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The BioPlex 2200 ToRC IgM kit is a multiplex flow immunoassay intended for the qualitative detection of IgM antibodies to Toxoplasma gondii), Rubella, and Cytomegalovirus (CMV) in human serum and plasma (K3 EDTA, lithium heparin, or sodium heparin).
The BioPlex 2200 ToRC IgM kit is intended for use with the Bio-Rad BioPlex 2200 System.
This kit is intended as an aid in the diagnosis of a current or recent T. gondii, Rubella and/or CMV infection, in individuals suspected of having one of the respective disease states, including women of child bearing age.
This assay is not FDA cleared or approved for use in testing (screening) blood or plasma donors.
Performance characteristics for the ToRC IgM assay have not been evaluated in immunosuppressed or organ transplant individuals. Performance characteristics of this kit have not been established for use in neonatal screening or for use at point of care facilities.
The BioPlex 2200 ToRC IgM Calibrator Set is intended for the BioPlex 2200 ToRC IgM Reagent Pack.
The BioPlex 2200 ToRC IgM Control Set is intended for use as an assayed quality control to monitor the overall performance of the BioPlex 2200 Instrument and BioPlex 2200 ToRC IgM Reagent Pack in the clinical laboratory.
BioPlex ToRC IgM Reagent Pack includes the following components:
- One (1) 10 mL vial, containing dyed beads coated with lysates of T. gondii, Rubella and CMV ● plus an Internal Standard bead (ISB) and a Serum Verification bead (SVB) in buffer with Glycerol and protein stabilizers (bovine and caprine). ProClin 300 (≤ 0.3%), sodium benzoate (≤ 0.1%) and sodium azide (< 0.1%) as preservatives.
- . One (1) 5 mL vial, containing phycoerythrin-conjugated murine monoclonal anti-human IgM antibody and phycoerythrin-conjugated murine monoclonal anti-human FXIII antibody, in buffer with protein stabilizers (bovine and murine). ProClin 300 (≤ 0.3%), sodium benzoate (≤ 0.1%) and sodium azide (< 0.1%) as preservatives.
- One (1) 10 mL vial, containing goat anti-human IgG antibody and protein stabilizers (bovine . and murine) in buffer. ProClin 300 (< 0.3%), sodium benzoate (< 0.1%) and sodium azide (< 0.1%) as preservatives.
BioPlex 2200 ToRC IgM Calibrator set contains two (2) 0.5 mL vials. The calibrators are provided in a human serum matrix made from defibrinated plasma with added known analyte concentrations consisting of HuCAL® recombinant IgM antibodies for rubella and human disease state plasma derived antibodies for T. gondii and CMV. All calibrators contain ProClin 300 (≤ 0.3%), sodium benzoate (≤ 0.1%) and sodium azide (< 0.1%) as preservatives.
BioPlex 2200 ToRC IgM Control set contains two (2) 1.5 mL Positive Control serum vials, containing human disease state plasma derived IgM antibodies to T. gondii and CMV, and HuCAL® recombinant IgM antibodies to Rubella in a human serum matrix made from defibrinated plasma; and two (2) 1.5 mL Negative Control serum vials, in a human serum matrix made from defibrinted plasma. All controls contain Amikacin (0.003%), Cycloheximide (C15H23NO4) (0.009%), Amphotericin B (0.002%), Cefotaxime Sodium (0.002%), Ciprofloxacin (0.005%), ProClin 300 (≤ 0.3%), sodium benzoate (≤ 0.1%) and sodium azide (< 0.1%).
Additional materials required but not supplied include BioPlex 2200 Sheath Fluid containing Phosphate Buffered Saline (PBS), ProClin 300 (0.03%) and sodium azide (<0.1%) as preservatives; and BioPlex 2200 Wash Solution containing Phosphate Buffered Saline (PBS) and Tween 20, ProClin 300 (0.03%) and sodium azide (<0.1%) as preservatives.
Here's an analysis of the provided text to extract information about the acceptance criteria and the study proving the device's performance, as requested.
The provided text describes the performance characteristics of the BioPlex 2200 ToRC IgM kit, which is a multiplex flow immunoassay for detecting IgM antibodies to Toxoplasma gondii, Rubella, and Cytomegalovirus (CMV).
Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated as a section titled "Acceptance Criteria" with pass/fail metrics. Instead, the document presents various analytical and clinical performance studies, and the results of these studies implicitly represent the device's acceptable performance. For the purpose of this response, I will infer the acceptance criteria from the reported performance, particularly where quantitative results are presented.
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Metric Category | Specific Metric (Inferred Acceptance Criteria) | Reported Device Performance | Comments |
|---|---|---|---|
| Analytical Performance | Precision/Reproducibility | ||
| Within-run Precision | See tables below | Measured as SD for AI < 0.8 and %CV for AI > 0.8. Generally low %CVs (e.g., 3.7% to 14.2% for Negative samples, 3.8% to 7.2% for Positives). | |
| Between-run Precision | See tables below | Generally low %CVs across analytes and sample types. | |
| Between-day Precision | See tables below | Generally low %CVs across analytes and sample types. | |
| Total Reproducibility (Across Sites) | See tables below | Generally low %CVs (e.g., Toxo IgM Total %CV for high positive is 10.7%). | |
| Analytical Specificity | Cross-Reactivity (Percent Negative Agreement) | Assessed by testing against various potential cross-reactants. Primarily 100% negative agreement, with few exceptions (e.g., Rubella IgM with Hypergamma-globulinemia IgM: 20/21 negative; Rubella IgM with Parvovirus B19 IgM: 13/14 negative; VZV IgM with T. gondii IgM and CMV IgM: 12/13 negative for both). | |
| Interfering Substances | No significant interference observed. | Tested substances include Hemoglobin, Bilirubin, Cholesterol, Red Blood Cells, Gamma Globulin, Triglycerides, Beta Carotene, Protein, Ascorbic Acid, Sodium Heparin, Lithium Heparin, EDTA. | |
| Clinical Performance | Method Comparison (Prospective Samples) | Comparison against commercially available predicate devices. | |
| T. gondii IgM (Pregnant Women) | Positive Agreement: N/A, Negative Agreement: 98.0% (196/200) CI 95.0-99.2% | High negative agreement. | |
| T. gondii IgM (Test Ordered) | Positive Agreement: N/A, Negative Agreement: 97.4% (481/494) CI 95.6-98.5% | High negative agreement. | |
| Rubella IgM (Pregnant Women) | Positive Agreement: N/A, Negative Agreement: 100.0% (198/198) CI 98.1-100.0% | Excellent negative agreement. | |
| Rubella IgM (Test Ordered) | Positive Agreement: 40.0% (4/10) CI 16.8-68.7%, Negative Agreement: 99.6% (498/500) CI 98.6-99.9% | Lower positive agreement for test-ordered samples, but very high negative agreement. Note: 10 samples considered positive by predicate, 5 negative and 1 equivocal by BioPlex. | |
| CMV IgM (Pregnant Women) | Positive Agreement: 50.0% (8/16) CI 28.0-72.0%, Negative Agreement: 100.0% (183/183) CI 97.9-100.0% | Lower positive agreement for pregnant women, but excellent negative agreement. Discrepant samples were confirmed negative by another FDA-cleared device. | |
| CMV IgM (Test Ordered) | Positive Agreement: 55.6% (20/36) CI 39.6-70.5%, Negative Agreement: 98.6% (480/487) CI 97.1-99.3% | Lower positive agreement for test-ordered samples, but high negative agreement. Discrepant samples were confirmed negative by another FDA-cleared device. | |
| Method Comparison (Retrospective Samples - Presumptive Positive) | Comparison against commercially available predicate devices. | ||
| T. gondii IgM | Positive Agreement: 97.1% (203/209) CI 93.9-98.7% | High positive agreement. | |
| Rubella IgM | Positive Agreement: 98.0% (96/98) CI 92.9-99.4% | High positive agreement. | |
| CMV IgM | Positive Agreement: 98.5% (198/201) CI 95.7-99.5% | High positive agreement. | |
| Clinical Supportive Data | Correlation with CDC Evaluation Panels (T. gondii IgM) | Positive Agreement: 100.0%, Negative Agreement: 100.0% | Excellent agreement with CDC reference sera. |
| Seroconversion Testing | Qualitative agreement with predicate devices for seroconversion panels. | Demonstrates expected seroconversion patterns. | |
| IgM Specificity (DTT Treatment) | High reduction in IgM activity (very low % recovery - typically <3%). | Confirms specificity for IgM antibodies. |
Precision Data Tables (as presented in the document):
BioPlex 2200 Toxo IgM – CLSI EP5-A3 Precision
| Sample Type | T. gondii IgM Panel Members | N | Mean (AI) | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Within Run | Between Run | Between Day | Total | ||||||||
| Serum | Negative | 80 | 0.5 | 0.039 | 7.9% | 0.000 | 0.0% | 0.007 | 1.3% | 0.039 | 8.0% |
| High Negative | 80 | 0.7 | 0.034 | 4.8% | 0.011 | 1.6% | 0.012 | 1.7% | 0.037 | 5.3% | |
| Cut-Off | 80 | 0.9 | 0.050 | 5.5% | 0.000 | 0.0% | 0.031 | 3.4% | 0.059 | 6.5% | |
| Cut-Off | 80 | 1.0 | 0.064 | 6.3% | 0.000 | 0.0% | 0.030 | 2.9% | 0.071 | 6.9% | |
| Low Positive | 80 | 1.3 | 0.057 | 4.3% | 0.042 | 3.2% | 0.039 | 2.9% | 0.081 | 6.1% | |
| Positive | 80 | 2.3 | 0.113 | 5.0% | 0.000 | 0.0% | 0.034 | 1.5% | 0.118 | 5.2% | |
| Positive | 80 | 3.3 | 0.164 | 4.9% | 0.034 | 1.0% | 0.053 | 1.6% | 0.175 | 5.3% | |
| Potassium EDTA | Negative | 80 | 0.5 | 0.019 | 3.9% | 0.000 | 0.0% | 0.002 | 0.4% | 0.019 | 3.9% |
| High Negative | 80 | 0.7 | 0.046 | 6.2% | 0.000 | 0.0% | 0.027 | 3.7% | 0.053 | 7.2% | |
| Cut-Off | 80 | 0.9 | 0.056 | 6.3% | 0.000 | 0.0% | 0.017 | 1.9% | 0.059 | 6.6% | |
| Low Positive | 80 | 1.2 | 0.073 | 6.0% | 0.000 | 0.0% | 0.049 | 4.0% | 0.088 | 7.3% | |
| Positive | 80 | 2.0 | 0.089 | 4.4% | 0.037 | 1.8% | 0.062 | 3.1% | 0.114 | 5.7% | |
| Positive | 80 | 3.2 | 0.167 | 5.3% | 0.059 | 1.9% | 0.098 | 3.1% | 0.203 | 6.4% | |
| Sodium Heparin | Negative | 80 | 0.4 | 0.045 | 10.3% | 0.000 | 0.0% | 0.018 | 4.1% | 0.048 | 11.1% |
| High Negative | 80 | 0.7 | 0.032 | 4.3% | 0.030 | 4.0% | 0.025 | 3.4% | 0.050 | 6.8% | |
| Cut-Off | 80 | 0.9 | 0.058 | 6.2% | 0.025 | 2.7% | 0.022 | 2.4% | 0.067 | 7.2% | |
| Low Positive | 80 | 1.3 | 0.068 | 5.3% | 0.000 | 0.0% | 0.035 | 2.7% | 0.076 | 5.9% | |
| Positive | 80 | 2.1 | 0.109 | 5.3% | 0.000 | 0.0% | 0.060 | 2.9% | 0.124 | 6.0% | |
| Positive | 80 | 3.1 | 0.117 | 3.8% | 0.000 | 0.0% | 0.049 | 1.6% | 0.127 | 4.1% | |
| Lithium Heparin | Negative | 80 | 0.5 | 0.050 | 10.9% | 0.011 | 2.4% | 0.010 | 2.3% | 0.052 | 11.4% |
| High Negative | 80 | 0.7 | 0.042 | 6.0% | 0.000 | 0.0% | 0.017 | 2.4% | 0.045 | 6.4% | |
| Cut-Off | 80 | 0.9 | 0.061 | 6.7% | 0.000 | 0.0% | 0.018 | 2.0% | 0.064 | 7.0% | |
| Low Positive | 80 | 1.3 | 0.063 | 5.0% | 0.050 | 4.0% | 0.019 | 1.5% | 0.083 | 6.6% | |
| Positive | 80 | 2.0 | 0.108 | 5.4% | 0.045 | 2.2% | 0.031 | 1.6% | 0.121 | 6.1% | |
| Positive | 80 | 3.1 | 0.145 | 4.7% | 0.000 | 0.0% | 0.064 | 2.1% | 0.159 | 5.1% |
BioPlex 2200 Rubella IgM – CLSI EP5-A3 Precision
| Sample Type | Rubella IgM Panel Members | N | Mean (AI) | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Within Run | Between Run | Between-Day | Total | ||||||||
| Serum | Negative | 80 | 0.3 | 0.011 | 3.7% | 0.000 | 0.0% | 0.000 | 0.0% | 0.011 | 3.7% |
| High Negative | 80 | 0.6 | 0.040 | 6.6% | 0.000 | 0.0% | 0.016 | 2.6% | 0.043 | 7.1% | |
| Cut-Off | 80 | 0.8 | 0.049 | 5.9% | 0.000 | 0.0% | 0.014 | 1.6% | 0.051 | 6.1% | |
| Cut-Off | 80 | 1.1 | 0.066 | 5.8% | 0.000 | 0.0% | 0.031 | 2.7% | 0.073 | 6.4% | |
| Low Positive | 80 | 1.2 | 0.063 | 5.4% | 0.027 | 2.3% | 0.027 | 2.2% | 0.074 | 6.3% | |
| Positive | 80 | 1.5 | 0.085 | 5.7% | 0.039 | 2.6% | 0.000 | 0.0% | 0.094 | 6.2% | |
| Positive | 80 | 2.7 | 0.146 | 5.5% | 0.000 | 0.0% | 0.000 | 0.0% | 0.146 | 5.5% | |
| Positive | 80 | 3.0 | 0.157 | 5.3% | 0.035 | 1.2% | 0.091 | 3.0% | 0.185 | 6.2% | |
| Potassium EDTA | Negative | 80 | 0.3 | 0.011 | 3.7% | 0.000 | 0.0% | 0.000 | 0.0% | 0.011 | 3.7% |
| High Negative | 80 | 0.6 | 0.045 | 7.0% | 0.000 | 0.0% | 0.029 | 4.6% | 0.053 | 8.4% | |
| Cut-Off | 80 | 1.0 | 0.055 | 5.6% | 0.016 | 1.6% | 0.026 | 2.7% | 0.063 | 6.5% | |
| Low Positive | 80 | 1.1 | 0.064 | 5.7% | 0.016 | 1.4% | 0.016 | 1.4% | 0.068 | 6.1% | |
| Positive | 80 | 1.6 | 0.084 | 5.4% | 0.000 | 0.0% | 0.057 | 3.7% | 0.101 | 6.5% | |
| Positive | 80 | 2.4 | 0.118 | 4.9% | 0.000 | 0.0% | 0.084 | 3.5% | 0.145 | 6.0% | |
| Positive | 80 | 3.0 | 0.168 | 5.6% | 0.000 | 0.0% | 0.103 | 3.4% | 0.198 | 6.5% | |
| Sodium Heparin | Negative | 80 | 0.3 | 0.045 | 13.3% | 0.011 | 3.3% | 0.014 | 4.1% | 0.048 | 14.4% |
| High Negative | 80 | 0.6 | 0.042 | 6.8% | 0.011 | 1.8% | 0.023 | 3.7% | 0.049 | 8.0% | |
| Cut-Off | 80 | 1.0 | 0.045 | 4.6% | 0.034 | 3.4% | 0.029 | 2.9% | 0.063 | 6.4% | |
| Low Positive | 80 | 1.1 | 0.066 | 5.8% | 0.016 | 1.4% | 0.018 | 1.6% | 0.070 | 6.2% | |
| Positive | 80 | 1.6 | 0.092 | 5.7% | 0.000 | 0.0% | 0.044 | 2.7% | 0.102 | 6.3% | |
| Positive | 80 | 2.5 | 0.123 | 4.9% | 0.039 | 1.5% | 0.036 | 1.4% | 0.134 | 5.3% | |
| Positive | 80 | 3.2 | 0.155 | 4.9% | 0.019 | 0.6% | 0.029 | 0.9% | 0.159 | 5.0% | |
| Lithium Heparin | Negative | 80 | 0.3 | 0.019 | 6.5% | 0.000 | 0.0% | 0.000 | 0.0% | 0.019 | 6.5% |
| High Negative | 80 | 0.6 | 0.047 | 8.3% | 0.000 | 0.0% | 0.023 | 4.1% | 0.053 | 9.2% | |
| Cut-Off | 80 | 1.0 | 0.063 | 6.6% | 0.000 | 0.0% | 0.032 | 3.3% | 0.071 | 7.4% | |
| Low Positive | 80 | 1.2 | 0.079 | 6.6% | 0.000 | 0.0% | 0.027 | 2.2% | 0.083 | 7.0% | |
| Positive | 80 | 1.5 | 0.089 | 5.9% | 0.047 | 3.1% | 0.026 | 1.7% | 0.105 | 6.8% | |
| Positive | 80 | 2.6 | 0.158 | 6.1% | 0.000 | 0.0% | 0.000 | 0.0% | 0.158 | 6.1% | |
| Positive | 80 | 3.1 | 0.150 | 4.8% | 0.070 | 2.2% | 0.039 | 1.3% | 0.170 | 5.5% |
BioPlex 2200 CMV IgM – CLSI EP5-A3 Precision
| Sample Type | CMV IgM Panel Members | N | Mean (AI) | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Within Run | Between Run | Between-Day | Total | ||||||||
| Serum | Negative | 80 | 0.4 | 0.039 | 10.3% | 0.019 | 5.2% | 0.005 | 1.5% | 0.044 | 11.6% |
| High Negative | 80 | 0.8 | 0.060 | 7.5% | 0.000 | 0.0% | 0.017 | 2.2% | 0.063 | 7.8% | |
| Cut-Off | 80 | 1.1 | 0.065 | 6.1% | 0.030 | 2.8% | 0.032 | 3.0% | 0.078 | 7.4% | |
| Cut-Off | 80 | 1.2 | 0.152 | 12.2% | 0.000 | 0.0% | 0.000 | 0.0% | 0.152 | 12.2% | |
| Low Positive | 80 | 1.2 | 0.089 | 7.2% | 0.000 | 0.0% | 0.000 | 0.0% | 0.089 | 7.2% | |
| Positive | 80 | 1.7 | 0.122 | 7.0% | 0.000 | 0.0% | 0.000 | 0.0% | 0.122 | 7.0% | |
| Positive | 80 | 3.0 | 0.196 | 6.6% | 0.000 | 0.0% | 0.030 | 1.0% | 0.198 | 6.7% | |
| Positive | 80 | 3.1 | 0.214 | 7.0% | 0.000 | 0.0% | 0.077 | 2.5% | 0.227 | 7.4% | |
| Potassium EDTA | Negative | 80 | 0.3 | 0.047 | 13.8% | 0.000 | 0.0% | 0.022 | 6.5% | 0.052 | 15.3% |
| High Negative | 80 | 0.8 | 0.047 | 6.2% | 0.030 | 3.9% | 0.015 | 1.9% | 0.058 | 7.5% | |
| Cut-Off | 80 | 1.1 | 0.070 | 6.5% | 0.000 | 0.0% | 0.028 | 2.6% | 0.075 | 7.0% | |
| Low Positive | 80 | 1.3 | 0.089 | 6.7% | 0.000 | 0.0% | 0.000 | 0.0% | 0.089 | 6.7% | |
| Positive | 80 | 1.9 | 0.128 | 6.8% | 0.000 | 0.0% | 0.078 | 4.1% | 0.150 | 8.0% | |
| Positive | 80 | 3.1 | 0.185 | 6.0% | 0.000 | 0.0% | 0.088 | 2.9% | 0.205 | 6.7% | |
| Positive | 80 | 2.9 | 0.196 | 6.7% | 0.000 | 0.0% | 0.122 | 4.2% | 0.231 | 7.9% | |
| Sodium Heparin | Negative | 80 | 0.3 | 0.022 | 7.5% | 0.000 | 0.0% | 0.000 | 0.0% | 0.022 | 7.5% |
| High Negative | 80 | 0.8 | 0.065 | 7.8% | 0.000 | 0.0% | 0.000 | 0.0% | 0.065 | 7.8% | |
| Cut-Off | 80 | 0.8 | 0.047 | 6.3% | 0.022 | 3.0% | 0.017 | 2.3% | 0.055 | 7.3% | |
| Low Positive | 80 | 1.3 | 0.083 | 6.2% | 0.019 | 1.4% | 0.000 | 0.0% | 0.085 | 6.3% | |
| Positive | 80 | 2.0 | 0.121 | 6.0% | 0.000 | 0.0% | 0.048 | 2.4% | 0.130 | 6.5% | |
| Positive | 80 | 3.1 | 0.193 | 6.2% | 0.000 | 0.0% | 0.064 | 2.1% | 0.203 | 6.5% | |
| Positive | 80 | 3.1 | 0.167 | 5.4% | 0.000 | 0.0% | 0.076 | 2.5% | 0.184 | 6.0% | |
| Lithium Heparin | Negative | 80 | 0.3 | 0.040 | 14.2% | 0.000 | 0.0% | 0.000 | 0.0% | 0.040 | 14.2% |
| High Negative | 80 | 0.7 | 0.060 | 8.8% | 0.000 | 0.0% | 0.022 | 3.3% | 0.064 | 9.4% | |
| Cut-Off | 80 | 1.0 | 0.085 | 8.7% | 0.000 | 0.0% | 0.037 | 3.7% | 0.093 | 9.5% | |
| Low Positive | 80 | 1.4 | 0.104 | 7.5% | 0.000 | 0.0% | 0.055 | 4.0% | 0.118 | 8.5% | |
| Positive | 80 | 1.9 | 0.133 | 7.1% | 0.019 | 1.0% | 0.042 | 2.2% | 0.140 | 7.6% | |
| Positive | 80 | 3.0 | 0.222 | 7.5% | 0.096 | 3.2% | 0.000 | 0.0% | 0.242 | 8.1% | |
| Positive | 80 | 2.7 | 0.153 | 5.7% | 0.030 | 1.1% | 0.000 | 0.0% | 0.156 | 5.8% |
Reproducibility Data Tables (across 3 sites):
BioPlex 2200 Toxo IgM - CLSI EP15-A3 Reproducibility
| Panel Member | Mean (AI) | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Within Run | Between Run | Between Day | Between Site | Total | |||||||
| Positive Control | 2.0 | 0.092 | 4.7% | 0.103 | 5.2% | 0.000 | 0.0% | 0.178 | 9.0% | 0.225 | 11.4% |
| Low Negative | 0.2 | 0.029 | 13.8% | 0.016 | 7.6% | 0.000 | 0.0% | 0.010 | 4.7% | 0.035 | 16.5% |
| High Negative | 0.8 | 0.040 | 4.8% | 0.012 | 1.5% | 0.028 | 3.3% | 0.100 | 12.0% | 0.112 | 13.4% |
| Low Positive | 1.3 | 0.051 | 4.0% | 0.032 | 2.5% | 0.023 | 1.8% | 0.148 | 11.6% | 0.162 | 12.7% |
| Mid Positive | 2.2 | 0.081 | 3.7% | 0.058 | 2.6% | 0.032 | 1.5% | 0.257 | 11.7% | 0.278 | 12.7% |
| High Positive | 3.2 | 0.172 | 5.3% | 0.093 | 2.9% | 0.043 | 1.3% | 0.280 | 8.7% | 0.344 | 10.7% |
BioPlex 2200 Rubella IgM - CLSI EP15-A3 Reproducibility
| Panel Member | Mean (AI) | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Within Run | Between Run | Between Day | Between Site | Total | |||||||
| Positive Control | 1.9 | 0.086 | 4.5% | 0.053 | 2.8% | 0.043 | 2.3% | 0.198 | 10.5% | 0.227 | 12.0% |
| Low Negative | 0.3 | 0.026 | 9.3% | 0.013 | 4.7% | 0.000 | 0.0% | 0.042 | 15.3% | 0.051 | 18.5% |
| High Negative | 0.8 | 0.048 | 6.2% | 0.000 | 0.0% | 0.026 | 3.3% | 0.097 | 12.4% | 0.111 | 14.2% |
| Low Positive | 1.2 | 0.056 | 4.8% | 0.019 | 1.7% | 0.000 | 0.0% | 0.143 | 12.3% | 0.155 | 13.3% |
| Mid Positive | 1.5 | 0.051 | 3.5% | 0.014 | 1.0% | 0.027 | 1.8% | 0.197 | 13.6% | 0.206 | 14.2% |
| High Positive | 2.8 | 0.139 | 4.9% | 0.015 | 0.5% | 0.030 | 1.1% | 0.328 | 11.6% | 0.358 | 12.6% |
BioPlex 2200 CMV IgM - CLSI EP15-A3 Reproducibility
| CMV IgM Panel Member | Mean (AI) | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Within Run | Between Run | Between Day | Between Site | Total | |||||||
| Positive Control | 2.3 | 0.098 | 4.3% | 0.053 | 2.4% | 0.058 | 2.6% | 0.145 | 6.4% | 0.192 | 8.5% |
| Low Negative | 0.3 | 0.032 | 9.1% | 0.000 | 0.0% | 0.013 | 3.8% | 0.052 | 15.1% | 0.063 | 18.1% |
| High Negative | 0.7 | 0.048 | 7.0% | 0.011 | 1.6% | 0.009 | 1.3% | 0.062 | 9.0% | 0.080 | 11.6% |
| Low Positive | 1.2 | 0.071 | 6.2% | 0.029 | 2.5% | 0.000 | 0.0% | 0.096 | 8.3% | 0.123 | 10.6% |
| Mid Positive | 1.7 | 0.081 | 4.7% | 0.021 | 1.3% | 0.038 | 2.3% | 0.208 | 12.2% | 0.227 | 13.4% |
| High Positive | 2.9 | 0.146 | 5.1% | 0.026 | 0.9% | 0.065 | 2.3% | 0.257 | 9.0% | 0.304 | 10.6% |
2. Sample Size Used for the Test Set and Data Provenance
- Precision/Reproducibility:
- CLSI EP5-A3 Precision: 80 data points per panel member for each analyte (T. gondii, Rubella, CMV) and each sample matrix (Serum, Potassium EDTA, Sodium Heparin, Lithium Heparin). This means 80 samples per specific condition.
- CLSI EP15-A3 Reproducibility: 120 replicates per panel member (4 replicates x 2 runs x 5 days x 3 sites). There were 6 panel members for each analyte. This equates to 720 samples per analyte across three sites for reproducibility.
- Cross-Reactivity: At least 10 specimens per potential cross-reactant for each of the three antibody assays.
- Matrix Comparison: A minimum of 40 sets of paired serum and plasma samples per analyte (N=51 to 60 for each analyte and matrix comparison).
- Method Comparison (Prospective):
- 2129 prospective samples in total.
- ~700 samples per analyte (T. gondii, Rubella, CMV).
- 200 pregnant women samples for each analyte.
- Data Provenance: Samples were submitted for T. gondii, Rubella, or CMV testing. These were prospective samples collected at 3 U.S. clinical testing sites.
- Method Comparison (Retrospective):
- 210 T. gondii IgM presumptive positive samples (134 female, 76 male).
- 101 Rubella IgM presumptive positive samples (44 female, 57 male).
- 213 CMV IgM presumptive positive samples (119 female, 94 male).
- Data Provenance: Presumed positive banked samples for ToRC IgM. Retrospective.
- Correlation with CDC Evaluation Panels: 97 samples for T. gondii IgM (CDC Panel). Data provenance from CDC.
- Seroconversion Testing: Commercially available seroconversion panels for T. gondii, Rubella, and CMV IgM.
- IgM Specificity: 10 samples for each analyte (T. gondii, Rubella, CMV).
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not explicitly mention "experts" in the context of establishing ground truth for the test set. Instead, for clinical performance, the ground truth for comparative studies was established by:
- Results from commercially available predicate T. gondii, Rubella, and CMV IgM assays.
- In cases of discrepancy, another FDA-cleared device was used for confirmation (e.g., for CMV IgM method comparison).
- For the CDC panel, the CDC's characterization of the samples served as the ground truth.
This implies that the "ground truth" relies on the established performance and regulatory clearance of existing in vitro diagnostic devices and reference panels, rather than expert human interpretation in the way it might for imaging studies. Healthcare professionals running these predicate assays are implied to be qualified clinical laboratory personnel, but no specific number or qualification of individual experts is provided as is typical for AI/imaging ground truth studies.
4. Adjudication Method for the Test Set
The document does not describe an adjudication method in the context of human readers reviewing results. For the comparative studies, discrepancies between the new device and the predicate device were investigated using another FDA-cleared device to confirm serological status. This serves as a form of adjudication by a third, independent, and validated method.
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
No. This is an in vitro diagnostic (IVD) device, not an AI for human-in-the-loop performance improvement study. The performance is assessed based on direct assay results (qualitative detection of antibodies), not on human reader performance. Therefore, an MRMC study or calculation of human reader improvement with AI assistance is not applicable and was not performed.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes. The entire performance evaluation for the BioPlex 2200 ToRC IgM kit is effectively a "standalone" assessment of the device's ability to qualitatively detect IgM antibodies. The device generates an Antibody Index (AI) result, which is then interpreted against a defined cut-off (e.g., >1.1 AI for positive, <0.9 AI for negative, 0.9-1.1 AI for equivocal). This is an algorithm-only performance in the context of an IVD, as it directly measures analytes in a sample.
7. The Type of Ground Truth Used
The primary ground truth used for method comparison studies was:
- Results from established, commercially available, and presumably FDA-cleared predicate IVD devices.
- For specific discrepant results, another FDA-cleared device was used, implying a reliance on a higher standard or independent confirmation through a validated method.
- For T. gondii IgM, CDC reference sera panels were used, representing a type of reference standard/outcome data (serological status defined by reference lab/panel).
- Seroconversion panels represent samples with known disease progression/antibody development over time, establishing dynamic ground truth.
- DTT treatment for IgM specificity provides experimental evidence that the signal is specifically from IgM antibodies, using a chemical method to selectively inactivate IgM.
8. The Sample Size for the Training Set
The document does not explicitly describe a "training set" in the context of machine learning or AI. This is a traditional IVD device, and its performance is established through calibration and validation studies, not by training a machine learning model on a dataset.
However, the "Assay cut-off" section mentions: "A final cut-off of 1.0 AI was established for the BioPlex 2200 ToRC IgM assay based on an evaluation of 401, 454 and 511 test ordered and retrospective samples for T. gondii, Rubella and CMV IgM, respectively, of which the serological status was determined from the predicate T. gondii, Rubella and CMV IgM assays."
This set of samples, used for cut-off optimization, somewhat resembles a "development set" or "tuning set" in machine learning, though it's integral to the assay's design and calibration rather than a separate training phase.
9. How the Ground Truth for the Training Set Was Established
As noted in point 8, there isn't a "training set" in the AI/ML sense. For the samples used to establish the assay cut-off, the serological status (ground truth) was determined from the predicate T. gondii, Rubella, and CMV IgM assays. This indicates that commercially available and validated assays were used to define the true positive/negative status of these samples for optimizing the new device's cut-off.
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