Elecsys EBV EBNA IgG

{0} [LOGO] FDA U.S. FOOD & DRUG ADMINISTRATION # 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION ## DECISION SUMMARY ASSAY AND INSTRUMENT ### I Background Information: A 510(k) Number K260221 B Applicant Roche Diagnostics C Proprietary and Established Names Elecsys EBV EBNA IgG D Regulatory Information | Product Code(s) | Classification | Regulation Section | Panel | | --- | --- | --- | --- | | LLM, LSE, MCD | Class I, reserved | 21 CFR 866.3235 - Epstein-Barr Virus Serological Reagents | MI - Microbiology | ### II Submission/Device Overview: A Purpose for Submission: To obtain clearance of a new device B Measurand: Epstein Barr virus IgG antibodies to the EBV Nuclear Antigen (EBNA) IgG device C Type of Test: Fully automated qualitative chemiluminescent immunoassay CLIA) ### III Intended Use/Indications for Use: A Intended Use(s): Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993-0002 www.fda.gov {1} See Indications for Use below. ### B Indication(s) for Use: Immunoassay for the in vitro qualitative detection of IgG antibodies to Epstein-Barr virus Nuclear Antigen-1 (EBNA-1) in human serum and plasma. When performed in conjunction with other Epstein-Barr virus markers, this assay is intended for use as an aid in the diagnosis of Epstein-Barr virus infection, such as infectious mononucleosis. The electrochemiluminescence immunoassay “ECLIA” is intended for use on cobas e immunoassay analyzers. ### C Special Conditions for Use Statement(s): Rx - For Prescription Use Only ### D Special Instrument Requirements: cobas e 801 Analyzer ### IV Device/System Characteristics: ### A Device Description: The Elecsys EBV EBNA IgG is an electrochemiluminescence immunoassay (ECLIA) to detect IgG antibodies to EBV EBNA. Elecsys EBV EBNA IgG kit is comprised of a cobas e pack and the lot-specific calibrators, EBVEBNA Cal1 and EBVEBNA Cal2The cobas e pack consists of Reagent 1 (R1), Reagent 2 (R2) and Microparticles (M): - R1 contains biotinylated EBNA-1-specific antigen - R2 contains EBV EBNA-1-specific antigen labeled with ruthenium complex - M contains streptavidin-coated microparticles. Calibrators are a two-concentration level set, negative calibrator 1 and positive calibrator 2. The PreciControl EBV EBNA IgG kits are required to perform the assay and are available separately from the cobas e pack. There are 2 levels of control material provided: Negative control, EBVEBN1, and positive control EBVEBN2. ### B Principle of Operation: The Elecsys EBV EBNA IgG is a qualitative, serological, sandwich principle immunoassay to be used on the cobas e 801 immunoassay analyzer with an overall 18-minute test time. - 1st incubation: 6 μL of sample, biotinylated recombinant EBNA-1 specific antigens and EBNA-1 specific recombinant antigens labeled with a ruthenium complex form a sandwich complex. K260221 - Page 2 of 15 {2} - 2nd incubation: After addition of streptavidin-coated microparticles, the complex becomes bound to the solid phase via interaction of biotin and streptavidin. - microparticles bound to the sandwich complex are magnetically captured onto the surface of the electrode. Application of a voltage to the electrode then induces chemiluminescent emission which is measured by a photomultiplier. - Results are determined automatically by comparing the electrochemiluminescence signal obtained from the reaction product of the sample with the signal of the cutoff value obtained by calibration. # **Interpretation of results** Results obtained with the Elecsys EBV EBNA IgG assay can be interpreted as follows: | Numeric result | Result message | Interpretation | | --- | --- | --- | | COI < 1.0 | Non-reactive | Negative for EBV-EBNA-specific IgG | | COI ≥ 1.0 | Reactive | Positive for EBV-EBNA-specific IgG | # **C Instrument Description Information:** 1. Instrument Name: cobas e 801 analyzer 2. Specimen Identification: The system automatically reads barcode information from specimen tubes to identify and track samples throughout the testing process. 3. Specimen Sampling and Handling: The cobas e 801 analyzer handles samples through an automated rack-based system, supporting continuous loading/unloading of up to 300 samples per hour for high-throughput immunoassays. 4. Calibration: Calibration is performed as follows: - once per reagent lot using EBVEBNA Cal1, EBVEBNA Cal2 and fresh reagent - every 12 weeks when using the same reagent lot - every 28 days when using the same cobas e pack on the analyzer - as required, such as when quality control findings are outside the defined limits. 5. Quality Control: The PreciControl EBV EBNA IgG QC is run: - every 24 hours when the test is in use - ones per cobas e pack - following a valid calibration. K260221 - Page 3 of 15 {3} Acceptable performance is achieved when the analyte values obtained are within the expected control interval for the system. # V Substantial Equivalence Information: # A Predicate Device Name(s): LIASON EBNA IgG # B Predicate 510(k) Number(s): K040120 # C Comparison with Predicate(s): | Device & Predicate Device(s): | K040120 Predicate Device | K260221 Candidate Device | | --- | --- | --- | | Device Trade Name | LIASON EBNA IgG | Elecsys EBV EBNA IgG | | General Device Characteristic Similarities | | | | Intended Use/Indications For Use | The LIAISON EBNA IgG assay uses chemiluminescent immunoassay (CLIA) technology on the LIAISON Analyzer family* for the qualitative determination of specific IgG antibodies to Epstein-Barr virus (EBV) viral capsid antigen (VCA) nuclear antigen synthetic peptide (EBNA-1) in human serum. When performed in conjunction with other EBV markers, this assay can be used as an aid in the clinical laboratory diagnosis of Epstein-Barr Viral Syndrome in patients with signs and symptoms of EBV infection such as infectious mononucleosis. Caution: U.S. Federal Law restricts this device to sale by or on the order of a licensed practitioner. 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 | Immunoassay for the in vitro qualitative detection of IgG antibodies to Epstein-Barr virus Nuclear Antigen-1 (EBNA-1) in human serum and plasma. When performed in conjunction with other Epstein-Barr virus markers, this assay is intended for use as an aid in the diagnosis of Epstein-Barr virus infection, such as infectious mononucleosis. The electrochemiluminescence immunoassay “ECLIA” is intended for use on cobas e immunoassay analyzers. | K260221 - Page 4 of 15 {4} | | nasopharyngeal carcinoma, Burkitt's lymphoma, and other EBV-associated lymphomas. | | | --- | --- | --- | | Measurand | IgG antibodies to the Nuclear Antigen-1 (EBNA-1) of EBV | Same | | Assay Type | Qualitative | Same | | Technology | Chemiluminescence immunoassay (CLIA) | Same | | General Device Characteristic Differences | | | | Sample Matrix | Serum | Serum Li-heparin, K2-EDTA, K3-EDTA | | Result Analysis | • < 18.0 U/mL Negative • 18.0 to 21.9 U/mL Equivocal • ≥ 22.0 U/mL Positive | COI < 1.0 non-reactive COI ≥ 1.0 reactive | | Application/Test Time | 30 minutes LIAISON Analyzer 15 minutes LIAISON XL Analyzer | 18 minutes | | Reagent Composition | Coated Magnetic particles Conjugate: Mouse monoclonal antibodies to human IgG | Streptavidin-coated microparticles R1: Biotinylated EBNA-1-specific antigen R2: EBNA-1 specific antigen with ruthenium complex | | Calibrator | Human serum/defibrinated plasma containing low and high EBV EBNA IgG levels | Human serum lyophilized positive and negative for EBV EBNA IgG | | Instrument Platform | LIAISON Analyzer LIAISON XL Analyzer | cobas e analytical unit | ### VI Standards/Guidance Documents Referenced: - CLSI EP05-A3 Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline - Third Edition (Reaffirmed: September 2019). - CLSI EP09c Measurement Procedure Comparison and Bias Estimation Using Patient Samples - 3rd Edition (2018). - CLSI EP07 Interference Testing in Clinical Chemistry; Approved Guideline - 3rd Edition (2018). - CLSI EP37 Supplemental Tables for Interference Testing in Clinical Chemistry - 1st Edition (2018). - CLSI EP25-A (Replaces EP25-P) Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline (2009). - CLSI EP12-A2 User Protocol for Evaluation of Qualitative Test Performance; Approved Guideline - 2nd Edition (2008). - CLSI I/LA21-A2 Clinical Evaluation of Immunoassays; Approved Guideline - 2nd Edition. ### VII Performance Characteristics (if/when applicable): K260221 - Page 5 of 15 {5} # A Analytical Performance: # 1. Precision/Reproducibility: # A. Within-Laboratory Precision Study A precision study was conducted to establish within-laboratory precision of the Elecsys EBV EBNA IgG on the cobas e 801 analyzer. Five human serum samples covering the analytical range and two controls were tested at: 1 run per day, in replicate of 4 each for 21 days (n = 84). In addition, a study was conducted to demonstrate lot-to-lot variability between three lots of Elecsys EBV EBNA IgG at 1 run per day for 5 days on one cobas e 801 analyzer. Precision study results on cobas e 801 analyzer are summarized in Tables 1 and 2. Table 1. Elecsys EBV EBNA IgG within-laboratory precision study results on the cobas e 801 | Sample | N | Mean COI | Repeatability | | Between-Run/Day | | Within-Laboratory | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | | | SD | % CV | SD | % CV | SD | % CV | | Sample 1 | 84 | 0.039 | 0.001 | 2.69 | 0.0003 | 0.679 | 0.001 | 2.78 | | Sample 2 | 84 | 0.936 | 0.015 | 1.60 | 0.020 | 2.18 | 0.025 | 2.70 | | Sample 3 | 84 | 1.22 | 0.019 | 1.57 | 0.026 | 2.10 | 0.032 | 2.62 | | Sample 4 | 84 | 3.27 | 0.095 | 2.90 | 0.066 | 2.03 | 0.116 | 3.54 | | Sample 5 | 84 | 86.2 | 1.14 | 1.32 | 2.27 | 2.64 | 2.54 | 2.95 | | PC EBV EBN1 | 84 | 0.036 | 0.001 | 4.09 | 0.0000 | 0.0000 | 0.001 | 4.09 | | PC EBV EBN2 | 84 | 3.26 | 0.043 | 1.31 | 0.065 | 2.01 | 0.078 | 2.40 | Table 2. Elecsys EBV EBNA IgG 5-day Lot-to-Lot Precision on cobas e 801 | Sample | N | Mean COI | Repeatability | | Between-Run/Day | | Between-Lot | | Within-Laboratory | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | | | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) | | Sample 1 | 75 | 0.057 | 0.001 | 1.8 | 0.0007 | 1.3 | 0.0323 | 5.7 | 0.003 | 6.1 | | Sample 2 | 75 | 0.051 | 0.0008 | 1.6 | 0.0148 | 3.8 | 0.0387 | 10.0 | 0.0419 | 10.9 | | Sample 3 | 75 | 0.965 | 0.00381 | 1.3 | 0.0265 | 4.0 | 0.0000 | 0.0 | 0.0278 | 4.2 | | Sample 4 | 75 | 0.880 | 0.00828 | 1.2 | 0.0260 | 3.7 | 0.0297 | 4.2 | 0.0404 | 5.7 | | Sample 5 | 75 | 1.25 | 0.00886 | 1.0 | 0.0318 | 3.7 | 0.0525 | 6.0 | 0.062 | 7.1 | | Sample 6 | 75 | 1.25 | 0.00903 | 1.0 | 0.0336 | 3.8 | 0.00555 | 0.6 | 0.0352 | 4 | K260221 - Page 6 of 15 {6} | Sample 7 | 75 | 5.65 | 0.0401 | 1.4 | 0.132 | 4.7 | 0.0941 | 3.4 | 0.167 | 6 | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Sample 8 | 75 | 35.2 | 0.415 | 2.5 | 0.679 | 4.1 | 1.09 | 6.6 | 1.35 | 8.2 | | Sample 9 | 75 | 145 | 1.17 | 1.9 | 2.89 | 4.7 | 4.07 | 6.7 | 5.12 | 8.4 | | PC EBV EBN1 | 75 | 0.047 | 0.00707 | 1.7 | 0.0162 | 3.9 | 0.0503 | 12.0 | 0.0533 | 12.7 | | PC EBV EBN2 | 75 | 3.05 | 0.0587 | 0.9 | 0.293 | 4.3 | 0.326 | 4.8 | 0.442 | 6.5 | ### B. Reproducibility Reproducibility of the Elecsys EBV EBNA IgG on the cobas e 801 analyzer was determined with a panel of 5 human sera and 2 controls. Samples were measured in triplicate determination using 1 reagent lot, in 2 runs per day for 5 days at 3 sites (n = 90). Variance components were calculated absolutely, as well as in relative contribution to the total size variance. The reproducibility study results on the cobas e 801 analyzer are summarized in Tables 3. Table 3. Elecsys EBV EBNA IgG Reproducibility on the cobas e 801 | | | | Repeatability | | Between Run | | Between Day | | Between Sites | | Reproducibility | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Sample | N | Mean COI | SD COI | CV % | SD COI | CV % | SD COI | CV % | SD COI | CV % | SD COI | CV % | | HSP01 | 90 | 0.042 | 0.001 | 3.22 | 0.000 | 0.00 | 0.001 | 1.21 | 0.001 | 1.28 | 0.002 | 3.67 | | HSP02 | 90 | 0.761 | 0.015 | 1.93 | 0.012 | 1.52 | 0.000 | 0.00 | 0.025 | 3.25 | 0.031 | 4.07 | | HSP03 | 90 | 1.29 | 0.021 | 1.60 | 0.013 | 1.02 | 0.013 | 1.02 | 0.034 | 2.64 | 0.044 | 3.41 | | HSP04 | 90 | 25.3 | 0.373 | 1.47 | 0.435 | 1.72 | 0.000 | 0.00 | 0.613 | 2.42 | 0.839 | 3.31 | | HSP05 | 90 | 59.6 | 0.828 | 1.39 | 0.600 | 1.01 | 0.318 | 0.534 | 1.48 | 2.49 | 1.83 | 3.07 | | PC EBV- EBN1 | 90 | 0.044 | 0.002 | 4.32 | 0.000 | 0.00 | 0.000 | 1.13 | 0.000 | 0.742 | 0.002 | 4.53 | | PC EBV- EBN2 | 90 | 2.74 | 0.037 | 1.34 | 0.034 | 1.23 | 0.023 | 0.822 | 0.077 | 2.80 | 0.094 | 3.44 | ### 2. Linearity: Not applicable as the device is a qualitative assay ### 3. Analytical Specificity/Interference: ### A. Cross-Reactivity Potentially cross-reacting samples, consisting of characterized positive for potentially cross-reacting analytes, were tested with the Elecsys EBV EBNA IgG assay. A total of K260221 - Page 7 of 15 {7} 678 samples were tested. The following results were obtained. Table 4. Cross-Reactivity Study Results | | | Elecsys EBV EBNA IgG | | | --- | --- | --- | --- | | Cross-Reactants | Number of samples tested | Number of Reactive | Number of Non-reactive | | CMV | 61 | 2 | 59 | | Rubella | 217 | 3 | 214 | | Toxoplasmosis | 7 | 0 | 7 | | HAV | 112 | 2 | 110 | | HBV | 123 | 0 | 123 | | HIV^{A)} | 5 | 0 | 5 | | HCV^{A)} | 6 | 0 | 6 | | HHV6 | 17 | 0 | 17 | | Treponema pallidum^{A)} | 5 | 0 | 5 | | Measles | 6 | 0 | 6 | | Mumps | 17 | 0 | 17 | | Borrelia burgdorferi | 5 | 0 | 5 | | VZV | 13 | 0 | 13 | | Parvovirus B19 | 8 | 0 | 8 | | SLE/dsDNA^{A)} | 6 | 0 | 6 | | HEV | 14 | 0 | 14 | | ANA^{A)} | 6 | 0 | 6 | | HSV-1 | 27 | 1 | 26 | | HSV-2 | 7 | 0 | 7 | | EBV IgM | 8 | 0 | 8 | | EBV VCA IgG | 8 | 0 | 8 | A) 5 samples spiked of HIV, HCV, Treponema, SLE, and ANA. Cross-reactivity cannot be ruled out for CMV, Rubella, HAV, HCV, and HSV-1. No evidence for other cross-reactivity was observed. ### B. Interference #### Endogenous Interference The effect of the following endogenous substances and pharmaceutical compounds on assay performance was tested on the cobas analyzer. Interferences were tested up to the concentrations listed in Table 5. No significant interference with the assay was observed. Table 5. Endogenous Substances tested Concentrations | Interference Substance | Concentration tested | | --- | --- | | Bilirubin | 66 mg/dL | | Hemoglobin | 1000 mg/dL | | Intralipid | 2000 mg/dL | | Biotin | 1200 ng/mL | | Rheumatoid factors | 1200 IU/mL | | Human serum albumin | 7 g/dL | K260221 - Page 8 of 15 {8} | Cholesterol | 566 mg/dL | | --- | --- | ### Exogenous interference Testing was performed with 17 commonly used pharmaceuticals. Interferences were tested up to the concentrations listed in Table 6. No significant interference with the assay was found. In rare cases, interference caused by extremely high titers of antibodies to analyte-specific antibodies, streptavidin, or ruthenium can occur. These effects are minimized by suitable test design. Table 6. Exogenous Substances tested Concentrations | Active agent | Drug Conc [mg/L] | | --- | --- | | Acetylcystein | 150 | | Ampicillin-NA | 75.0 | | Ascorbic acid | 52.5 | | Cyclosporine | 1.80 | | Cefoxitin | 750 | | Heparin | 3300 IU/L | | Levodopa | 7.50 | | Methyldopa +1.5 | 22.5 | | Metronidazole | 123 | | Phenylbutazone | 321 | | Doxycyclin | 18.0 | | Acetylsalicylic acid | 30.0 | | Rifampicin | 48.0 | | Acetominophen | 156 | | Ibuprofen | 219 | | Theophylin | 60.0 | | Itraconazol | 50.0 | ### C. IgG Class Specificity An EBNA IgG class specificity study was performed by depleting EBV IgM with DTT treatment. The results showed no decreased signal with DTT treatment compared to untreated specimens demonstrating that the Elecsys EBV EBNA IgG assay selectively detects EBV EBNA antibodies. ### D. Hook Effect High positive samples were serially diluted to determine if high-dose hook effect was found with the Elecsys EBV EBNA IgG assay. No false negative result was observed. ### 4. Detection Limit (LoD): Not applicable ### 5. Stability, Expected Values (Controls, Calibrators, or Methods): K260221 - Page 9 of 15 {9} # A. Reagent Stability On-board reagent stability: Five samples covering negative, around the cut-off, moderately positive and high positive were tested with the Elecsys EBV EBNA IgG test on the cobas e 801 analyzer. The results showed that the reagent pack was stable on-board up to 16 weeks. Calibration stability: Five samples covering negative, around the cut-off, moderately positive and high positives were tested with the Elecsys EBV EBNA IgG test on cobas e 801 analyzer. The following stability results were obtained: - Lot calibration - up to 12 weeks - Calibration when using the same cobas e pack on the analyzer – up to 28 days. # B. Sample Stability A study was conducted to evaluate the effect of sample handling and storage conditions at room temperature (20 °C), refrigerated (2 - 8°C), and frozen (≤ -20°C). In addition, sample stability was evaluated after multiple freeze/thaw cycles. Sample stability studies support the following stability claims: | Storage Condition | Claimed Stability | | --- | --- | | Room Temp Storage (20-25 °C) | Up to 5 Days | | Refrigerated Storage (2-8 °C) | Up to 14 Days | | Frozen Storage (≤-20 °C) | Up to 3 Months | | Freeze/Thaw Cycles | No more than 3 cycles | # C. Fresh versus Frozen Sample Stability Study A study was conducted to demonstrate that the Elecsys EBV EBNA IgG detects EBNA IgG in both fresh and frozen samples. Fifty samples covering low negative, high negative, around the cut-off, and moderate positives were tested as fresh and after freezing at -20 °C on the Elecsys EBV EBNA IgG assay. The results demonstrated that EBV EBNA IgG levels were comparable in fresh and frozen samples. # 6. Assay Cut-Off: A study to establish the Elecsys EBV EBNA cut-off was performed using intended use samples. The estimated cut-off value for Elecsys EBV EBNA IgG is 1.0 COI. # B Comparison Studies: # 1. Method Comparison: Not applicable. See Section C - Clinical Studies K260221 - Page 10 of 15 {10} ## 2. Matrix Comparison: This study was conducted to determine whether the claimed matrices have equivalent performance on the Elecsys EBV EBNA IgG. The study evaluated 53 sets of matched samples collected in serum, lithium heparin, and EDTA plasma. The data supports comparable performance of samples collected in serum, lithium heparin, and EDTA plasma (Table 7). Table 7. Summary of results for regression analysis for different plasma types | Matrix Tested | N Sample Tested | Slope | Intercept | Range tested (COI) | | --- | --- | --- | --- | --- | | Li Heparin vs Serum | 53 | 0.917 | 0.000 | 0.041 – 244 | | K2 EDTA vs Serum | 53 | 0.992 | 0.000 | 0.041 – 259 | | K3 EDTA vs Serum | 53 | 0.976 | 0.000 | 0.040 – 253 | ## C Clinical Studies: ### 1. Clinical Study: A multisite study was conducted to evaluate clinical performance of the Elecsys EBV EBNA IgG on the cobas e 411 analyzer and to determine Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) with the predicate device. PPA and NPA to a composite consensus comparator were assessed using 974 specimens with routine laboratory requests for EBV testing. These specimens included 720 prospective samples not selected based on their routine EBV test results, and 253 retrospective samples selected based on their routine EBV test results to be presumed acute or presumed seronegative. Out of 720 prospective samples, 224 were from pediatric population. Out of 253 retrospective samples, 192 were from pediatric population. All specimens were tested with the Elecsys EBV IgM assay, the Elecsys EBV VCA IgG assay and the Elecsys EBV EBNA IgG assay (referred to as Elecsys EBV assay panel) and were also tested with 3 comparator FDA cleared EBV assay panels. Specimens were classified based on serological marker profile by the comparators. Table 8 presents the serological classification of the EBV disease status. Results for prospectively collected adults only and pediatrics are shown in Tables 9 and 10, respectively. Results for retrospectively collected adults only and pediatrics are shown in Tables 11 and 12, respectively. Prospective and retrospective percent agreement for Elecsys EBV EBNA IgG in relation to the EBV serological status and the composite comparator consensus EBV EBNA IgG results are shown in Table 13 and 14, respectively. Table 8. Result interpretation table used to determine the EBV serological status when using Elecsys EBV assays | | Elecsys EBV Assay Results | | | | --- | --- | --- | --- | | EBV Status | EBV IgM | EBV VCA IgG | EBV EBNA IgG | | EBV Seronegative | - | - | - | | Acute Infection | + | - | - | | | + | + | - | K260221 - Page 11 of 15 {11} | | Elecsys EBV Assay Results | | | | --- | --- | --- | --- | | EBV Status | EBV IgM | EBV VCA IgG | EBV EBNA IgG | | Past Infection | - | + | + | | | - | + | - | | Indeterminate EBV Status* | | | | | Isolated presence of EBNA IgG | - | - | + | | Past or Recovery or Reactivation | + | + | + | *For indeterminate and/or any additional combination of results not shown in this table, further diagnostic testing is recommended Table 9. PPA and NPA results of prospective population for adult cohort | Elecsys EBV EBNA IgG | Reference Method | | Total | | | --- | --- | --- | --- | --- | | | | Reactive | | Non-reactive | | | Reactive | 450 | 18 | 468 | | | Non-reactive | 0 | 28 | 29 | | Total | | 450 | 46 | 496 | | | | | | | | | | Estimate | 95% CI | | | PPA | | 100% | 99.2% - 100% | | | NPA | | 60.9% | 45.4% - 74.9% | | Table 10. PPA and NPA results of prospective population for pediatric cohort | Elecsys EBV EBNA IgG | Reference Method | | Total | | | --- | --- | --- | --- | --- | | | | Reactive | | Non-reactive | | | Reactive | 87 | 8 | 95 | | | Non-reactive | 2 | 127 | 129 | | Total | | 89 | 135 | 224 | | | | | | | | | | Estimate | 95% CI | | | PPA | | 97.8% | 92.1% - 99.7% | | | NPA | | 94.1% | 88.7% - 97.4% | | Table 11. PPA and NPA results of Retrospective adult cohort | Elecsys EBV EBNA IgG | Reference Method | | Total | | | --- | --- | --- | --- | --- | | | | Reactive | | Non-reactive | | | Reactive | 0 | 5 | 5 | | | Non-reactive | 0 | 56 | 56 | | Total | | 0 | 61 | 61 | | | | | | | | | | Estimate | 95% CI | | | PPA | | n/a | n/a | | | NPA | | 96.7% | 88.7% - 99.6% | | Table 12. PPA and NPA results of Retrospective pediatric cohort | Elecsys EBV EBNA IgG | Reference Method | | Total | | --- | --- | --- | --- | | | Reactive | Non-reactive | | K260221 - Page 12 of 15 {12} | | Reactive | 2 | 0 | 2 | | --- | --- | --- | --- | --- | | | Non-reactive | 1 | 189 | 190 | | Total | | 3 | 189 | 192 | | | | | | | | | | Estimate | 95% CI | | | PPA | | 66.7% | 9.4% - 99.2% | | | NPA | | 100.0% | 98.1% - 100.0% | | Table 13. Percent Agreement between Elecsys EBV EBNA IgG and Composite Comparator EBV EBNA IgG by EBV serological status in Prospective Samples (adults and pediatric) (n= 720) | EBV Serological Status (IgM / VCA IgG / EBNA IgG) | PPA Estimate and 95% CI | | | NPA Estimate and 95% CI | | | | --- | --- | --- | --- | --- | --- | --- | | | n/n | % | (95% CI) | n/n | % | (95% CI) | | Seronegative (-/-/-) | n/a | n/a | n/a | 129/134 | 96.3 | (91.5-98.8) | | Acute (+/-/-) | n/a | n/a | n/a | 6/6 | 100.0 | (54.1-100.0) | | Acute (+/+/−) | n/a | n/a | n/a | 8/9 | 88.9 | (51.8-99.7) | | Total Acute | n/a | n/a | n/a | 14/15 | 93.3 | (68.1-99.8) | | Past Infection (-/+/+) | 532/532 | 100.0% | (99.3-100.0%) | n/a | n/a | n/a | | Past Infection (-/+/−) | n/a | n/a | n/a | 12/32 | 37.5 | (21.1-56.3) | | Total Past Infection | 532/532 | 100.0% | (99.3-100.0%) | 12/32 | 37.5 | (21.1-56.3) | | Isolated Presence of EBNA IgG (-/-/+) | 3/4 | 75.0 | (19.4-99.4) | n/a | n/a | n/a | | Transient (+/+/+) | 2/3 | 66.7 | (9.4-99.2) | n/a | n/a | n/a | | Other Indeterminate (+/-/+) | n/a | n/a | n/a | n/a | n/a | n/a | | Total Indeterminate | 5/7 | 71.4 | (29.0-96.3) | n/a | n/a | n/a | | Overall | 537/539 | 99.6 | (98.7-100.0) | 155/181 | 85.6 | (79.7-90.4) | Table 14. Percent Agreement between Elecsys EBV EBNA IgG and Composite Comparator EBV EBNA IgG by EBV serological status in Retrospective Samples (adults and pediatric) (n= 253) | EBV Serological Status (IgM / VCA IgG / EBNA IgG) | PPA Estimate and 95% CI | | | NPA Estimate and 95% CI | | | | --- | --- | --- | --- | --- | --- | --- | | | n/n | % | (95% CI) | n/n | % | (95% CI) | | Seronegative (-/-/-) | n/a | n/a | n/a | 118/118 | 100.0% | (96.9-100.0%) | | Acute (+/-/-) | n/a | n/a | n/a | 47/47 | 100.0% | (92.5-100.0%) | | Acute (+/+/−) | n/a | n/a | n/a | 75/76 | 98.7 | (92.9-100.0) | | Total Acute | n/a | n/a | n/a | 122/123 | 99.2 | (95.6-100.0) | | Past Infection (-/+/+) | 2/2 | 100.0% | (15.8-100.0%) | n/a | n/a | n/a | K260221 - Page 13 of 15 {13} | Past Infection (-/+/−) | n/a | n/a | n/a | 8/9 | 88.9 | (51.8-99.7) | | --- | --- | --- | --- | --- | --- | --- | | Total Past Infection | 2/2 | 100.0% | (15.8-100.0%) | 8/9 | 88.9 | (51.8-99.7) | | Isolated Presence of EBNA IgG (-/-/+) | n/a | n/a | n/a | n/a | n/a | n/a | | Transient (+/+/+) | 0/1 | 0.0 | (0.0-97.5) | n/a | n/a | n/a | | Other Indeterminate (+/-/+) | n/a | n/a | n/a | n/a | n/a | n/a | | Total Indeterminate | 0/1 | 0.0 | (0.0-97.5) | n/a | n/a | n/a | | Overall | 2/3 | 66.7 | (9.4-99.2) | 248/250 | 99.2 | (97.1-99.9) | ## 2. Clinical Cut-Off See Section A8 ### D Expected Values/Reference Range: Table 15. Summary for Elecsys EBV EBNA IgG Results by Age Group and Sex | Age Group (Years) | Sex | Reactive | | Nonreactive | | Total | | --- | --- | --- | --- | --- | --- | --- | | | | n | % | n | % | n | | 2 to <6 years | Female | 1 | 5.3 | 18 | 94.7 | 19 | | | Male | 13 | 21.7 | 47 | 78.3 | 60 | | | Not Reported | 0 | 0.0 | 1 | 100.0 | 1 | | | Total | 14 | 17.5 | 66 | 82.5 | 80 | | 6 to <11 years | Female | 10 | 28.6 | 25 | 71.4 | 35 | | | Male | 13 | 25.5 | 38 | 74.5 | 51 | | | Total | 23 | 26.7 | 63 | 73.3 | 86 | | 11 to <16 years | Female | 15 | 28.3 | 38 | 71.7 | 53 | | | Male | 10 | 20.4 | 39 | 79.6 | 49 | | | Total | 25 | 24.5 | 77 | 75.5 | 102 | | 16 to <22 years | Female | 20 | 22.0 | 71 | 78.0 | 91 | | | Male | 15 | 26.3 | 42 | 73.7 | 57 | | | Total | 35 | 23.6 | 113 | 76.4 | 148 | | 22-39 years | Female | 71 | 71.7 | 28 | 28.3 | 99 | | | Male | 45 | 57.7 | 33 | 42.3 | 78 | | | Total | 116 | 65.5 | 61 | 34.5 | 177 | | 40-59 years | Female | 84 | 89.4 | 10 | 10.6 | 94 | | | Male | 102 | 94.4 | 6 | 5.6 | 108 | | | Total | 186 | 92.1 | 16 | 7.9 | 202 | | ≥60 years | Female | 67 | 91.8 | 6 | 8.2 | 73 | | | Male | 102 | 96.2 | 4 | 3.8 | 106 | | | Total | 169 | 94.4 | 10 | 5.6 | 179 | K260221 - Page 14 of 15 {14} | Total | Female | 268 | 57.8 | 196 | 42.2 | 464 | | --- | --- | --- | --- | --- | --- | --- | | | Male | 300 | 58.9 | 209 | 41.1 | 509 | | | Not Reported | 0 | 0.0 | 1 | 100.0 | 1 | | | Overall | 568 | 58.3 | 406 | 41.7 | 974 | ### E Other Supportive Instrument Performance Characteristics Data: Carryover Study: A carryover study was conducted. No carryover was detected. Electrical safety and electromagnetic compatibility (EMC) testing were performed, and the system was found to be acceptable. Software and cybersecurity documentation were acceptable. ### VIII Proposed Labeling: The labeling supports the finding of substantial equivalence for this device. ### IX Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. K260221 - Page 15 of 15