(36 days)
No
The summary describes a standard immunoassay using flow cytometry technology and does not mention any AI or ML components in the device description, intended use, or performance studies.
No.
This device is an in vitro diagnostic (IVD) test, specifically a multiplex flow immunoassay, intended for the qualitative detection of antibodies to aid in the laboratory diagnosis of infectious mononucleosis. It does not provide any form of therapy or treatment.
Yes
The device is intended for the "qualitative detection of two (2) separate analytes: Epstein-Barr Virus Viral Capsid Antigen (EBV VCA) IgM antibodies and Heterophile antibodies in human serum" and "can be used in conjunction with the BioPlex® 2200 EBV IgG kit as an aid in the laboratory diagnosis of infectious mononucleosis (IM)." This explicitly states its use in distinguishing a disease or condition, which defines a diagnostic device.
No
The device description clearly indicates it is a "multiplexed micro particle bead based immunoassay" and includes physical components like "serum based calibrators" and "vials of the BioPlex 2200 EBV IgM Positive Control and 2 vials of the BioPlex 2200 EBV IgM Negative Control." This is not a software-only device.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states it's for the "qualitative detection of two (2) separate analytes: Epstein-Barr Virus Viral Capsid Antigen (EBV VCA) IgM antibodies and Heterophile antibodies in human serum." This involves testing a sample taken from the human body (serum) in vitro (outside the body) to provide information about a person's health status (diagnosis of infectious mononucleosis).
- Device Description: The description details a "multiplexed micro particle bead based immunoassay" that uses "human serum" as the sample. This further confirms the in vitro nature of the testing.
- Clinical Laboratory Use: The intended user is the "clinical laboratory," which is a typical setting for IVD testing.
- Performance Studies: The document describes performance studies using "samples prospectively collected from individuals" and "retrospective positive samples," demonstrating that the device is used to analyze human specimens.
All of these points align with the definition of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
- l. Intended use(s):
The BioPlex® 2200 EBV IgM kit is a multiplex flow immunoassay intended for the qualitative detection of two (2) separate analytes: Epstein-Barr Virus Viral Capsid Antigen (EBV VCA) IgM antibodies and Heterophile antibodies in human serum. The test system can be used in conjunction with the BioPlex® 2200 EBV IgG kit as an aid in the laboratory diagnosis of infectious mononucleosis (IM).
The BioPlex® 2200 EBV IgM 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 IgM Calibrator Set
The BioPlex® 2200 EBV IgM Calibrator Set is intended for the calibration of the BioPlex® 2200 EBV IgM Reagent Pack.
BioPlex® 2200 EBV IgM Control Set
The BioPlex® 2200 EBV IgM Control Set is intended for use as an assayed quality control to monitor the overall performance of the BioPlex® 2200 Instrument and BioPlex® EBV IgM Reagent Pack in the clinical laboratory. The performance of the BioPlex® EBV IgM Control Set has not been established with any other EBV IgM antibody assays.
-
- Indication(s) for use:
Same as Intended Use
- Indication(s) for use:
Product codes (comma separated list FDA assigned to the subject device)
LJN, KTN, JIX, JJY
Device Description
The BioPlex 2200 EBV IgM kit is a multiplexed micro particle bead based immunoassay for the qualitative detection of IgM antibodies to EBV VCA GP125/p18 and Heterophile antigen in human serum using the Luminex flow cytometry technology. The BioPlex 2200 EBV IgM Calibrators set consists of two (2) distinct serum based calibrators. The BioPlex 2200 EBV IgM Control set consists of 2 vials of the BioPlex 2200 EBV IgM Positive Control and 2 vials of the BioPlex 2200 EBV IgM Negative Control. The positive controls are provided in a human serum matrix made from defibrinated plasma with added antibodies to EBV VCA GP125/p18 and Heterophile antigen derived from human disease state plasma. The negative controls are provided in a human serum matrix made from defibrinated plasma.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
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Input Imaging Modality
Not Found
Anatomical Site
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Indicated Patient Age Range
Assay performance characteristics have not been established for immunocompromised or immunosuppressed patients, cord blood, neonatal specimens, or infants.
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
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Description of the test set, sample size, data source, and annotation protocol
Performance of the modified BioPlex 2200 EBV IgM kit was tested against the cleared (predicate) BioPlex 2200 EBV IgM Kit using samples prospectively collected from individuals where an EBV IgM test was ordered (N=622).
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
1. Analytical performance:
a. Precision/Reproducibility:
A precision panel, consisting of nine (9) serum panel members for each analyte, was prepared by Bio-Rad Laboratories. For each analyte, two (2) panel members were high positive (2.5 to 4.0 AI), three (3) were low positive (1.4 to 2.0 AI), two (2) had antibody levels near the cutoff (0.7 to 1.3 AI), and two (2) were high negative (0.2 to 0.6 AI).
Precision testing was performed at Bio-Rad Laboratories on one lot of the modified BioPlex 2200 EBV IgM kit. Each of the nine (9) panel members was tested in duplicate on two (2) runs per days for ten (10) days for a total of 40 results per panel member (2 replicates x 2 runs x 10 days = 40 replicates per panel member). The data were analyzed for intra-assay and inter-assay precision in accordance to the CLSI EP5-A2 guideline. The standard deviation (SD) and percent coefficient of variation (%CV) were calculated. The results demonstrate that the performance of the modified device is substantially equivalent to the cleared device.
b. Linearity/assay reportable range: Not applicable
c. Traceability, Stability, Expected values (controls, calibrators, or methods):
No formulation changes have been made to the controls and calibrators. The control and calibrators are traceable against frozen internal standards which are anchored to the quantitation panel. The quantitation panel consists of patient samples whose analyte values span the assay range. The performance of the accelerated studies concluded that the modified EBV IgM reagent kit is equivalent to the current kit as all specifications were met.
d. Detection limit: Not applicable
e. Analytical specificity:
Testing for interfering substances was conducted according to CLSI EP7-A2. Samples were prepared by blending a pool of negative human serum with samples positive for EBV VCA IgM and Heterophile IgM to achieve values of 2.0 to 3.0 AI and interferent or solvent (negative control) was added exogenously at the levels indicated in the table. Test (containing interferent) and control samples were evaluated in replicates of ten using the modified BioPlex 2200 EBV IgM kit. The results demonstrated equivalence with the original (predicate) device. The percent change in signal ranged from -5.6% to 5.6% and -10.0% to 0.0% for the predicate and modified EBV VCA IgM assays, respectively, and -7.4% to 4.2% and -11.1% to 7.4% for the predicate and modified Heterophile IgM assays, respectively.
f. Assay cut-off:
The assay cut-off remains unchanged and the precision around the cut-off is equivalent to the original device.
2. Comparison studies:
a. Method comparison with predicate device:
Performance of the modified BioPlex 2200 EBV IgM kit was tested against the cleared (predicate) BioPlex 2200 EBV IgM Kit using samples prospectively collected from individuals where an EBV IgM test was ordered (N=622). The results of this analysis are presented and the conclusion of the assessment is that the performance of the device remains unchanged.
Method comparison was conducted following EP09. Linear regression analysis was performed using the results within the measuring range to compare the modified and predicate assays.
- VCA IgM: Slope = 0.9505, Intercept = 0.0474, Correlation (R2) = 0.9469
- Heterophile IgM: Slope = 1.0584, Intercept = -0.0076, Correlation (R2) = 0.9820
Prospectively Collected Samples (N=622):
VCA IgM:
- Positive Agreement: PPA=98.7%(78/79), 95% CI 93.2-99.8%
- Negative Agreement: NPA=98.7%(528/535), 95% CI 97.3-99.4%
Heterophile IgM:
- Positive Agreement: PPA= 100%(28/28), 95% CI 87.9-100%
- Negative Agreement: NPA= 100%(593/593), 95% CI 99.4-100%
Retrospective Positive Samples:
VCA IgM:
- Positive Agreement: PPA=100%(81/81), 95% CI 95.5 -100%
- Negative Agreement: NPA=N/A
Heterophile IgM:
- Positive Agreement: PPA=100%(81/81), 95% CI 95.5 -100%
- Negative Agreement: NPA=N/A
b. Matrix comparison: Not Applicable
3. Clinical studies:
a. Clinical Sensitivity: Not applicable
b. Clinical specificity: Not applicable
c. Other clinical supportive data: Refer to Method Comparison
4. Clinical cut-off: Refer to K062213
5. Expected values/Reference range:
The observed expected values for the modified BioPlex 2200 EBV IgM kit are presented in tables by age and gender for serum samples from individuals where EBV (N=622) and Heterophile (N=622) tests were ordered. The results from the modified device were equivalent to those from the predicate device.
Other Supportive Device and Instrument Information:
-
Design Control Activities Summary:
a. Risk Analysis: A Failure Mode and Effect Analysis (FMEA) method determined severity of consequences for a low signal pack (LSP) occurrence. RPN scores ranged from 6 for false positive results to 12 for false negative results for both EBV VCA IgM and Heterophile IgM Assays, indicating no additional mitigation activity required (below established threshold of ≤ 19).
b. Verification and Validation Activities: No incidence of LSP was observed in the assay formulation during initial development verification and clinical validation studies. Contamination studies showed the reformulated EBV IgM reagent kit, with protein stabilizer (goat) and protease inhibitor, provides adequate protection against bacteria and mold contamination, exhibiting only minimal signal loss within specifications. -
Accelerated Stability: Real time (2-8°C) and accelerated (25°C) stability studies were carried out on predicate and modified BioPlex 2200 EBV IgM kits. Results were within acceptable specifications, demonstrating the additives did not adversely impact stability. Performance was equivalent to the predicate kit.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
VCA IgM:
- Positive Percent Agreement (PPA) = 98.7% (78/79), 95% CI 93.2-99.8%
- Negative Percent Agreement (NPA) = 98.7% (528/535), 95% CI 97.3-99.4%
Heterophile IgM:
- Positive Percent Agreement (PPA) = 100% (28/28), 95% CI 87.9-100%
- Negative Percent Agreement (NPA) = 100% (593/593), 95% CI 99.4-100%
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 866.3235 Epstein-Barr virus serological reagents.
(a)
Identification. Epstein-Barr virus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to Epstein-Barr virus in serum. The identification aids in the diagnosis of Epstein-Barr virus infections and provides epidemiological information on diseases caused by these viruses. Epstein-Barr viruses are thought to cause infectious mononucleosis and have been associated with Burkitt's lymphoma (a tumor of the jaw in African children and young adults) and postnasal carcinoma (cancer).(b)
Classification. Class I (general controls).
0
BioPlex® 2200 EBV IgM 510(k) Summary
Bio-Rad Laboratories hereby submits this 510(k) in accordance with the requirements of SMDA 1990 and 21 CFR 807.92. This summary of 510(k) safety and effectiveness information provides detail as a basis for a determination of substantial equivalence for the BioPlex® 2200 EBV IgM kit.
510(k) Number:
Summary Preparation Date:
October 30, 2012
Applicant:
Bio-Rad Laboratories
Contact:
Juang Wang Regulatory Affairs Representative
Purpose for Submission:
Modification to cleared device (K062213), see section Substantial Equivalence Information for a description of the changes.
Measurand:
Epstein-Barr Virus Viral Capsid Antigen (EBV VCA) IgM antibodies to VCA glycoprotein (GP125/p18) and Heterophile antibodies
Type of Test:
Multiplexed micro particle immunoassay based on Luminex technology
Proprietary and Established Names:
BioPlex® 2200 EBV IgM Kit
BioPlex® 2200 EBV IgM Calibrator Set
BioPlex® 2200 EBV IgM Control Set
NOV 2 2012
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| Product Code | Classification | Regulation Section | Panel |
|---|---|---|---|
| Antibody IgM, if, | |||
| Epstein-Barr virus | |||
| (LJN) | Class I | 21 CFR § 866.3235, | |
| Epstein-Barr virus | |||
| serological reagents | Microbiology (83) | ||
| System, Test, Infectious | |||
| Mononucleosis | |||
| (KTN) | Class II | 21 CFR § 866.5640, | |
| Infectious mononucleosis | |||
| immunological test system | Immunology (82) | ||
| Calibrator, Multi-Analyte | |||
| Mixture | |||
| (JIX) | Class II | 21 CFR § 862.1150 – | |
| Calibrator | Clinical Chemistry | ||
| (75) | |||
| Multi-Analyte Controls | |||
| All kinds(assayed) | |||
| (JJY) | Class I | 21 CFR § 862.1660 – | |
| Quality Control Material | |||
| (Assayed and Unassayed) | Clinical Chemistry | ||
| (75) |
Regulatory Information:
Intended Use:
- l. Intended use(s):
The BioPlex® 2200 EBV IgM kit is a multiplex flow immunoassay intended for the qualitative detection of two (2) separate analytes: Epstein-Barr Virus Viral Capsid Antigen (EBV VCA) IgM antibodies and Heterophile antibodies in human serum. The test system can be used in conjunction with the BioPlex® 2200 EBV IgG kit as an aid in the laboratory diagnosis of infectious mononucleosis (IM).
The BioPlex® 2200 EBV IgM 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 IgM Calibrator Set
The BioPlex® 2200 EBV IgM Calibrator Set is intended for the calibration of the BioPlex® 2200 EBV IgM Reagent Pack.
BioPlex® 2200 EBV IgM Control Set
The BioPlex® 2200 EBV IgM Control Set is intended for use as an assayed quality control to monitor the overall performance of the BioPlex® 2200 Instrument and BioPlex® EBV IgM Reagent Pack in the clinical laboratory. The performance of the BioPlex® EBV IgM Control Set has not been established with any other EBV IgM antibody assays.
-
- Indication(s) for use:
2
Same as Intended Use
-
- Special conditions for use statement(s): For prescription use only
-
- Special instrument requirements: Bio-Rad BioPlex® 2200 System
Device Description:
The BioPlex 2200 EBV IgM kit is a multiplexed micro particle bead based immunoassay for the qualitative detection of IgM antibodies to EBV VCA GP125/p18 and Heterophile antigen in human serum using the Luminex flow cytometry technology. The BioPlex 2200 EBV IgM Calibrators set consists of two (2) distinct serum based calibrators. The BioPlex 2200 EBV IgM Control set consists of 2 vials of the BioPlex 2200 EBV IgM Positive Control and 2 vials of the BioPlex 2200 EBV IgM Negative Control. The positive controls are provided in a human serum matrix made from defibrinated plasma with added antibodies to EBV VCA GP125/p18 and Heterophile antigen derived from human disease state plasma. The negative controls are provided in a human serum matrix made from defibrinated plasma.
Substantial Equivalence Information:
-
- Predicate device name(s): BioPlex 2200 EBV IgM Kit
-
- Predicate 510(k) number(s): K062213
-
- Comparison with predicate:
| Item | Device | Predicate |
|---|---|---|
| Intended Use | The BioPlex® 2200 EBV IgM kit is | |
| a multiplex flow immunoassay | ||
| intended for the qualitative | ||
| detection of two (2) separate | ||
| analytes; Epstein-Barr Virus Viral | ||
| Capsid Antigen (EBV VCA) IgM | ||
| antibodies and Heterophile | ||
| antibodies in human serum. The test | ||
| system can be used in conjunction | ||
| with the BioPlex® 2200 EBV IgG | ||
| kit as an aid in the laboratory | ||
| diagnosis of infectious | ||
| mononucleosis (IM). | same |
3
| Similarities | ||
|---|---|---|
| Item | Device | Predicate |
| The BioPlex 2200 EBV IgM 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. | ||
| Matrix | Serum | same |
| Antigen | Recombinant protein to EBV VCA | |
| GP125/p18 (40kD), and Heterophile | ||
| antigen (horse erythrocyte stromal | ||
| extract) | same | |
| Technology | Multiplexed microparticle flow | |
| cytometry immunoassay | same |
| Differences | ||||||
|---|---|---|---|---|---|---|
| Item | Device | Predicate | ||||
| QC procedure | QC once per day and per new | |||||
| reagent pack lot | QC once per pack | |||||
| and per day | ||||||
| Bead Reagent | 2 mg/mL protein stabilizer (goat) | |||||
| and protease inhibitor in particle | ||||||
| (bead) diluent | None | |||||
| Software Version | Version 2.2/4.0 | Version 1.1/1.2 |
Standard/Guidance Document Referenced (if applicable):
-
- CLSI EP05-A2 Evaluation of precision performance of quantitative measurement methods
-
- CLSI EP07-A2 Interference testing in clinical chemistry
4
-
- CLSI EP09-A2 Method comparison and bias estimation using patient samples (This is used for Method Comparison studies)
-
- CLSI EP12-A2-User protocol for evaluation of qualitative test performance
-
- EN 1360:200 Stability testing of In Vitro Diagnostic Reagents
Test Principle:
- The BioPlex 2200 EBV IgM kit is an automated system and uses the following procedure.
The kit contains two different populations of dyed beads: one population is coated with EBV VCA glycoprotein (GP125/p18) and the other is coated with Heterophile antigens. 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, anti-human IgM antibody, 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 resuspended 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 to the reaction vessel and the absence of significant non-specific binding in serum.
The instrument is calibrated using a set of two (2) distinct calibrator vials, supplied separately by Bio-Rad Laboratories. The two (2) vials representing two (2) different antibody concentrations are used for calibration. The result for each of these antibodies is expressed as an antibody index (AI).
Performance Characteristics (if/when applicable):
-
- Analytical performance:
- a. Precision/Reproducibility:
A precision panel, consisting of nine (9) serum panel members for each analyte, was prepared by Bio-Rad Laboratories. For each analyte, two (2) panel members were high positive (2.5 to 4.0 AI), three (3) were low positive (1.4 to 2.0 AI), two (2) had antibody levels near the cutoff (0.7 to 1.3 AI), and two (2) were high negative (0.2 to 0.6 AI).
Precision testing was performed at Bio-Rad Laboratories on one lot of the
5
modified BioPlex 2200 EBV IgM kit. Each of the nine (9) panel members was tested in duplicate on two (2) runs per days for ten (10) days for a total of 40 results per panel member (2 replicates x 2 runs x 10 days = 40 replicates per panel member). The data were analyzed for intra-assay and inter-assay precision in accordance to the CLSI EP5-A2 guideline. The standard deviation (SD) and percent coefficient of variation (%CV) were calculated. The results of the precision testing and comparison between the modified device and the cleared device are shown below. The results demonstrate that the performance of the modified device is substantially equivalent to the cleared device. For the precision and reproducibility information of the BioPlex 2200 EBV IgM kit please refer to the decision summary of K062213.
| VCA IgM | Mean (AI) | | Within Run %CV | | | Between Run %CV | Between Day %CV | | Total Precision
%CV | |
|------------------|-----------|----------|----------------|----------|-----------|-----------------|-----------------|----------|------------------------|----------|
| Panel
Members | Predicate | Modified | Predicate | Modified | Predicate | Modified | Predicate | Modified | Predicate | Modified |
| High Negative | 0.4 | 0.4 | 8.8% | 5.6% | 0.0% | 0.0% | 2.9% | 0.0% | 9.3% | 5.6% |
| High Negative | 0.5 | 0.5 | 8.4% | 7.7% | 3.2% | 0.0% | 0.0% | 4.6% | 8.9% | 9.0% |
| Near Cutoff | 0.9 | 0.9 | 4.3% | 6.1% | 3.0% | 0.0% | 0.0% | 2.1% | 5.3% | 6.4% |
| Near Cutoff | 1.2 | l . l | 4.4% | 7.7% | 2.6% | 0.0% | 2.9% | 0.0% | રું છે.જેન્દ્ર | 7.7% |
| Low Positive | 1.5 | 1 .3 | 4.9% | 4.7% | 0.0% | 0.0% | 2.3% | 1.9% | 5.4% | 5.1% |
| Low Positive | 1.9 | 1 .6 | 7.0% | 7.4% | 2.4% | 3.3% | 0.0% | 0.0% | 7.3% | 8.1% |
| Low Positive | 2.1 | 1.9 | 5.3% | 6.6% | 1.3% | 2.2% | 1.9% | 3.1% | 5.8% | 7.6% |
| High Positive | 3.2 | 2.9 | 4.4% | 4.5% | 0.0% | 0.5% | 1.2% | 0.0% | 4.5% | 4.5% |
| High Positive | 3.8 | 3.8 | 2.3% | 2.2% | 2.0% | 1.6% | 0.6% | 0.0% | 3.1% | 2.7% |
VCA IgM Precision Comparison Summary: Modified vs. Predicate devices
Heterophile IgM Precision Comparison Summary: Modified vs. Predicate devices
| Heterophile
IgM | Mean (AI) | | Within Run %CV | | Between Run %CV | | Between Day %CV | | Total Precision
%CV | |
|--------------------|-----------|----------|----------------|----------|-----------------|----------|-----------------|----------|------------------------|----------|
| Panel
Members | Predicate | Modified | Predicate | Modified | Predicate | Modified | Predicate | Modified | Predicate | Modified |
| High Negative | 0.6 | 0.6 | 5.3% | 6.5% | 0.0% | 0.0% | 0.0% | 4.5% | 5.3% | 7.9% |
| High Negative | 0.6 | 0.6 | 6.5% | 7.0% | 0.0% | 0.0% | 4.4% | 4.7% | 7.8% | 8.4% |
| Near Cutoff | 0.8 | 0.8 | 5.6% | 6.8% | 2.0% | 0.0% | 2.5% | 1.8% | 6.4% | 7.1% |
| Near Cutoff | 0.8 | 0.8 | 5.6% | 5.6% | 4.0% | 0.0% | 0.0% | 4.2% | 6.8% | 7.0% |
| Low Positive | 1.6 | 1.6 | 3.8% | 4.9% | 3.8% | 0.0% | 0.0% | 2.1% | 5.4% | 5.4% |
| Low Positive | । 'ર્ણ | 1.6 | 4.3% | 5.3% | 0.0% | 0.0% | 2.5% | 2.8% | 5.0% | 6.0% |
| Low Positive | 2.3 | 2.2 | 4.9% | 5.2% | 1.0% | 1.8% | 0.0% | 2.1% | 5.0% | 5.9% |
| High Positive | 2.7 | 2.6 | 3.1% | 4.1% | 1.2% | 2.4% | 1.4% | 2.3% | 3.6% | 5.3% |
| High Negative | 3.1 | 3.0 | 3.5% | 4.6% | -2.7% | 0.0% | 0.0% | 2.1% | 4.4% | 5.1% |
b. Linearity/assay reportable range: Not applicable
б
6
- Traceability, Stability, Expected values (controls, calibrators, or methods): C. No formulation changes have been made to the controls and calibrators. The control and calibrators are traceable against frozen internal standards which are anchored to the quantitation panel. The quantitation panel consists of patient samples whose analyte values span the assay range. The performance of the accelerated studies concluded that the modified EBV IgM reagent kit is equivalent to the current kit as all specifications were met.
- d. Detection limit: Not applicable
- e. Analytical specificity:
Testing for interfering substances was conducted according to CLSI EP7-A2. Samples were prepared by blending a pool of negative human serum with samples positive for EBV VCA IgM and Heterophile IgM to achieve values of 2.0 to 3.0 AI and interferent or solvent (negative control) was added exogenously at the levels indicated in the table below. Test (containing interferent) and control samples were evaluated in replicates of ten using the modified BioPlex 2200 EBV IgM kit. The results demonstrated equivalence with the original (predicate) device. The percent change in signal ranged from -5.6% to 5.6% and -10.0% to 0.0% for the predicate and modified EBV VCA IgM assays, respectively, and -7.4% to 4.2% and -11.1% to 7.4% for the predicate and modified Heterophile IgM assays, respectively. For information on testing for interfering substances with the predicate BioPlex 2200 EBV IgM kit please refer to the decision summary for K062213.
| Substance | Concentration |
|---|---|
| Hemoglobin | 500 mg/dL |
| Bilirubin | |
| (unconjugated) | 20 mg/dL |
| Bilirubin (conjugated) | 30 mg/dL |
| Cholesterol | 500 mg/dL |
| Red Blood Cells | 0.4% (v/v) |
| Gamma-Globulin | 6 g/dL |
| Triglycerides | 3300 mg/dL |
| Total Protein | |
| (albumin) | 12 g/dL |
| Beta-Carotene | 0.6 mg/dL |
| Ascorbic Acid | 3 mg/dL |
Interference Substances
f. Assay cut-off:
The assay cut-off remains unchanged and the precision around the cut-off is
7
equivalent to the original device (see K062213).
2. Comparison studies:
- Method comparison with predicate device: a.
Performance of the modified BioPlex 2200 EBV IgM kit was tested against the cleared (predicate) BioPlex 2200 EBV IgM Kit using samples prospectively collected from individuals where an EBV IgM test was ordered (N=622). The results of this analysis are presented below and the conclusion of the assessment is that the performance of the device remains unchanged. For the assay performance of the BioPlex EBV IgM kit versus other commercially available IgM EIA kits please refer to K062213.
Prospectively Collected Samples
Method comparison was conducted following EP09. Linear regression analysis was performed using the results within the measuring range to compare the modified and predicate assays. The regression parameters (slope, intercept, and correlation (R2)) and scatter plots of the modified device versus the predicate device are presented below.
Statistics of regression analysis
| BioPlex EBV IgM Assay | Slope | Intercept | Correlation (R2) |
|---|---|---|---|
| VCA IgM | 0.9505 | 0.0474 | 0.9469 |
| Heterophile IgM | 1.0584 | -0.0076 | 0.9820 |
Image /page/7/Figure/8 description: The image contains two scatter plots comparing test results versus control results. The left plot, titled "VCA IgM (8) Method Comparison Test vs. Control (n=214)", shows a linear relationship with the equation y = 0.9505x + 0.0474 and an R-squared value of 0.9469. The right plot, titled "Heterophile IgM (52) Method Comparison Test vs. Control (n=31)", also shows a linear relationship with the equation y = 1.0584x - 0.0076 and an R-squared value of 0.982.
Individuals With a VCA IgM Test Ordered: Modified BioPlex 2200 EBV IgM versus Cleared BioPlex 2200 EBV IgM
| Predicate(BioPlex 2200 VCA IgM results) | ||||||
|---|---|---|---|---|---|---|
| Modified | ||||||
| BioPlex | ||||||
| 2200 VCA | ||||||
| IgM | Positive | Equivocal | Negative | Total | %Agreement | |
| Positive | 78 | 5 | 0 | 83 | PPA=98.7%(78/79), | |
| 95% CI 93.2-99.8% | ||||||
| Equivocal | 1 | 8 | 2 | 11 |
8
| Negative | 0 | 0 | 528 | 528 | NPA=98.7%(528/535)
95% CI 97.3-99.4% |
|----------|----|----|-----|-----|-----------------------------------------|
| Total | 79 | 13 | 530 | 622 | |
Individuals With a Heterophile IgM Test Ordered:
Modified BioPlex 2200 EBV IgM versus cleared BioPlex 2200 EBV IgM
| Predicate(BioPlex 2200 Heterophile IgM results) | ||||||
|---|---|---|---|---|---|---|
| Modified | ||||||
| BioPlex | ||||||
| 2200 | ||||||
| Heterophile | ||||||
| IgM | Positive | Equivocal | Negative | Total | %Agreement | |
| Positive | 28 | 0 | 0 | 28 | PPA= $100%(28/28)$ , | |
| $95%$ CI 87.9-100% | ||||||
| Equivocal | 0 | 1 | 0 | 1 | ||
| Negative | 0 | 0 | 593 | 593 | NPA= $100%(593/593)$ , | |
| $95%$ CI 99.4-100% | ||||||
| Total | 28 | 1 | 593 | 622 |
Retrospective Positive Samples
The purpose of this study was to demonstrate that the test results of retrospective positive samples between the current marketed device (Predicate, K062213) and the modified device are equivalent for the BioPlex 2200 EBV IgM assay. The testing was performed using the samples from individuals who were presumptively positive for either VCA IgM or Heterophile IgM. Results are shown below.
| Predicate(BioPlex 2200 VCA IgM results) | ||||||
|---|---|---|---|---|---|---|
| BioPlex | Positive | Equivocal Negative Total | %Agreement | |||
| 2200 VCA | Positive | 81 | 0 | 0 | 81 | PPA=100%(81/81). |
| IgM | 95% CI 95.5 -100% | |||||
| Equivocal 0 | 0 | () | 0 | |||
| Negative | 0 | 0 | 0 | NPA=N/A | ||
| Total | 81 | 0 | 81 | |||
| Predicate(BioPlex 2200 Heterophile IgM results) | ||||||
|---|---|---|---|---|---|---|
| Positive | Equivocal | Negative | Total | %Agreement | ||
| BioPlex | ||||||
| 2200 | ||||||
| Heterophile | ||||||
| IgM | Positive | 81 | 0 | 0 | 81 | PPA=100%(81/81), |
| 95% CI 95.5 -100% | ||||||
| Equivocal | 0 | 0 | 0 | 0 | ||
| Negative | 0 | 0 | 0 | 0 | NPA=N/A | |
| Total | 81 | 0 | 0 | 81 |
b. Matrix comparison:
9
Not Applicable
-
- Clinical studies:
- a. Clinical Sensitivity:
Not applicable
-
b. Clinical specificity:
Not applicable -
c. Other clinical supportive data (when a. and b. are not applicable):
Refer to Method Comparison -
- Clinical cut-off: Refer to K062213
-
- Expected values/Reference range:
The observed expected values for the modified BioPlex 2200 EBV IgM kit are presented in the tables below by age and gender for serum samples from individuals where EBV (N=622) and Heterophile (N=622) tests were ordered. The results from the modified device were equivalent to those from the predicate device. For the expected values and positive and negative predictive values for the intended use populations obtained previously with the predicate BioPlex 2200 EBV IgM kit, please refer to the decision summary of K062213.
| Modified BioPlex 2200 VCA IgM | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Age in | |||||||||
| Years | Gender | Positive | Equivocal | Negative | Total | ||||
| N | % | N | % | N | % | N | |||