9%2.697.0%
205.022.4%8.4%5.038.1%83.662.5%6.7%3.665.8%161.884.7%7.5%1.884.7%
64.213.2%6.7%4.203.7%42.685.6%18.3%2.677.8%151.395.6%15.6%1.3915.7%
43.374.3%16.6%3.372.5%182.053.8%9.0%2.058.6%190.996.0%12.0%0.997.9%
162.214.1%28.4%2.2227.0%51.843.7%8.0%1.844.8%80.913.7%8.6%0.912.1%
182.114.0%6.0%2.113.7%61.475.1%11.8%1.4611.7%50.764.7%12.6%0.765.6%
22.013.9%7.9%2.014.4%21.004.0%13.4%1.0013.6%200.635.3%8.5%0.632.6%
111.166.3%13.3%1.1611.9%30.816.1%16.0%0.8111.9%180.325.3%9.6%0.326.6%
81.114.7%77.0%1.1231.1%160.776.1%59.1%0.7750.9%60.296.1%33.8%0.294.7%
150.388.7%19.6%0.3813.4%200.655.4%11.1%0.658.9%20.215.2%61.9%0.2112.4%
10.1718.2%69.2%0.1759.3%90.159.8%304.1%0.15134%30.218.2%64.6%0.2110.1%
90.1115.2%117.9%0.1172.5%190.117.8%23.8%0.1119.8%110.186.6%106.1%0.1827.0%
31.715.4%11.4%1.715.8%10.0714.0%41.1%0.0734.7%10.159.1%96.5%0.1516.9%
124.692.6%7.7%4.695.4%110.0411.2%32.9%0.0423.1%90.108.0%40.1%0.1028.1%

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Image /page/15/Picture/0 description: The image shows the logo for Focus Diagnostics. The logo features the word "FOCUS" in bold, uppercase letters, with a curved graphic element to the left of the word. Below "FOCUS" is the word "Diagnostics" in a smaller, non-bold font, underlined with a thin line.

510(k) Summary of Safety and Effectiveness Plexus EBV IgG Multi-Analyte Diagnostics Catalog No. MP0500G Prepared Date: July 17, 2008 Page 16 of 17

Inter-Lot Reproducibility

The inter-lot reproducibility was evaluated with fifteen (15) samples in three (3) lots of Plexus EBV kit. The results of the study are summarized in the table below.

Table 10: Inter-lot Reproducibility
Plexus VCA IgGPlexus EBNA IgGPlexus EA-D IgG
IDMean%CVIDMean%CVIDMean%CV
56.003.2%127.353.6%124.515.3%
195.882.3%154.764.6%42.863.3%
205.572.4%84.014.5%161.842.0%
125.083.7%42.624.8%151.369.0%
64.663.3%182.396.7%191.004.6%
43.611.3%51.663.5%80.857.2%
182.083.7%61.445.8%50.684.8%
22.012.4%20.935.0%200.592.3%
161.774.8%30.742.3%180.308.6%
31.724.0%200.583.5%60.294.2%
111.003.8%160.363.2%20.218.3%
80.752.8%190.107.7%30.205.8%
150.317.8%10.065.7%110.1814.4%
10.117.7%110.048.1%10.1510.8%
90.020.0%90.0230.0%90.116.4%

Cross-Reactivity

A cross-reactivity study was performed to determine if samples from various disease states and other potentially cross-reactivity factors interfere with test results when tested with the Plexus EBV IgG kit. A panel of (ANA= 28, CMV= 31, HSV-2=13, HSV-6= 4, Rubeola Virus =1, Rubella Virus=39, Toxoplasma gondii =19, and VZA= 35) samples for each cross reactant were evaluated for possible cross reactivity with the Plexus EBV IgG kit for each of the three (VCA, EA-D and EBNA-1) IgG analyte. Of the 107 samples tested, 41 were prescreened for EBV IgG negativity. Because of the high prevalence of EBV IgG antibodies in Of the for bangles total 11 The proof only in 19 mornerially available ELISA. The majority of all samples that did elicit a positive result were also confirmed positive by the corresponding commercially available ELISA, indicating reactivity to EV IgG antibodies rather than cross reactivity with a potentially interfering factor.

Cross ReactivesNMethodEBV VCA IgGEBV EBNA IgGEBV EAD IgG
PositiveEquivocalNegativePositiveEquivocalNegativePositiveEquivocalNegative
ANA28Plexus270128008020
ELISA280028005518
Discrepants1065
Cytomegalovirus(CMV)Plexus241624074027
31ELISA260525063127
Discrepants21121
HSV-129Plexus271126023125
ELISA270228113026
Discrepants212111
HSV-213Plexus13001201238
ELISA130013002110
Discrepants0144
HHV-6Plexus004004004
4ELISA004004004
Discrepants000
Measles(Rubeola)Plexus001001001
1ELISA001001001
Discrepants000

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510(k) Summary of Safety and Effectiveness Plexus EBV IgG Multi-Analyte Diagnostics Catalog No. MP0500G Prepared Date: July 17, 2008 Page 17 of 17

Table 11: Cross-Reactivity
Cross ReactivesNMethodEBV VCA IgGEBV EBNA IgGEBV EAD IgG
PositiveEquivocalNegativePositiveEquivocalNegativePositiveEquivocalNegative
Mumps1Plexus001001001
ELISA001001001
Discrepants000
Rubella Virus39Plexus26013251134134
ELISA26112270123234
Discrepants812111
Toxoplasmagondii19Plexus170218011414
ELISA190018011216
Discrepants2044
Varicella-zoster(VZV)35Plexus2609220134130
ELISA24011220134229
Discrepants4043

One Equivocal Sample; Two Equivocal Samples; Three Equivocal Samples; Four Equivocal Samples

Sample Storage and Handling

Fifteen (15) neqative and positive for EBV IgG samples were used to assess the reactivity of unfrozen samples that were frozen and thawed for up to five cycles. No effect was observed for any of the freeze-thaw cycling in either the positive or negative sample.

Interference

The test performance was evaluated with the presence of interfering substances. Four samples, two positive for EBV IgG antibodies by Plexus EBV IgG were used in the study. Baseline levels for triglycerides, albumin, bilirubin, and hemoglobin were established for each sample. The remaining serum was spiked with purchased interfering substances at levels that exceeded the expected human range. The spiked samples were tested again in the assay to determine if the elevated levels of interfering substances affected the assay. No interference was observed for any of the interfering substances in either the positive or negative sample.

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Image /page/17/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo features a stylized eagle with three lines forming its body and wings. The eagle is positioned to the right of the department's name, which is arranged in a circular pattern around the logo. The text reads 'DEPARTMENT OF HEALTH & HUMAN SERVICES - USA'.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Focus Diagnostics, Inc. C/O Constance Bridges 10703 Progress Way Cypress, California 90630

JUL 2 8 2008

Re: K073382

Trade/Device Name: Plexus EBV IgG Multi-Analyte Diagnostics Regulation Number: 21 CFR 866.3235 Regulation Name: Epstein-Barr Virus Serological Device Regulatory Class: Class I Product Code: LSE Dated: November 30, 2007 Received: December 3, 2007

Dear Ms. Bridges:

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 or uny I eath 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 or requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter requirements begin marketing your device as described in your Section 510(k) premarket

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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 vour device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at 240-276-0450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at 240-276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at 240-276-3464. 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/industry/support/index.html.

Sincerely yours,

Sally attaym

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

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510(k) Number (if known):

KO73382

Device Name:

Plexus EBV IgG Multi-Analyte Diagnostics

Focus Diagnostics' Plexus™ EBV IgG Multi-Analyte Diagnostics test kit Indications for Use: is intended for qualitatively detecting the presence or absence of human IgG class antibodies to viral capsid antigen (VCA), early antigen- diffuse (EA-D), and nuclear antigen (EBNA-1) of Epstein-Barr virus in human sera. The test is indicated as an aid in the diagnosis of EBV infection and EBV-associated infectious mononucleosis.

The performance of this assay has not been established for use in the diagnosis of nasopharyngeal carcinoma and Burkitt's lymphoma, for testing of immunocompromised patients, for use by a point of care facility or for use with automated equipment. This assay has not been evaluated for donor screening.

Prescription Use × (Part 21 CFR 801 Subpart D) AND/OR

Over-the-Counter Use (21 CFR 807 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Soucas
Division Sign-Off

ffice of In Vitro Diaan Evaluation and Sc

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510(k) K073362

§ 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).