(299 days)
No
The device description and performance studies focus on traditional immunoassay methodology and statistical analysis of results, with no mention of AI or ML algorithms for data processing, interpretation, or decision-making.
No.
This device is an in vitro diagnostic (IVD) kit designed for the qualitative detection of IgG antibodies to Measles, Mumps, Rubella, and Varicella-zoster virus (VZV) to aid in the determination of serological status, not to treat or prevent disease.
Yes
The "Intended Use" section states that the kit is "intended as an aid in the determination of serological status to Measles, Mumps, Rubella, and VZV," which indicates it is used to help diagnose or assess a patient's condition.
No
The device is a kit that uses physical reagents (dyed beads, antigens, antibodies) and requires a specific hardware system (Bio-Rad BioPlex 2200 System) to perform the assay. It is not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states that the kit is "intended for the qualitative detection of IgG antibodies to Measles, Mumps, Rubella, and Varicella-zoster virus (VZV) in human serum and EDTA or heparinized plasma." This describes a test performed in vitro (outside the body) on a human specimen (serum and plasma) to provide information about a person's health status (presence of antibodies).
- Device Description: The description details a laboratory-based assay using reagents, beads, and an instrument to analyze patient samples. This is characteristic of an in vitro diagnostic device.
- Performance Studies: The document describes performance studies conducted using human serum samples, comparing the device's results to other commercially available immunoassays. This is a standard process for evaluating the performance of IVDs.
- Predicate Devices: The mention of "Predicate Device(s)" which are other commercially available IVDs (like EIAs) further confirms that this device falls into the same category.
The definition of an In Vitro Diagnostic (IVD) is a medical device that is used to perform tests on samples such as blood, urine, or tissues to detect diseases or other conditions. This device clearly fits that definition.
N/A
Intended Use / Indications for Use
The BioPlex™ 2200 MMRV IgG kit is a multiplex flow immunoassay intended for the qualitative detection of IgG antibodies to Measles, Mumps, Rubella, and Varicella-zoster virus (VZV) in human serum and EDTA or heparinized plasma. The BioPlex 2200 MMRV IgG kit is intended for use with the Bio-Rad BioPlex 2200 System.
This kit is intended as an aid in the determination of serological status to Measles, Mumps, Rubella, and VZV. This kit is not intended for use in screening blood or plasma donors.
The performance of this assay has not been established for use in neonates, pediatrics and immunocompromised patients, or for use at point of care facilities.
Product codes
OPL, LJB, LJB, LJY, LFY
Device Description
The BioPlex 2200 MMRV IgG kit uses multiplex flow immunoassay, a methodology that greatly resembles traditional EIA, but permits simultaneous detection and identification of many antibodies in a single tube. Four (4) different populations of dyed beads are coated with antigens to identify the presence of IgG class antibodies associated with Measles, Mumps, Rubella and Varicella-zoster. The BioPlex 2200 System combines an aliquot of patient sample, sample diluent, and bead set reagent into a reaction vessel. The mixture is incubated at 37°C. After a wash cycle, anti-human IgG 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 three (3) distinct calibrator vials, supplied separately by Bio-Rad Laboratories.
Mentions image processing
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Mentions AI, DNN, or ML
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Input Imaging Modality
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Anatomical Site
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Indicated Patient Age Range
The performance of this assay has not been established for use in neonates, pediatrics and immunocompromised patients, or for use at point of care facilities.
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
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Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
A. Expected Values
The prevalence and expected values for each of the MMRV IgG assays were determined in a prospective study using serum samples from pregnant women (N = 396); and serum samples with a Measles, Mumps, Rubella, or VZV IgG test ordered for routine testing. The routine testing population included samples from pre-employment screening (N=393) and samples from subjects with a Measles test ordered (N=197), Mumps test ordered (N=199), Rubella test ordered (N=199), or VZV Test ordered (N=195).
B. Reproducibility Studies
To assess reproducibility of each of the assays in the BioPlex 2200 MMRV IgG kit, a reproducibility panel was prepared at Bio-Rad Laboratories. The positive panel members were prepared by combining one or more antibody positive patient samples in 3 different matrices (serum, EDTA plasma, and sodium heparin plasma) with one or more of the 4 analytes contained in the BioPlex 2200 MMRV IgG (Measles, Mumps, Rubella, and VZV). The panel contained members with varying levels of antibodies to the analytes in the BioPlex 2200 MMRV IgG kit, and a positive control (antibody positive for all analytes). Reproducibility testing was performed at 3 U.S. clinical trial sites. Three lots of BioPlex 2200 MMRV IgG Reagent Packs, 3 lots of BioPlex 2200 MMRV IgG Calibrator Set and 3 lots of BioPlex 2200 MMRV IgG Control Set were used to evaluate reproducibility. Each site evaluated 1 lot of the BioPlex 2200 MMRV IgG kit. Each of the panel members and a positive and negative control was tested in quadruplicate on 1 run per day over 5 days at each of 3 sites (4 replicates x 1 run x 5 days = 20 replicates per panel member per site = 60 total replicates for 3 sites). The data were analyzed for intra-assay and inter-assay reproducibility according to the Clinical and Laboratory Standards Institute (CLSI) guidance EP15-A2 (Vol. 25, No. 17). The mean Antibody Index (AI), standard deviation (SD), and percent coefficient of variation (%CV) for each panel member were calculated.
C. Comparative Testing
Comparative Testing: Prospective
Performance of the MMRV IgG kit was evaluated against corresponding commercially available Measles, Mumps, Rubella, and VZV immunoassays. Serum samples from pregnant women (N = 396) and serum samples with a Measles, Mumps, Rubella, or VZV IgG test ordered (N = 1183) were tested at 3 U.S. clinical trial sites. Serum samples with a Measles, Mumps, Rubella, or VZV IgG test ordered included serum samples submitted for routine testing (N = 790) and serum samples for pre-employment evaluation (N = 393). Equivocal results obtained for Mumps and Measles on the commercially available ElAs were further tested on two additional commercially available EIAs for consensus. Equivocal results obtained for Rubella on the commercially available EIA were re-tested on the commercially available EIA, following the manufacturer's recommendations.
Comparative Testing: Retrospective
Performance of the MMRV IgG kit was evaluated against corresponding commercially available Measles, Mumps, Rubella, and VZV immunoassays using retrospective serum samples negative for antibodies to Measles (N = 93), Mumps (N = 96), Rubella (N = 268), or VZV (N = 143). The negative samples for Measles and Mumps were selected using a consensus of two out of three commercially available EIAs. Negative samples for Rubella and VZV were selected using the respective commercially available ElAs used for the comparative analysis.
Correlation with CDC Rubella Evaluation Serum Panel
The performance of the BioPlex 2200 MMRV IgG kit was assessed using a masked, characterized Rubella IgG serum panel from the CDC. The panel consisted of 82 positive samples and 18 negative samples (N=100 total).
Correlation of the BioPlex 2200 MMRV IgG Rubella IgG Assay with the WHO Standard
Dilutions of the WHO anti-Rubella immunoglobulin, 1st International Standard, RUBI-1-94, in the range of 0 - 20 IU/ml, were analyzed with the BioPlex 2200 Rubella IgG assay.
CDC Rubella Low Positive Control Testing
A lyophilized CDC low positive control serum was prepared by and tested at one clinical trial site. The control was tested neat and dilution was run in duplicate. (N=2 samples).
D. Cross-Reactivity
A cross-reactivity study was performed to determine if samples from various disease states and other potentially cross-reacting agents interfere with test results when tested with the BioPlex 2200 MMRV IgG kit. Samples known to be positive for one of the thirteen potential crossreactants listed in the table below were evaluated with the BioPlex 2200 MMRV IgG assays. Due to the high prevalence of IgG antibodies to Measles, Mumps, Rubella, and VZV in the population, and in order to properly evaluate the potential cross-reactivity, all samples were pre-tested by commercially available Measles, Mumps, Rubella and VZV assays and only those that tested negative by the commercially available assay were further tested by the BioPlex 2200 MMRV IgG kit.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Expected Values
Pregnant Women (N = 396)
- Measles IgG: Pos 91.4%, Eqv 2.3%, Neg 6.3%
- Mumps IgG: Pos 88.1%, Eqv 2.8%, Neg 9.1%
- Rubella IgG: Pos 93.9%, Eqv 2.0%, Neg 4.0%
- VZV IgG: Pos 87.9%, Eqv 2.0%, Neg 10.1%
Measles, Mumps, Rubella, or VZV Test Ordered (N = 590 to 592 depending on assay)
- Measles IgG: Pos 90.0%, Eqv 2.7%, Neg 7.3%
- Mumps IgG: Pos 88.5%, Eqv 3.7%, Neg 7.8%
- Rubella IgG: Pos 87.5%, Eqv 3.4%, Neg 9.1%
- VZV IgG: Pos 89.5%, Eqv 2.0%, Neg 8.5%
Comparative Testing
Pregnant Women (N = 396)
- Measles IgG: Pos % Agreement 93.3% (362/388), Neg % Agreement 100% (8/8)
- 95% CI Pos: 90.4 - 95.4%
- 95% CI Neg: 67.5 - 100%
- Mumps IgG: Pos % Agreement 94.3% (349/370), Neg % Agreement 96.2% (25/26)
- 95% CI Pos: 91.5 - 96.3%
- 95% CI Neg: 81.1 - 99.3%
- Rubella IgG: Pos % Agreement 97.9% (369/377), Neg % Agreement 73.7% (14/19)
- 95% CI Pos: 95.9 - 98.9%
- 95% CI Neg: 51.2 - 88.2%
- VZV IgG: Pos % Agreement 95.1% (348/366), Neg % Agreement 100% (30/30)
- 95% CI Pos: 92.4 - 96.9%
- 95% CI Neg: 88.6 - 100%
Test Ordered Samples (N = 1183)
- Measles IgG: Pos % Agreement 94.7% (1042/1100), Neg % Agreement 80.2% (65/81)
- 95% CI Pos: 93.2 - 95.9%
- 95% CI Neg: 70.3 - 87.5%
- Mumps IgG: Pos % Agreement 90.4% (1006/1113), Neg % Agreement 91.0% (61/67)
- 95% CI Pos: 88.5 - 92.0%
- 95% CI Neg: 81.8 - 95.8%
- Rubella IgG: Pos % Agreement 94.8% (1060/1118), Neg % Agreement 86.2% (56/65)
- 95% CI Pos: 93.3 - 96.0%
- 95% CI Neg: 75.7 - 92.5%
- VZV IgG: Pos % Agreement 94.0% (1047/1114), Neg % Agreement 98.4% (60/61)
- 95% CI Pos: 92.4 - 95.2%
- 95% CI Neg: 91.3 - 99.7%
Retrospective Negative Samples
- Measles IgG (N = 93): Neg % Agreement 100% (93/93)
- 95% CI: 96.0 - 100%
- Mumps IgG (N = 96): Pos 6, Neg % Agreement 100% (83/83)
- 95% CI: 95.6 - 100%
- Rubella IgG (N = 268): Pos 3, Eqv 8, Neg % Agreement 95.9% (257/268)
- 95% CI: 92.8 - 97.7%
- VZV IgG (N = 143): Neg % Agreement 100% (143/143)
- 95% CI: 97.4 - 100%
Correlation with CDC Rubella Evaluation Serum Panel (N = 100)
- Rubella IgG: Reference Positive 82 (BioPlex 2200 Pos 81, BioPlex 2200 Neg 1), Reference Negative 18 (BioPlex 2200 Neg 18)
Cross-Reactivity
Negative Agreement for various cross-reactants ranged from 100% (e.g., CMV IgG, EBV VCA IgG) to some cases where assessment was limited by sample size for HCV Ab and ANA IgG.
Predicate Device(s)
BioMerieux VIDAS Measles IgG (MSG), BioMerieux VIDAS Mumps IgG (MPG), K961053, K923122
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
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§ 866.3510 Rubella virus serological reagents.
(a)
Identification. Rubella virus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to rubella virus in serum. The identification aids in the diagnosis of rubella (German measles) or confirmation of a person's immune status from past infections or immunizations and provides epidemiological information on German measles. Newborns infected in the uterus with rubella virus may be born with multiple congenital defects (rubella syndrome).(b)
Classification. Class II. The special controls for this device are:(1) National Committee for Clinical Laboratory Standards':
(i) 1/LA6 “Detection and Quantitation of Rubella IgG Antibody: Evaluation and Performance Criteria for Multiple Component Test Products, Speciment Handling, and Use of the Test Products in the Clinical Laboratory, October 1997,”
(ii) 1/LA18 “Specifications for Immunological Testing for Infectious Diseases, December 1994,”
(iii) D13 “Agglutination Characteristics, Methodology, Limitations, and Clinical Validation, October 1993,”
(iv) EP5 “Evaluation of Precision Performance of Clinical Chemistry Devices, February 1999,” and
(v) EP10 “Preliminary Evaluation of the Linearity of Quantitive Clinical Laboratory Methods, May 1998,”
(2) Centers for Disease Control's:
(i) Low Titer Rubella Standard,
(ii) Reference Panel of Well Characterized Rubella Sera, and
(3) World Health Organization's International Rubella Standard.
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BIOPLEX 2200 MMRV IgG 510(k) SUMMARY
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807 92.
| 510(k) Number | 510(k) Summary Report Date |
|---|---|
| K091616 | March 25, 2010 |
MANUFACTURER INFORMATION
| Manufacturer | |
|---|---|
| Manufacturer Address | Bio-Rad Laboratories, Inc. |
| Clinical Systems Division | |
| 4000 Alfred Nobel Drive | |
| Hercules, CA 94547 | |
| Telephone | (510) 724-7000 |
| Establishment Registration No. | 2915274 |
| Owner / Operator | Bio-Rad Laboratories, Inc. |
| 4000 Alfred Nobel Drive | |
| Hercules, CA 94547 | |
| Owner / Operator No. | 9929003 |
| Official Correspondent for the BioPlex 2200 MMRV IgG | |
| Official Correspondent Address | Bio-Rad Laboratories |
| 6565 185th Ave NE | |
| Redmond, WA 98052 | |
| Telephone | 425-881-8300 |
| Establishment Registration No. | 3022521 |
| Owner / Operator | Bio-Rad Laboratories |
| 6565 185th Ave NE | |
| Redmond, WA 98052 | |
| Official Correspondent | Mr. Christopher Bentsen |
| Telephone | (425) 498-1709 |
| Fax | (425) 498-1651 |
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CLASSIFICATION INFORMATION
| Classification Name | Multiplex immunoassay for measles virus, mumps virus,
rubella and varicella zoster virus |
|----------------------|---------------------------------------------------------------------------------------------|
| Common Name: | Multi-Analyte Detection System - MMRV IgG |
| Product Trade Name | BioPlex 2200 MMRV IgG on the BioPlex 2200 Multi-Analyte
Detection System |
| Device Class | Class II |
| Classification Panel | Microbiology |
| Regulation Number | 866.3520 |
| Product Code | OPL |
LEGALLY MARKETED EQUIVALENT (SE) DEVICES
| Comparative FDA Cleared | 510(k) Number | Decision |
|---|---|---|
| PREDICATE DEVICE | Date | |
| BioMerieux VIDAS Measles IgG (MSG) | 510(k) Exempt | N/A |
| BioMerieux VIDAS Mumps IgG (MPG) | 510(k) Exempt | N/A |
| Bio-Rad Rubella IgG EIA | K961053 | 9/14/1996 |
| BioMerieux VIDAS Varicella-Zoster IgG (VZV) | K923122 | 10/26/1992 |
DEVICE DESCRIPTION
The BioPlex 2200 MMRV IgG kit uses multiplex flow immunoassay, a methodology that greatly resembles traditional EIA, but permits simultaneous detection and identification of many antibodies in a single tube. Four (4) different populations of dyed beads are coated with antigens to identify the presence of IgG class antibodies associated with Measles, Mumps, Rubella and Varicella-zoster. The BioPlex 2200 System combines an aliquot of patient sample, sample diluent, and bead set reagent into a reaction vessel. The mixture is incubated at 37°C. After a wash cycle, anti-human IgG 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 three (3) distinct calibrator vials, supplied separately by Bio-Rad Laboratories.
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KIT COMPONENTS
BioPlex 2200 MMRV IgG Reagent Pack ( 665-2450). The reagent pack contains supplies sufficient for 100 tests.
| Vial | Description |
|---|---|
| Bead Set | One (1) 10 mL vial, containing dyed beads coated with Measles (Rubeola), |
| Mumps, Rubella, and VZV antigens plus an Internal Standard bead (ISB), a | |
| Serum Verification bead (SVB), and a Reagent Blank bead (RBB) in buffer | |
| with Glycerol and protein stabilizers (bovine). ProClin™ 300 (0.3%), sodium | |
| benzoate (0.1%) and sodium azide ( |