(254 days)
The BioPlex® 2200 25-OH Vitamin D kit is a flow competitive immunoassay intended for the quantitative determination of 25-hydroxyvitamin D in human serum. The BioPlex 2200 25-OH Vitamin D assay is to be used as an aid in the assessment of vitamin D sufficiency.
The BioPlex® 2200 25-OH Vitamin D kit is intended for use with the Bio-Rad BioPlex 2200 System.
The BioPlex® 2200 25-OH Vitamin D Calibrator Set is intended for the calibration of the BioPlex® 2200 25-OH Vitamin D Reagent Pack.
The BioPlex® 2200 25-OH Vitamin D Control Set is intended for use as an assayed quality control to monitor the overall performance of the BioPlex® 2200 System and the corresponding BioPlex® 25-OH Vitamin D Reagent Packs in the clinical laboratory. The performance of the BioPlex® 25-OH Vitamin D Control Set has not been established with any other 25-hydroxyvitamin D assays.
BioPlex® 2200 25-OH Vitamin D kit includes the following components:
- One (1) 10 mL vial of Bead Set containing dyed beads coated with anti-25-OH D antibody (sheep), an Internal Standard bead (ISB), and a Serum Verification bead (SVB) in buffer with protein stabilizers (bovine). ProClin 950 (
The provided text describes the performance characteristics of the BioPlex® 2200 25-OH Vitamin D Kit, Calibrator Set, and Control Set. This is a medical device, and the information is presented as part of a 510(k) submission to the FDA. The sections below extract the requested information based on the provided document.
Acceptance Criteria and Reported Device Performance
The document does not explicitly state "acceptance criteria" for each performance characteristic. Instead, it presents the results of various studies and implies that these results demonstrate adequate performance for the intended use and substantial equivalence to the predicate device. For precision, for example, it shows the calculated %CV (Coefficient of Variation), which indicates the device's variability. For linearity, it provides the slope, intercept, and r² value of the regression analysis, which are generally expected to be close to 1, 0, and 1, respectively, for good linearity. For interference studies, the implicit acceptance criterion is that the percent difference should be ≤ 10%.
Since explicit acceptance criteria are not provided for all metrics, the table below will list the reported performance and indicate the implicit target where inferable.
| Performance Characteristic | Implicit Acceptance Criteria (Inferred) | Reported Device Performance |
|---|---|---|
| Precision (CLSI EP5-A2) | Low %CVs expected | Total Precision (%CV): |
- Samples: 4.0% - 10.5% (across 6 samples from 15.0 to 110.8 ng/mL)
- Controls: 6.1% - 8.5% (Control 1 at 22.1 ng/mL, Control 2 at 50.0 ng/mL) |
| Reproducibility (CLSI EP15-A2)| Low %CVs expected | Total Precision (%CV): - Samples: 5.0% - 14.8% (across 8 samples from 11.5 to 104.9 ng/mL)
- Controls: 5.1% - 8.5% (Control 1 at 21.6 ng/mL, Control 2 at 58.8 ng/mL) |
| Linearity | Slope ≈ 1, Intercept ≈ 0, r² ≈ 1 | Example: For 168.9 ng/mL, Slope = 1.0001, Intercept = 0.0045, r² = 0.9988 (over dilution range 5.5 - 168.9 ng/mL).
Reportable Measuring Range: 6.5 to 125.0 ng/mL. |
| Detection Limits | Low values for LoB, LoD, LoQ expected | LoB: 0.8 ng/mL
LoD: 2.5 ng/mL
LoQ: 6.5 ng/mL (based on accuracy goal of precision ≤ 20% CV) |
| Interfering Substances | % difference ≤ 10% | No interference observed for tested substances at specified concentrations (e.g., Hemoglobin ≤ 150 mg/dL, Bilirubin (unconjugated) ≤ 20 mg/dL, Triglycerides ≤ 400 mg/dL, etc.), except for Hemoglobin > 150 mg/dL, which "may interfere," and Paricalcitol (Zemplar), which "cross-react[s] and interfere[s]." |
| Cross-Reactivity | Low % cross-reactivity for non-target analytes | High cross-reactivity: 25-hydroxyvitamin D2 (103%), 1,25-dihydroxyvitamin D2 (>100%), 1,25-dihydroxyvitamin D3 (79%), 3-epi 25-hydroxyvitamin D3 (59%).
Low cross-reactivity: Vitamin D2 (0.2%), Vitamin D3 (0.0%), 24,25-dihydroxyvitamin D3 (9%).
Paricalcitol (>100% and interferes). |
| Method Comparison | High correlation (r) and agreement with predicate | Weighted Deming Regression (vs. EUROIMMUN 25-OH Vitamin D ELISA): - N = 196 samples
- Slope = 1.0039 (95% CI: 0.9365 to 1.0712)
- Intercept = -0.2256 (95% CI: -2.4121 to 1.9608)
- Correlation Coefficient (r) = 0.9553 (95% CI: 0.9412 to 0.9661) |
For other requested details:
2. Sample Sizes Used for the Test Set and Data Provenance:
- Precision/Reproducibility (CLSI EP5-A2): 6 frozen human serum samples (N=80 data points for each sample/control for total precision).
- Reproducibility (CLSI EP15-A2): 8 human serum samples (n=20 data points for each sample/control for total precision).
- Linearity: 5 high patient serum samples.
- Detection Limits (LoB): 5 blank samples (100 data points per reagent lot).
- Detection Limits (LoD/LoQ): 6 human samples with low 25-OH vitamin D (60 data points per sample per reagent lot).
- Interfering Substances: Samples containing 10 to 90 ng/mL Vitamin D were used, spiked with various interfering substances.
- Cross-Reactivity: 2 human serum pools (at 20 and 35 ng/mL 25-hydroxyvitamin D), spiked with 9 cross-reactants.
- Method Comparison (CLSI EP09-A2-IR): 204 human samples (185 unaltered, 19 spiked with 25-hydroxyvitamin D3). 196 results included in analysis after excluding 8 out of range samples.
- Expected Values/Reference Range (CLSI C28-A3c): 287 samples from allegedly healthy donors.
- Provenance: Samples were collected from three regions (North, Central, and South) in the US, across spring, summer, and winter, including African Americans, Hispanics, and Caucasians. No specific mention of retrospective or prospective for these samples, but typical for such studies, they are likely collected specifically for the study (prospective) or from a biobank.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:
This document describes an in vitro diagnostic (IVD) device for quantitative measurement of a biomarker. The "ground truth" for the test set is established by the reference method or known concentrations of the analyte.
- For precision, linearity, detection limits, interference, and cross-reactivity studies, the ground truth is based on the known concentrations or analytical characteristics of the spiked samples, dilutions, or control materials. This does not involve human expert interpretation of images or clinical cases. The performance is determined by comparing the device's measurements to these known or expected values.
- For method comparison, the ground truth is the measurement by the predicate device (EUROIMMUN 25-OH Vitamin D ELISA, K123660), which is itself a validated IVD device.
- For expected values/reference range, the "ground truth" is derived from the measurements of samples from a statistically diverse group of healthy individuals, yielding a statistical distribution rather than an expert-defined diagnosis.
Therefore, the concept of "experts establishing ground truth" as it applies to subjective assessments (e.g., radiologists for images) is not directly applicable here.
4. Adjudication Method for the Test Set:
Not applicable in the context of an IVD device for quantitative measurement. The ground truth, where applicable, is either an analytical standard, a predicate device's output, or statistical results from a large sample.
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. This is an IVD device, not an AI-assisted diagnostic imaging device with human readers.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done:
This refers to the "standalone" performance of the BioPlex® 2200 25-OH Vitamin D Kit itself. All the analytical performance studies (precision, linearity, detection limits, interference, cross-reactivity, method comparison) are studies of the device's standalone performance, as it quantifies 25-OH Vitamin D in human serum samples on the Bio-Rad BioPlex 2200 System. The device does not involve a human-in-the-loop for interpretive tasks in the way an AI diagnostic imaging tool would.
7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.):
As indicated in point 3:
- For analytical studies (precision, linearity, detection limits, interference, cross-reactivity), the ground truth is established by analytical standards, known concentrations in spiked samples, or reference materials.
- For method comparison, the ground truth is the measurements obtained from the predicate device.
- For establishing expected values, the "ground truth" is derived from measurements in a defined healthy population.
8. The Sample Size for the Training Set:
The concept of a "training set" typically applies to machine learning or AI models. This document describes a traditional immunoassay system. Therefore, there is no "training set" in the machine learning sense.
However, the closest analogous concept might be the data used for calibration and value assignment.
- Calibrator Assignment: For each calibrator level (except Level 1), three vials were tested in replicates of five on three BioPlex 2200 analyzers for a total of 45 data points to assign values to the kit calibrators using Master calibrators as reference.
- Control Assignment: For each control level, three vials were tested in replicates of five using each of the kit lots on three BioPlex 2200 analyzers, totaling 45 replicates per reagent lot (90 for two lots, 135 for three lots used).
- The "Master calibrators" themselves were derived from internal standards quantified by UV spectrophotometric analysis.
9. How the Ground Truth for the Training Set Was Established:
Again, not a "training set" in the AI sense. For the calibrator and control assignment (analogous to establishing reference values for the system):
- Calibrator Traceability: The BioPlex 25-OH Vitamin D Calibrators are traceable to internal standards that are determined by UV spectrophotometric analysis using the known extinction coefficient of 25-OH Vitamin D at 264 nm wavelength. This is a primary analytical method to establish absolute concentration.
- Master Calibrators: Were manufactured volumetrically from these internal standards into depleted human serum.
- Lot-specific Calibrator and Control Assignment: Performed by testing multiple replicates on multiple analyzers against these Master Calibrators, with mean values having to fall within specified acceptable ranges.
§ 862.1825 Vitamin D test system.
(a)
Identification. A vitamin D test system is a device intended for use in clinical laboratories for the quantitative determination of 25-hydroxyvitamin D (25-OH-D) and other hydroxylated metabolites of vitamin D in serum or plasma to be used in the assessment of vitamin D sufficiency.(b)
Classification. Class II (special controls). Vitamin D test systems must comply with the following special controls:(1) Labeling in conformance with 21 CFR 809.10 and
(2) Compliance with existing standards of the National Committee on Clinical Laboratory Standards.