Search Results

The DYNEX SmartPLEX MMRV IgG Assay Kit is a multiplex immunoassay intended for the qualitative detection of IgG antibodies to Measles, Mumps, Rubella, and Varicella-Zoster Virus (VZV) in human serum. The DYNEX SmartPLEX MMRV IgG Assay Kit is intended for use with the DYNEX Multiplier Analyzer.

The DYNEX SmartPLEX MMRV IgG Assay Kit is intended to be used as an aid in the determination of serological status to Measles, Mumps, Rubella, and Varicella-Zoster Virus (VZV) in human serum from adults and pediatrics age above 1 year. This kit is not intended for screening blood or plasma donors.

The performance of this device has not been established for use in neonates, pediative patients below 1 year of age, and immunocompromised patients, or for use at point of care facilities.

The DYNEX SmartPLEX MMRV IgG Assay Kit (SmartPLEX MMRV IgG Assay) uses multiplex immunoassay, a methodology that greatly resembles traditional ELISA, while permits simultaneous detection and identification of different antibodies in a single well. The reaction is processed in a 96 well microtiter plate, with six polystyrene beads embedded in each well of the plate. Four (4) different beads are coated with antigens for the detection of IgG antibodies to Measles, Mumps, Rubella and Varicella-Zoster virus in human serum. Two additional beads are included in each reaction well as filler beads. Specimen processing is fully automated on the Multiplier Analyzer.

The Multiplier Analyzer adds the patient serum specimen and reagents to each well of the 96well plate, after which the mixture is incubated at 37°C with shaking. After a wash cycle, unbound antibodies from the patient's specimen are removed. Anti-human polyclonal IgG antibody conjugated to horseradish peroxidase (HRP) is added after which the mixture is incubated at 37°C with shaking. A second wash step removes excess conjuqate, then luminol substrate is added to each well. The amount of antibody captured by the antigen is determined by the chemiluminescence triggered by the attached HRP. Raw data is captured as light photons which are converted into relative light intensity units (RLU).

The Multiplier software analyzes the image and generates a report that details the mean RLU signal for each target bead (MMRV) by test sample. In every assay a calibrator is run. The DYNEX SmartPLEX MMRV IgG Assay Kit is qualitative and produces a result defined as negative (NEG), equivocal (EQV) or positive (POS) for each target analyte. The result is calculated in the Multiplier software by dividing the test sample RLU values by the mean calibrator RLU value to produce an index value for each target.

Here's an analysis of the acceptance criteria and study data for the DYNEX SmartPLEX MMRV IgG Assay Kit, as requested, based on the provided FDA 510(k) summary.

Device Name: DYNEX SmartPLEX MMRV IgG Assay Kit

Indications for Use: Qualitative detection of IgG antibodies to Measles, Mumps, Rubella, and Varicella-Zoster Virus (VZV) in human serum, as an aid in the determination of serological status. Intended for use with the DYNEX Multiplier Analyzer, in adults and pediatrics age above 1 year. Not intended for screening blood or plasma donors, neonates, pediatric patients below 1 year, or immunocompromised patients, or for point-of-care facilities.

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria values (e.g., "PPA must be >X%"). Instead, it presents the performance results obtained from the study and implies that these results were deemed acceptable for clearance. For this table, I will use the reported Clinical Performance (Method Comparison) as the primary indicator of device performance, specifically the Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) values.

Note: The acceptance criteria are "implied" as the document presents the results to demonstrate performance rather than explicitly stating pre-defined thresholds the device needed to meet for clearance.

2. Sample Sizes and Data Provenance

• Test Set Sample Size:
  • Clinical Performance (Method Comparison): N = 2512 retrospective human serum specimens.
    • Adults: N = 1676
    • Pregnant Women: N = 500
    • Pediatrics (age above 1 year): N = 336
  • Reproducibility and Within-Laboratory Precision: 22 serum samples, each tested 240 replicates.
  • Potential Cross-Reactivity: Variable N for each substance (e.g., ANA n=5, CMV n=6-8, EBV n=6-11).
• Data Provenance: Retrospective human serum specimens obtained from commercial vendors. The method comparison testing was performed at two US laboratory testing sites.

3. Number of Experts and Qualifications for Ground Truth

• The ground truth for clinical performance (method comparison) was established by FDA-cleared comparator tests, not through expert human readers or adjudicators for each individual case result. The agreement was measured against the results of these established assays.
• For specimens with equivocal results on the test device and comparator device, they were retested with two additional FDA-cleared methods.

4. Adjudication Method for the Test Set

• For equivocal results that remained equivocal after initial retesting with the comparator device, a "2/3 rule" was used to establish a consensus final comparator result. This means that if at least two out of the three comparator devices provided the same categorical result (Positive, Equivocal, or Negative), that result was taken as the consensus.
• Any remaining equivocal results (where no 2/3 consensus was reached or the consensus was still equivocal) were "counted against the clinical performance" of the SmartPLEX MMRV IgG Assay (this is implied by the 3x3 analysis where equivocal results from the test device are presented in comparison to the "Final Comparator Result").

5. MRMC Comparative Effectiveness Study

• No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This document describes the performance of an in vitro diagnostic (IVD) assay kit, which directly measures antibodies in serum. These types of devices do not typically involve human readers interpreting images or data to the extent that an MRMC study would be applicable. The performance is assessed by comparison to established laboratory methods or ground truth.

6. Standalone Performance

• Yes, standalone performance was done. The entire study is a standalone performance evaluation of the DYNEX SmartPLEX MMRV IgG Assay Kit in relation to comparator methods. The device's output (qualitative detection of IgG antibodies) is directly compared to the output of other FDA-cleared IVD assays. There is no "human-in-the-loop" component for this type of diagnostic assay, as its output is a direct measurement.

7. Type of Ground Truth Used

• The ground truth for the clinical performance study was primarily based on the results from one or more FDA-cleared comparator immunoassay devices. For ambiguous cases (equivocal results), a consensus derived from multiple FDA-cleared comparator methods using a "2/3 rule" was employed. This is a common method for establishing reference values in IVD studies where a perfect "gold standard" may not exist for all samples, or where the goal is to show substantial equivalence to established methods.

8. Sample Size for the Training Set

• The document does not specify a separate "training set" sample size or details about a training phase. For IVD assay kits, the development and optimization process (analogous to training) typically involves internal experimentation, formulation adjustments, and preliminary testing, rather than a distinct "training set" of patient samples in the same way an AI/ML algorithm would use labeled data. The provided data represents the validation/test set used for regulatory submission.

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

• Since a distinct "training set" as understood in AI/ML was not explicitly used or described in the context of this IVD assay kit, the concept of establishing ground truth for a training set is not directly applicable here. The focus is on the performance of the final, developed kit. The development process would have involved establishing specifications and ensuring the assay's ability to accurately detect the target antibodies, perhaps using characterized positive/negative panels, but this is not typically detailed as "ground truth for training" in 510(k) summaries for such devices.

Ask a specific question about this device

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 neonatal, pediatrics and immunocompromised patients, or for use at point of care facilities.

The BioPlex 2200 MMRV IgG kit uses multiplex flow immunoassay for simultaneous detection and identification of many antibodies in a single tube. Four (4) different populations of magnetic dyed beads are coated with antigens to identify the presence of IgG class antibodies against Measles. Mumps. Rubella and Varicella-zoster. The BioPlex 2200 System combines an aliquot of patient sample diluent, and bead set reagent into a reaction vessel. The mixture is incubated at 37℃. 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 re-suspended in wash buffer. The bead mixture then passes through the detector.

The identity of the dyed beads is determined by the fluorescence of the dyes, and the amount of antibody captured by the antigen is determined by the fluorescence of the attached PE. Raw data is calculated in relative fluorescence intensity (RFI). Three additional control 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.

The BioPlex 2200 MMRV IgG system is designed to detect IgG antibodies for Measles, Mumps, Rubella, and Varicella-zoster virus (VZV) in human serum and plasma. The acceptance criteria and supporting studies for this device, specifically focusing on the modification of QC testing frequency, are outlined below.

1. Table of Acceptance Criteria and Reported Device Performance

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

The provided document does not contain details regarding a specific test set, its sample size, or data provenance. The submission is a Special 510(k) for a modification (QC testing frequency) to an already cleared device, not for the initial clearance of the device itself. The evidence presented focuses on a risk analysis rather than a clinical performance study with patient samples to demonstrate equivalence for the modified aspect.

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

Not applicable. The document does not describe a clinical study with a test set requiring expert-established ground truth for performance evaluation of the modified QC procedure. The assessment was based on risk analysis and design control activities.

4. Adjudication Method for the Test Set

Not applicable, as no described test set requiring adjudication of results from clinical samples is present in the document.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

Not applicable. The BioPlex 2200 MMRV IgG is an in vitro diagnostic (IVD) assay designed for automated detection of antibodies, not an AI-assisted diagnostic tool that involves human reader interpretation.

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

The BioPlex 2200 MMRV IgG operates as a standalone automated system for detecting antibodies. The original device's performance, which this modification refers to, would have been established as standalone as per the nature of the device. The current submission focuses on a procedural change (QC frequency) rather than re-evaluating the core standalone performance.

7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)

For the original BioPlex 2200 MMRV IgG system, ground truth for establishing performance (sensitivity, specificity) would typically be based on:

• Reference laboratory methods: Comparison with established, validated serological tests (e.g., IFA, EIA) from reference laboratories.
• Clinical status: Correlation with patient vaccination history, known infection status, or immune response.
• Known positive/negative panels: Use of well-characterized serum panels with known antibody status.

However, the provided Special 510(k) document for the modification does not detail the ground truth used for the initial device or for evaluating the impact of the QC frequency change. The current submission relies on a risk assessment rather than a clinical performance study against a ground truth.

8. The Sample Size for the Training Set

Not applicable. This is an in vitro diagnostic device, not an AI/ML model that typically undergoes specific "training" with a dataset in the same way. The development of such assays involves optimization and calibration using characterized samples, but not a "training set" in the context of machine learning.

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

Not applicable, for the reasons stated in point 8.

Ask a specific question about this device

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.

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.

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. It is intended for use with the Bio-Rad BioPlex 2200 System as an aid in determining serological status to these viruses. It is not intended for screening blood/plasma donors, and performance has not been established for neonates, pediatrics, immunocompromised patients, or point-of-care facilities.

Here's an analysis of the acceptance criteria and the studies performed:

1. Table of Acceptance Criteria and Reported Device Performance

The submission does not explicitly state pre-defined acceptance criteria (e.g., minimum sensitivity/specificity percentages). Instead, the performance is demonstrated through comparative testing against legally marketed predicate devices and reproducibility studies. The tables below summarize the reported device performance.

Comparative Testing: BioPlex 2200 MMRV IgG vs. Commercially Available EIAs

Retrospective Negative Samples: BioPlex 2200 MMRV IgG vs. EIA

Reproducibility (Total %CV for Serum, across sites, days, runs)

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

• Prospective Comparative Testing:
  • Pregnant Women: N = 396 serum samples. Data provenance: Not explicitly stated, but the study was conducted at 3 U.S. clinical trial sites. Retrospective or prospective nature is not specified for collection.
  • Measles, Mumps, Rubella, or VZV Test Ordered: N = 1183 serum samples. This population included (N = 790) samples submitted for routine testing and (N = 393) samples for pre-employment evaluation. Data provenance: Not explicitly stated, but the study was conducted at 3 U.S. clinical trial sites.
• Retrospective Comparative Testing (Negative Samples):
  • Measles IgG: N = 93 serum samples.
  • Mumps IgG: N = 96 serum samples.
  • Rubella IgG: N = 268 serum samples.
  • VZV IgG: N = 143 serum samples.
  • Data provenance: Not explicitly stated, but implies these were pre-existing samples.
• CDC Rubella Evaluation Serum Panel: N = 100 serum samples (82 positive, 18 negative). Data provenance: Provided by the CDC.
• Reproducibility Studies: A "reproducibility panel" was prepared, consisting of positive panel members in serum, EDTA plasma, and sodium heparin plasma, along with a positive and negative control. The exact number of panel members is not explicitly stated beyond "varying levels of antibodies" and a "positive control." Each panel member and controls were tested in quadruplicate on 1 run per day over 5 days at each of 3 sites (4 replicates x 1 run x 5 days x number of panel members = total Sample N for reproducibility analysis, which for each measured point was N=60).

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

The ground truth for the comparative testing was established using commercially available EIA (Enzyme Immunoassay) predicate devices, which are conventional laboratory tests. No human experts establishing a ground truth in the manner of, for example, radiologists interpreting images, are mentioned for these studies.

For the CDC Rubella Evaluation Serum Panel, the samples were "masked, characterized" by the CDC. This implies expert characterization by the CDC, but the specific number and qualifications of experts are not described.

4. Adjudication Method for the Test Set

• Prospective Comparative Testing:
  • For Mumps and Measles, equivocal results on the commercially available EIAs were "further tested on two additional commercially available EIAs for consensus." This implies a 2 out of 3 consensus method for adjudicating equivocal results from the primary predicate EIA, using the two additional EIAs. The exact consensus rule (e.g., majority or all agree) is not explicitly stated but "consensus" suggests agreement among at least two.
  • For Rubella, equivocal results on the commercially available EIA were "re-tested on the commercially available EIA, following the manufacturer's recommendations." This is a re-testing procedure, not a multi-reader adjudication.
  • For VZV, no specific adjudication method for equivocal results is mentioned in the tables provided.
• Retrospective Comparative Testing:
  • For Measles and Mumps negative samples, they were "selected using a consensus of two out of three commercially available EIAs." This is a pre-selection method for the test samples based on consensus, rather than adjudication of results from the BioPlex device.
  • For Rubella and VZV negative samples, they were "selected using the respective commercially available EIAs used for the comparative analysis." No consensus method is mentioned here for selection.

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

No MRMC comparative effectiveness study was described. The study focuses on comparing the BioPlex device's performance to existing immunoassays, rather than assessing human reader performance with and without AI assistance.

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

Yes, the studies described are standalone performance evaluations of the BioPlex 2200 MMRV IgG kit against predicate devices. The device is an automated immunoassay system, and its performance metrics (agreement, reproducibility) reflect its standalone operational capabilities. There is no human-in-the-loop component mentioned in its operational or evaluation methodology that would constitute an "AI assistance" scenario.

7. The Type of Ground Truth Used

The primary ground truth for evaluating the BioPlex 2200 MMRV IgG kit's performance was established using results from legally marketed, commercially available EIA (Enzyme Immunoassay) predicate devices.

• For Measles and Mumps, this involved consensus results from two out of three commercially available EIAs for equivocal samples.
• For Rubella, re-testing with the predicate EIA was used for equivocal results.
• For the CDC Rubella panel, the ground truth was "masked, characterized" CDC reference sera.

8. The Sample Size for the Training Set

No training set is explicitly mentioned, as this is a traditional immunoassay device, not a machine learning or AI-driven algorithm in the context of typical training/validation/test sets for pattern recognition. The device is calibrated using a "set of three (3) distinct calibrator vials, supplied separately by Bio-Rad Laboratories" and controls are used for quality assurance.

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

Since no traditional "training set" in the context of AI/ML was used, this question is not applicable. The device's operational parameters are based on established immunoassay principles, calibration, and quality control using defined calibrator and control materials.

Ask a specific question about this device