(307 days)
The Vantera® Clinical Analyzer is an automated laboratory test analyzer which measures the 400 MHz proton nuclear magnetic resonance (NMR) spectrum of clinical samples to produce signal amplitudes, converting these signal amplitudes to analyte concentration. The device includes a 400 MHz NMR spectrometer and software to analyze digitized spectral data. This instrumentation is intended to be used with NMR based assays to detect multiple analytes from clinical samples.
The NMR LipoProfile® test, when used with the Vantera® Clinical Analyzer, an automated NMR spectrometer, measures lipoprotein particles to quantify LDL particle number (LDL-P), HDL cholesterol (HDL-C), and triglycerides in human serum and plasma using nuclear magnetic resonance (NMR) spectroscopy. LDL-P and these NMR-derived concentrations of HDL-C and triglycerides are used in conjunction with other lipid measurements and clinical evaluation to aid in the management of lipoprotein disorders associated with cardiovascular disease.
The Vantera Clinical Analyzer is a clinical laboratory analyzer that employs nuclear magnetic resonance spectroscopic detection to quantify multiple analytes in biological fluid specimens, specifically blood plasma and serum.
The Vantera Clinical Analyzer system design is divided into 3 major subassemblies: a sample handling assembly, an NMR subassembly, and an enclosure. The Vantera Clinical Analyzer control system is distributed across three separate computers:
- The Host (1 U) controls user interface, data handling, results calculation, system startup and shutdown.
- The Process Control (4U) schedules and manages all activities required to process a sample, controls all hardware in the sample handling subsystem.
- The NMR Control Computer controls all magnet operations. Two of these computers are contained within the Sample Handling Subassembly (1 U and 4U) and one in the NMR Subassembly (NMR Console).
The NMR LipoProfile test involves measurement of the 400 MHz proton NMR spectrum of a plasma/serum sample, deconvolution of the composite signal at approximately 0.8 ppm to produce signal amplitudes of the lipoprotein subclasses that contribute to the composite plasma/serum signal, and conversion of these subclass signal amplitudes to Lipoprotein subclass concentrations. The -0.8 ppm plasma NMR signal arises from the methyl group protons of the lipids carried in the LDL, HDL and VLDL subclasses of varying diameters. The NMR signals from the various lipoprotein subclasses have unique and distinctive frequencies and lineshapes, each of which is accounted for in the deconvolution analysis model. Each subclass signal amplitude is proportional to the number of subclass particles emitting the signal, which enables subclass particle concentrations to be calculated from the subclass signal amplitudes derived from the spectral deconvolution analysis. LDL subclass particle concentrations, in units of nanomoles of particles per liter (nmol/L), are summed to give the reported total LDL particle concentration (LDL-P). By employing conversion factors assuming that the various lipoprotein subclass particles have cholesterol and triglyceride contents characteristic of normolipidemic individuals, HDL cholesterol and triglyceride concentrations are also derived.
Here's a breakdown of the acceptance criteria and study information for the Vantera Clinical Analyzer and NMR LipoProfile® test, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document primarily focuses on demonstrating substantial equivalence to a predicate device (K113830) rather than explicitly stating pre-defined "acceptance criteria" for novel performance features. However, the comparisons in the tables serve as the de-facto acceptance criteria: the candidate device's performance must be comparable to or better than the predicate device across various analytical metrics.
| Metric (Analyte) | Predicate Device (K113830) Performance | Candidate Device Performance |
|---|---|---|
| LDL-P (nmol/L) | ||
| Measuring Range | 300 - 3500 | 300-3500 |
| LoB | 0 | 0 |
| LoD | 40.7 | 50.1 |
| LoQ | 132 | 154.7 |
| Linearity Regression | y= 1.02x + 7.82 | y= 0.99x + 106.6 |
| Linearity R² | 0.995 | 0.997 |
| Linear Range | 225 - 4322 | 290 - 3524 |
| Within-Run Precision (CV%) | Level 1: 5.8, Level 2: 3.0, Level 3: 2.7 | Level 1: 7.7, Level 2: 5.5, Level 3: 2.6 |
| Within-Lab Precision (CV%) | Level 1: 5.3, Level 2: 4.0, Level 3: 3.9 | Level 1: 7.0, Level 2: 6.8, Level 3: 2.7 |
| Method Comparison | Linear regression: y=1.03x - 36.60, r=0.978 | Deming fit: y= 43.44 + 0.98x r = 0.988 |
| Medical Decision Limits | 1000, 1300 and 1600 | same |
| Sample Type | Serum and Plasma | same |
| Carryover | No significant trending of results and no persistent bias | same |
| Interference Study | Salicylic acid at ≥ 1.3mmol/L, Clopidogrel hydrogensulfate at ≥ 95.7 µmol/L | Clopidogrel (Plavix) at 95.7 µmol/L, Salicylic acid at 1.3 mmol/L, Fenofibrate at 31 µmol/L, Menhaden oil at 0.6 mg/mL. (Note: Candidate device lists more interferences than predicate for LDL-P) |
| TG (mg/dL) | ||
| Measuring Range | 5- 1100 | 10 - 1100 |
| LoB | 1.1 | 1.2 |
| LoD | 2.3 | 2.3 |
| LoQ | 4 | 4.8 |
| Linearity Regression | $y= 1.01x - 0.40$ | $y= 1.01x - 1.7$ |
| Linearity R² | 1.0 | 1.0 |
| Linear Range | 4 - 1346 | 4 - 1355 |
| Within-Run Precision (CV%) | Level 1: 2.3, Level 2: 2.1, Level 3: 1.2 | Level 1: 2.7, Level 2: 0.9, Level 3: 0.6 |
| Within-Lab Precision (CV%) | Level 1: 2.3, Level 2: 2.4, Level 3: 2.7 | Level 1: 3.3, Level 2: 1.5, Level 3: 2.5 |
| Method Comparison | Linear regression: $y=1.00x + 0.92, r=0.998$ | Deming fit: $Y= 1.01x +0.30 r=1.00$ |
| Sample Type | Serum and Plasma | same |
| Carryover | No significant trending of results and no persistent bias | same |
| Interference Study | 7 Endogenous and 23 Exogenous substances tested, no interference found | same (no interference found with 7 Endogenous and 23 Exogenous substances) |
| HDL-C (mg/dL) | ||
| Measuring Range | 7 - 140 | 7 - 140 |
| LoB | 2.7 | 3.2 |
| LoD | 3.5 | 4.4 |
| LoQ | 4 | 4.4 |
| Linearity Regression | $y= 1.04x - 0.35$ | $y= 1.02x - 0.63$ |
| Linearity R² | 1.0 | 1.0 |
| Linear Range | 6 - 148 | 5 - 168 |
| Within-Run Precision (CV%) | Level 1: 4.0, Level 2: 2.8, Level 3: 2.6 | Level 1: 1.5, Level 2: 0.7, Level 3: 1.8 |
| Within-Lab Precision (CV%) | Level 1: 2.8, Level 2: 2.0, Level 3: 1.8 | Level 1: 2.7, Level 2: 1.9, Level 3: 2.9 |
| Method Comparison | Linear regression: $y=1.04x-1.20, r=0.989$ | Deming fit: $y= -1.36 + 1.01x - r=0.998$ |
| Sample Type | Serum and Plasma | same |
| Carryover | No significant trending of results and no persistent bias | same |
| Interference Study | 7 Endogenous and 23 Exogenous substances tested, no interference found | same (no interference found with 7 Endogenous and 23 Exogenous substances) |
2. Sample Size and Data Provenance for the Test Set
The document does not explicitly state the specific sample sizes for each analytical validation study for the "test set" in terms of number of patient samples. It mentions "Level 1, Level 2, Level 3" for precision studies, implying control samples at different concentrations. For linearity, there are ranges of values. For the method comparison, it gives regression parameters, which typically require a reasonable number of samples, but the exact count isn't specified.
The data provenance (country of origin, retrospective/prospective) is not provided in the document.
3. Number of Experts and Qualifications for Ground Truth of Test Set
This information is not applicable and not provided. The device (Vantera Clinical Analyzer with NMR LipoProfile® test) is an IVD for quantitative measurement of lipoprotein particles, HDL cholesterol, and triglycerides. The ground truth for these measurements in analytical validation studies would typically be established by:
- Reference methods (e.g., ultracentrifugation for lipoproteins, enzymatic assays for cholesterol/triglycerides).
- Certified reference materials.
- Highly qualified laboratory personnel following established protocols for the reference methods.
Experts in the sense of clinical reviewers (e.g., radiologists for imaging devices) are not typically involved in establishing ground truth for this type of analytical device.
4. Adjudication Method for the Test Set
Not applicable. This is not a human interpretation-based diagnostic device requiring adjudication of expert opinions.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
Not applicable. This is an automated analytical laboratory device, not an imaging or interpretation aid for human readers. Therefore, an MRMC study and effects of AI assistance on human readers are not relevant.
6. Standalone Performance Study
Yes, the studies presented are standalone (algorithm only) performance studies. The results in the tables (Measuring Range, LoB, LoD, LoQ, Linearity, Precision, Method Comparison, Carryover, Interference) directly reflect the performance of the Vantera Clinical Analyzer and NMR LipoProfile® test itself, without any human-in-the-loop interaction for interpretation, beyond the standard operation of an automated laboratory instrument.
7. Type of Ground Truth Used
The ground truth for the analytical validation studies would be established using reference methods or reference materials. For example:
- Method Comparison: Comparison against a recognized reference method for lipoprotein quantification, HDL-C, and triglycerides. While not explicitly stated, standard practice would involve a comparison to a well-characterized, clinically accepted method. The "Deming fit" and "Linear regression" indicate comparison to another quantitative measurement.
- Linearity, LoB, LoD, LoQ: These are typically established using characterized control materials (known concentrations) or serial dilutions of patient samples.
- Precision: Established using control materials at different concentrations.
8. Sample Size for the Training Set
The document does not specify a separate "training set" or its size. This device is an analytical instrument based on Nuclear Magnetic Resonance (NMR) spectroscopy and a deconvolution analysis model. While the deconvolution model itself would have been developed and "trained" or optimized using a dataset of known NMR spectra and corresponding reference measurements, the document focuses on the validation of the integrated device. The details of the dataset used for the initial development/training of the deconvolution algorithm are not provided here.
9. How the Ground Truth for the Training Set Was Established
As above, the document does not provide details on the training set for the deconvolution model. However, for a device based on a physical principle like NMR spectroscopy, the ground truth for establishing the deconvolution model and conversion factors would likely involve:
- Carefully characterized samples with known concentrations of lipoproteins, HDL-C, and triglycerides, determined by highly accurate reference methods (e.g., ultracentrifugation for lipoprotein subfractions, established enzymatic methods for cholesterol and triglycerides).
- Spectral data from these characterized samples would be used to build and optimize the deconvolution algorithm (i.e., establish unique frequencies and lineshapes) and the conversion factors from signal amplitudes to concentrations.
§ 862.2570 Instrumentation for clinical multiplex test systems.
(a)
Identification. Instrumentation for clinical multiplex test systems is a device intended to measure and sort multiple signals generated by an assay from a clinical sample. This instrumentation is used with a specific assay to measure multiple similar analytes that establish a single indicator to aid in diagnosis. Such instrumentation may be compatible with more than one specific assay. The device includes a signal reader unit, and may also integrate reagent handling, hybridization, washing, dedicated instrument control, and other hardware components, as well as raw data storage mechanisms, data acquisition software, and software to process detected signals.(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9. The special control is FDA's guidance document entitled “Class II Special Controls Guidance Document: Instrumentation for Clinical Multiplex Test Systems.” See § 862.1(d) for the availability of this guidance document.