(247 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 (1U) 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, and manages remote access to the system. The NMR Control Computer controls all magnet operations. Two of these computers are contained within the Sample Handling Subassembly (1U 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 provided 510(k) summary focuses on the analytical performance of the Vantera® Clinical Analyzer and the NMR LipoProfile® test compared to predicate devices, establishing substantial equivalence rather than providing explicit acceptance criteria as would be typical for a novel device. The study described primarily demonstrates that the proposed device performs comparably to its predicate devices in terms of analytical accuracy and precision.
Here's an analysis of the acceptance criteria and study information provided:
1. A table of acceptance criteria and the reported device performance
The document does not explicitly state acceptance criteria in a pass/fail format. Instead, it demonstrates performance by comparing the analytical results of the Vantera® Clinical Analyzer with the NMR LipoProfile® test to its predicate device (NMR Profiler for the assay) across various metrics. The unstated acceptance criteria for each analytical performance metric would be that the proposed device's performance must be comparable to or better than the predicate device's performance.
| Metric | Acceptance Criteria (Implied) | Reported Proposed Device Performance (Vantera® Clinical Analyzer) | Predicate Device Performance (NMR Profiler) |
|---|---|---|---|
| LDL-P | |||
| LoB | Comparable to predicate | 0 nmol/L | 0 nmol/L |
| LoD | Comparable to predicate | 40.7 nmol/L | 41 nmol/L |
| LoQ | Comparable to predicate | 132 nmol/L | 157 nmol/L |
| Measuring Range | Comparable to predicate | 300-3500 nmol/L | 300-3500 nmol/L |
| Linearity Regression (Y=mX+b) | R² comparable to predicate | y=1.02x+7.82, R²=0.9949 | y=0.99x-22.37, R²=0.9979 |
| Within-Run Precision (CV%) | Comparable to predicate | Level 1: 5.8%, Level 2: 3.0%, Level 3: 2.7% | Level 1: 5.0%, Level 2: 4.3%, Level 3: 3.7% |
| Within-Lab Precision (CV%) | Comparable to predicate | Level 1: 5.3%, Level 2: 4.0%, Level 3: 3.9% | Level 1: 7.6%, Level 2: 4.5%, Level 3: 4.3% |
| Method Comparison (Correlation R) | Comparable to predicate | R=0.978 | R=0.973 |
| Interference Study | No significant interference for tested substances | Salicylic acid (≥ 1.3mmol/L) and Clopidogrel hydrogensulfate (≥ 95.7 µmol/L) determined to interfere. | No interference found for 5 endogenous & 22 exogenous substances. |
| Specimen Stability (Refrigerated) | Comparable to predicate | 6 days | 5 days |
| Triglycerides | |||
| LoB | Comparable to predicate | 1.1 mg/dL | 1.4 mg/dL |
| LoD | Comparable to predicate | 2.4 mg/dL | 2.6 mg/dL |
| LoQ | Comparable to predicate | 4 mg/dL | 2.6 mg/dL |
| Measuring Range | Comparable to predicate | 5-1100 mg/dL | 5-1100 mg/dL |
| Linearity Regression (Y=mX+b) | R² comparable to predicate | y=1.008x-0.3979, R²=0.9999 | y=0.95x-12.21, R²=0.999 |
| Within-Run Precision (CV%) | Comparable to predicate | Level 1: 2.3%, Level 2: 2.1%, Level 3: 1.2% | Level 1: 2.6%, Level 2: 1.8%, Level 3: 1.3% |
| Within-Lab Precision (CV%) | Comparable to predicate | Level 1: 2.3%, Level 2: 2.4%, Level 3: 2.7% | Level 1: 3.6%, Level 2: 2.6%, Level 3: 2.5% |
| Method Comparison (Correlation R) | Comparable to predicate | R=0.998 | R=1.00 |
| Interference Study | No significant interference for tested substances | No interference found for 7 endogenous & 23 exogenous substances. | Ibuprofen may interfere with TG measurement at and above 210µg/mL for 5 endogenous & 22 exogenous substances. |
| Specimen Stability (Refrigerated) | Comparable to predicate | 6 days | 10 days |
| HDL-C | |||
| LoB | Comparable to predicate | 2.7 mg/dL | 4.3 mg/dL |
| LoD | Comparable to predicate | 3.5 mg/dL | 5.2 mg/dL |
| LoQ | Comparable to predicate | 4 mg/dL | 5.2 mg/dL |
| Measuring Range | Comparable to predicate | 7-140 mg/dL | 7-140 mg/dL |
| Linearity Regression (Y=mX+b) | R² comparable to predicate | y=1.049x-0.3459, R²=0.9961 | y=1.004x-0.5956, R²=0.9998 |
| Within-Run Precision (CV%) | Comparable to predicate | Level 1: 4.0%, Level 2: 2.8%, Level 3: 2.6% | Level 1: 2.0%, Level 2: 1.9%, Level 3: 0.9% |
| Within-Lab Precision (CV%) | Comparable to predicate | Level 1: 2.8%, Level 2: 2.0%, Level 3: 1.8% | Level 1: 3.3%, Level 2: 2.0%, Level 3: 1.8% |
| Method Comparison (Correlation R) | Comparable to predicate | R=0.989 | R=0.999 |
| Interference Study | No significant interference for tested substances | No interference found for 7 endogenous & 23 exogenous substances. | No interference found for 5 endogenous & 22 exogenous substances. |
| Specimen Stability (Refrigerated) | Comparable to predicate | 6 days | 10 days |
Study Proving Acceptance Criteria:
The study conducted was an analytical validation comparing the performance of the Vantera® Clinical Analyzer with the NMR LipoProfile® test to its predicate device (NMR Profiler for the assay) across various analytical parameters. The overall conclusion is that the new device is "as safe and effective as its predicate device."
2. Sample size used for the test set and the data provenance
- Test Sets (Analytical Studies):
- Analytical Sensitivity (LoB, LoD, LoQ): Five serum pools for low concentrations tested in replicates of 4 for 3 days. Non-lipoprotein specimens analyzed 60 consecutive times for 3 days for LoB.
- Assay Precision (Within-run & Within-Laboratory): 20 replicates of three patient serum pools in the same run and in 20 different runs over 20 days. Reproducibility study used 5 levels of serum panels tested for 5 days, 6 runs per day, 2 replicates per run at 3 sites (n=60 per panel per site, total N=177-180 across all sites for each panel).
- Linearity: Three serum pools prepared from patient specimens mixed and diluted to produce eleven (for LDL-P) or twelve (for TG and HDL-C) different samples, with four replicates of each pool analyzed.
- Method Comparison:
- LDL-P: n=1483 serum samples.
- HDL-C: n=1518 serum samples.
- Triglycerides: n=1520 serum samples.
- Interfering Substances: 7 endogenous agents and 23 drugs were screened.
- Reference Range: Serum samples (n=452) from apparently healthy men (n=158) and women (n=294).
- Data Provenance: The document does not specify the country of origin. The studies were described as "analytical validations" and included testing using "patient specimens" and "serum pools." There is no explicit mention of the data being either retrospective or prospective, but the nature of the analytical studies suggests controlled laboratory environments rather than a large-scale clinical trial with patient follow-up. For the reference range, it states "serum samples... were analyzed from apparently healthy men and women," which implies a prospective collection for this specific purpose or a well-characterized existing cohort. The MESA (Multi-Ethnic Study of Atherosclerosis) is mentioned for the predicate device's reference range, suggesting a US context for that, but it's not explicitly stated for the proposed device's reference population.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
The document does not describe the use of human experts to establish "ground truth" for the test set in the context of interpretation or diagnosis. This device is an automated laboratory analyzer for quantifying analytes. The "ground truth" for its analytical performance studies (e.g., precision, linearity, method comparison) is established by comparing its measurements to a reference method or known concentrations, or by assessing consistency internally.
4. Adjudication method for the test set
Not applicable. There was no clinical study involving human interpretation or diagnosis that would require an adjudication method. The testing involved direct analytical measurements.
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 in-vitro diagnostic (IVD) device for quantifying analytes (LDL-P, HDL-C, Triglycerides), not an AI-assisted diagnostic imaging or interpretation device that would involve human readers.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the primary performance studies presented are "standalone" in the sense that they assess the device's analytical performance (algorithm + instrument) in quantifying the specified analytes without human-in-the-loop performance for diagnosis or interpretation. The device's output is explicit numerical analyte concentrations.
7. The type of ground truth used
The ground truth used for verifying the analytical performance of the device was:
- Reference Methods/Known Concentrations: For analytical sensitivity (LoB, LoD, LoQ), linearity, and precision, the "ground truth" was established through precisely prepared serum pools and non-lipoprotein specimens with known or target concentrations, or through statistical determination methods (e.g., EP17-A).
- Comparison to Predicate Device: For method comparison studies, the "ground truth" or reference was the measurements obtained from the legally marketed predicate device (NMR Profiler) using patient samples. The goal was to show high correlation and similar results between the two devices.
- CLSI Guidelines: Standardized guidelines (e.g., EP5-A2, EP6-A, EP7-A2, EP9-A2, EP17-A) from the Clinical and Laboratory Standards Institute (CLSI) were referenced for establishing protocols for these analytical validations.
8. The sample size for the training set
The document does not explicitly mention a "training set" in the context of machine learning or AI models. This device is an automated NMR spectrometer that measures signals and converts them to concentrations based on specified deconvolution analysis models. The development of these deconvolution models would have involved a form of "training" or optimization, but the document does not detail the dataset size or methodology used for this prior model development. The document focuses on the analytical validation of the manufactured device.
9. How the ground truth for the training set was established
As there is no explicit mention of a "training set" in the conventional AI/ML sense, this question cannot be directly answered from the provided text. However, the assay description mentions:
"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."
This suggests that the deconvolution analysis model was developed using a "ground truth" based on the established biophysical properties of lipoprotein subclasses and their NMR spectral characteristics. This likely involved:
- Carefully characterized lipoprotein samples with known subclass concentrations.
- Expert knowledge of NMR spectroscopy and signal processing.
- Calibration against established reference methods for lipoprotein analysis.
The document does not provide details on the specific data sets or expert consensus used for the initial development and establishment of this deconvolution model.
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510(k) Summary
-
LIPOSCIENCE
A. -
KIL3830 510(k) Number:
AUG
30
2012
B. Submitter Contact Information:
Submitter:
LipoScience, Inc. 2500 Sumner Boulevard Raleigh, NC 27616 Ph: (919) 256-1326 Fax: (919) 256-1149
Contact Person:
Suzette Warner Manager, Regulatory Affairs LipoScience, Inc. Ph: (919) 256-1326 Fax: (919) 256-1149 Suzette. Warner@liposcience.com
C. Device Name:
Vantera® Clinical Analyzer Trade Name: NMR LipoProfile® test on Vantera® Clinical Analyzer Common Name: Classification Names:
Instrumentation for clinical multiplex test system, 21 CFR 862.2570, Product Code NSU Lipoprotein test system, 21 CFR 862.1475, Product Code MRR and LBS Cholesterol test system 21 CFR 862.1175, Product Code LBS Triglyceride test system, 21 CFR 862.1705, Product Code CDT
Clinical Chemistry (75) Panel:
Legally Marketed Device to which Equivalence is Claimed (Predicate Device): D.
| NMR Profiler and NMR Lipoprofile test | K111516 |
|---|---|
| Luminex LX 100/200 Instrument | K073506 |
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E. Device Description:
For the Instrument
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 (1U) 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, and manages remote access to the system.
- . The NMR Control Computer controls all magnet operations.
Two of these computers are contained within the Sample Handling Subassembly (1U and 4U) and one in the NMR Subassembly (NMR Console).
For the Assay
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.
F. Indications for Use
For the Instrument
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
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spectral data. This instrumentation is intended to be used with NMR based assays to detect multiple analytes from clinical samples by technologists trained in laboratory techniques, procedures and on the use of the analyzer.
For the Assay
The NMR LipoProfiletest, 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.
G. Technological Characteristics and Substantial Equivalence:
The Vantera Clinical Analyzer is as safe and effective as the predicate device, K073506. The Vantera has similar intended use and indication for use as well as the same multianalyte capability and the same system calibration requirement as the predicate device. The minor technological differences between the Vantera and the predicate device raise no new issues of safety or effectiveness.
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| Instrument Comparison Table | ||
|---|---|---|
| -- | ----------------------------- | -- |
| Luminex LX 100/200Instrument(Predicate) | Vantera Clinical Analyzer(Proposed Device) | |
|---|---|---|
| 510(k)Number | K073506 | Pending |
| Intended Use /Indications forUse | The Luminex LX100/200 Instrument is aclinical multiplex testsystem intended tomeasure and sort multiplesignals generated in an InVitro diagnostic assayfrom a clinical sample.This instrumentation isused with a specific assayto measure multiplesimilar analytes thatestablish a singleindicator to aid indiagnosis. The deviceincludes a signal readerunit, raw data storagemechanisms, dataacquisition software andsoftware to processdetected signals. | similar |
| Technology | Bead based multiplexing | Nuclear magneticresonance |
| Multi-Analyte | Yes | same |
| DetectionMethod | Fluorescent | 400 MHz proton NMRSpectrum |
| SystemFluidics | Utilizes system fluidics todeliver sample to the siteof sample analysis | same |
| SpecimenSampling andHandling | Samples are manuallyprepared then presented tosystem. | Serum/Plasma Samples arediluted onboard system |
| SystemCalibration | System calibrationrequired | same |
| Luminex LX 100/200Instrument(Predicate) | Vantera Clinical Analyzer(Proposed Device) | |
| QualityControlChecks | System level qualitycontrol checks availablee.g. Classification (CONI)and reporter (CONII) | similarE.g. Signal to noise ratio –internal system check thatoccur during systemcalibration |
| SpecimenIdentification | Barcode reader entry ofsample ID | same |
| DataAcquisitionSoftware | Posses data acquisitionsoftware and software toprocess detected signals | same |
·
...
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Similarity to the Predicate Device (Assay)
Performance data further demonstrate that the Vantera Clinical Analyzer when used with the NMR LipoProfile test is as safe and effective as its predicate device, K111516. As with the predicate test, the NMR LipoProfile test on Vantera is intended for the separation and quantification of LDL-P, HDL-C and triglycerides in serum and plasma, measurements of which are used in conjunction with other lipid measurements and clinical evaluation to aid in the management of lipoprotein disorders associated with cardiovascular disease.
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| LipoScienceNMR LipoProfile® testand NMR Profiler(Predicate) | Vantera® ClinicalAnalyzer for use withNMR LipoProfile® test(Proposed Device) | |
|---|---|---|
| 510(k)Number | K111516 | Pending |
| Intended Use /Indications forUse | The NMR LipoProfile®test, used with the NMRProfiler, an automatednuclear magneticresonance (NMR)spectrometer, measureslipoprotein particles toquantify LDL particlenumber (LDL-P), HDLcholesterol (HDL-C), andtriglycerides in serumand plasma using NMRspectroscopy. LDL-Pand these NMR-derivedconcentrations oftriglycerides and HDL-Care used in conjunctionwith other lipidmeasurements andclinical evaluation to aidin the management oflipoprotein disordersassociated withcardiovascular disease.This test is performedand provided as a serviceby LipoScienceLaboratory. | similar |
| PatientPopulation | General | same |
| InstrumentPlatform | NMR Profiler | Vantera Clinical Analyzer |
| SpecimenAnalyzer | Human serum and plasma | same |
| 400 MHz NMRSpectrometer | same | |
| LipoScienceNMR LipoProfile® testand NMR Profiler(Predicate) | Vantera® ClinicalAnalyzer for use withNMR LipoProfile® test(Proposed Device) | |
| Reagents andMaterials | NMR Diluent 1 - aqueous solution containing Na2EDTA (5.0mM), CaCl2 (1.0mM), KCL(120mM), Na2HPO4-7H20(50mM), (50mM), pH 7.4, 6.0 M NaOH, 1.0 M HCl. NMR WASH - Triton X-100-0.1%v/v, Liqui Nox 0.1% v/v in Type 2 water, pH 10.0, sodium bicarbonate (anhydrous), sodium carbonate (anhydrous), 6.0 M NaOH NMR Calibrator - aqueous solution of Trimethyl Acetate (TMA) disodium salt (15.0 mM) containing Na2EDTA (5.0 mM), CaC2 (3.0 mM), KCl (120 nM), D2O 10% v/v NMR LipoProfile Quality Control materials 1 and 2 contains two levels of pooled human serum-based control material, labeled Control 1 and Control 2, with pre-determined target ranges, containing sodium azide as a preservative. | Similar |
| LipoScienceNMR LipoProfile® testand NMR Profiler(Predicate) | Vantera® ClinicalAnalyzer for use withNMR LipoProfile® test(Proposed Device) | |
| SpectralDeconvolutionComputationalProcess | Linear least-squareswith singular valuedecomposition of thespectra from eachspecimen. | Same |
| ReferenceRange | Distribution of LDL-PObserved in Referencepopulation - MESA | Distribution of LDL-Pobserved in a generalapparently healthypopulation of men andwomen |
Assay General Attributes
.
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We performed analytical validations to demonstrate that the NMR LipoProfile® test on the Vantera Clinical Analyzer is equivalent to the NMR LipoProfile® test on the NMR Profiler. The comparative analytical performance is found in tables below.
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Vantera® Clinical Analyzer for use with NMR LipoProfile® test Premarket Notification 510(k) Section 6 -- 510(k) Summary
| LDL-P (nmol/L) | Vantera clinical analyzerfor use with theNMR LipoProfile test | Predicate Device K111516 | ||||
|---|---|---|---|---|---|---|
| LoB | 0 | 0 | ||||
| LoD | 40.7 | 41 | ||||
| LoQ | 132 | 157 | ||||
| Measuring Range | 300-3500 nmol/L | 300-3500 nmol/L | ||||
| Linearity Regression | y=1.02x+7.82 | y=0.99x-22.37 | ||||
| Linearity R² | 0.9949 | 0.9979 | ||||
| Within-Run Precision | Level 1 | Level 2 | Level 3 | Level 1 | Level 2 | Level 3 |
| Mean | 842.6 | 1309.5 | 1837.7 | 908 | 1493 | 1967 |
| SD | 48.5 | 39.1 | 50.3 | 45.4 | 64.8 | 72.8 |
| CV% | 5.8% | 3.0% | 2.7% | 5.0% | 4.3% | 3.7% |
| Within-Lab Precision | Level 1 | Level 2 | Level 3 | Level 1 | Level 2 | Level 3 |
| Mean | 988.6 | 1266.7 | 1943.5 | 920.4 | 1508.3 | 1991.8 |
| SD | 48.84 | 32.57 | 63.42 | 70.5 | 67.7 | 84.6 |
| CV% | 5.3% | 4.0% | 3.9% | 7.6% | 4.5% | 4.3% |
| Method Comparison | Linear regression:y=1.03x-36.60, R=0.978 | Linearity Regression:y=0.98x+45.2, R=0.973 | ||||
| Medical Decision Limits | No change. | 1000, 1300 and 1600 nmol/L | ||||
| Interference Study | 7 Endogenous and 23 Exogenous weretested. Salicyclic acid at ≥ 1.3mmol/Lwas determined to interfere with LDL-P and Clopidogrel hydrogensulfate at≥ 95.7 µmol/L was determined tointerfere with LDL-P | 5 Endogenous and 22 Exogenouswere tested, no interference wasfound. | ||||
| Specimen Stability | Lipotube:Refrigerated Stability: 6 days | Lipotube:Refrigerated Stability: 5 days |
Analytical Performance for LDL-P
.
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| Triglycerides Analytical Performance Summary | ||||||
|---|---|---|---|---|---|---|
| Vantera clinical analyzerfor use with theNMR LipoProfile test | Predicate Device K111516 | |||||
| TG (mg/dL) | LoB | 1.1 | 1.4 | |||
| LoD | 2.4 | 2.6 | ||||
| LoQ | 4 | 2.6 | ||||
| Measuring Range | 5 | 1100 | ||||
| Linearity Regression | y=1.008x-0.3979 | y=0.95x-12.21 | ||||
| Linearity R2 | 0.9999 | 0.999 | ||||
| Within-Run Precision | Level 1 | Level 2 | Level 3 | Level 1 | Level 2 | Level 3 |
| Mean | 70.1 | 169.2 | 356.1 | 81.0 | 140.6 | 649.5 |
| SD | 1.6 | 3.5 | 4.2 | 2.1 | 2.5 | 8.7 |
| CV% | 2.3% | 2.1% | 1.2% | 2.6% | 1.8% | 1.3% |
| Within-Lab Precision | Level 1 | Level 2 | Level 3 | Level 1 | Level 2 | Level 3 |
| Mean | 68.8 | 166.3 | 352.2 | 78.4 | 145.4 | 624.6 |
| SD | 1.59 | 3.92 | 9.36 | 2.8 | 3.7 | 15.4 |
| CV% | 2.3% | 2.4% | 2.7% | 3.6% | 2.6% | 2.5% |
| Method Comparison | Linear regression:y=1.00x+0.92, R=0.998 | Linear regression:y=1.00x+1.25, R=1.00 | ||||
| Medical Decision Limits | No change. | Normal (<150)Borderline-High (150-199)High (200-499)Very High (≥500) | ||||
| Interference Study | 7 Endogenous and 23 Exogenous weretested, no interference was found. | 5 Endogenous and 22 Exogenouswere tested, no interference wasfound except Ibuprofen may interferewith TG measurement at and above210µg/mL. | ||||
| Specimen Stability | Lipotube:Refrigerated Stability: 6 days | Lipotube:Refrigerated Stability: 10 days |
Triglycerides Analytical Performance Summary
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| HDL-C (mg/dL) | Vantera clinical analyzer for use with the NMR LipoProfile test | Predicate Device K111516 | ||||
|---|---|---|---|---|---|---|
| LoB | 2.7 | 4.3 | ||||
| LoD | 3.5 | 5.2 | ||||
| LoQ | 4 | 5.2 | ||||
| Measuring Range | 7-140 | 7-140 | ||||
| Linearity Regression | y=1.049x-0.3459 | y=1.004x-0.5956 | ||||
| Linearity R2 | 0.9961 | 0.9998 | ||||
| Within-Run Precision | Level 1 | Level 2 | Level 3 | Level 1 | Level 2 | Level 3 |
| Mean | 29.1 | 51.1 | 86.9 | 23.7 | 54.9 | 95.1 |
| SD | 1.17 | 1.43 | 2.29 | 0.5 | 1.0 | 0.9 |
| CV% | 4.0% | 2.8% | 2.6% | 2.0% | 1.9% | 0.9% |
| Within-Lab Precision | Level 1 | Level 2 | Level 3 | Level 1 | Level 2 | Level 3 |
| Mean | 28.9 | 50.7 | 85.2 | 23.7 | 56.7 | 96.1 |
| SD | 0.80 | 1.02 | 1.51 | 0.8 | 1.1 | 1.7 |
| CV% | 2.8% | 2.0% | 1.8% | 3.3% | 2.0% | 1.8% |
| Method Comparison | Linear regression:y=1.04x-1.20, R=0.989 | Linear regression:y=1.00x+0.03, R=0.999 | ||||
| Medical Decision Limits | No change. | Low(<40),High(≥60) | ||||
| Interference Study | 7 Endogenous and 23 Exogenous were tested, no interference was found. | 5 Endogenous and 22 Exogenous were tested, no interference was found. | ||||
| Specimen Stability | Lipotube:Refrigerated Stability: 6 days | Lipotube:Refrigerated Stability: 10 days |
HDL-C Analytical Performance Summary
.
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Performance Data - Non-Clinical: H.
Analytical Sensitivity
The analytical sensitivity of the NMR LipoProfile test measurements of LDL-P, HDL-C, and triglycerides was determined as the lowest concentration measurable with acceptable precision and accuracy. Limits of quantification (LoQ), Limit of Blank (LoB) and Limit of Detection (LoD) for LDL-P, HDL-C and Triglycerides following EP17-A are listed
LDL-P
Five serum pools containing very low concentration were tested in replicates of 4 for 3 days. The Limit of Quantification (LoQ) was mathematically calculated for LDL-P by plotting the %CV on the Y-axis against low concentration pools and determined to be: LoO = 132 nmol/L.
Non-lipoprotein specimens were analyzed 60 consecutive times for 3 days. The Limit of Blank (LoB) was calculated non-parametrically for LDL-P and determined to be: LoB = 0.0 nmol/L.
Five serum pools containing very low concentration were tested in replicates of 4 for 3 davs. The Limit of Detection (LoD) was calculated parametrically for LDL-P and determined to be: LoD = 40.7 nmol/L.
HDL-C
Five serum pools containing very low concentration were tested in replicates of 4 for 3 days. The Limit of Quantification (LoQ) was mathematically calculated for HDL-C by plotting the %CV on the Y-axis against low concentration pools and determined to be: LoO = 4 mg/dL.
Non-lipoprotein specimens were analyzed 60 consecutive times for 3 days. The Limit of Blank (LoB) was calculated non-parametrically for HDL-C and determined to be: LoB = 2.7 mg/dL.
Five serum pools containing very low concentration were tested in replicates of 4 for 3 days. The Limit of Detection (LoD) was calculated parametrically for HDL-C and determined to be: LoD = 3.5 mg/dL.
Triglycerides
Five serum pools containing very low concentration were tested in replicates of 4 for 3 days. The Limit of Quantification (LoQ) was mathematically calculated for Triglycerides by plotting the %CV on the Y-axis against low concentration pools and determined to be: LoQ = 4 mg/dL.
Non-lipoprotein specimens were analyzed 60 consecutive times for 3 days. The Limit of Blank (LoB) was calculated non-parametrically for Triglycerides and determined to be: LoB = 1.1 mg/dL.
Five serum pools containing very low concentration were tested in replicates of 4 for 3 days. The Limit of Detection (LoD) was calculated parametrically for Triglycerides and determined to be: LoD = 2.4 mg/dL.
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Assay Precision
Within-run precision and within-laboratory precision were determined by testing 20 replicates of three patient serum pools in the same run and in 20 different runs over 20 days. The pools were analyzed according to EP-5A. The results of this testing are summarized below:
Within-run Precision (n=20)
| Pool #1 | Pool #2 | Pool #3 | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Mean | SD | %CV | Mean | SD | %CV | Mean | SD | %CV | |
| LDL-P,nmol/L | 842.6 | 48.5 | 5.8 | 1309.5 | 39.1 | 3.0 | 1837.7 | 50.3 | 2.7 |
| HDL-C,mg/dL | 29.1 | 1.17 | 4.0 | 51.1 | 1.43 | 2.8 | 86.9 | 2.29 | 2.6 |
| Triglycerides,mg/dL | 70.1 | 1.6 | 2.3 | 169.2 | 3.5 | 2.1 | 356.1 | 4.2 | 1.2 |
Within-Laboratory Precision (n=80)
| Pool #1 | Pool #2 | Pool #3 | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Mean | SD | %CV | Mean | SD | %CV | Mean | SD | %CV | |
| LDL-P,nmol/L | 988.6 | 52.20 | 5.3 | 1266.7 | 50.08 | 4.0 | 1943.5 | 75.11 | 3.9 |
| HDL-C,mg/dL | 28.9 | 0.80 | 2.8 | 50.7 | 1.02 | 2.0 | 85.2 | 1.51 | 1.8 |
| Triglycerides,mg/dL | 68.8 | 1.59 | 2.3 | 166.3 | 3.92 | 2.4 | 352.2 | 9.36 | 2.7 |
Reproducibility
A reproducibility study was conducted in accordance to EPS-A2 at 3 sites incorporating five levels of serum panels at or around the medical decision limits. The panels were tested for 5 days, 6 runs per day, 2 replicates per run. The overall precision estimates are described below.
{13}------------------------------------------------
| LDL-P (nmol/L) | |||||
|---|---|---|---|---|---|
| Pool # | 1 | 11 | 7 | 3 | 9 |
| NMR 8001 | Panel 1 | Panel 2 | Panel 3 | Panel 4 | Panel 5 |
| Mean (nmol/L) | 513.4 | 1129.4 | 1361.6 | 1957.7 | 3286.5 |
| n | 60 | 60 | 60 | 59 | 60 |
| SD (nmol/L) | 32.86 | 65.60 | 87.36 | 103.55 | 197.94 |
| CV (%) | 6.4 | 5.8 | 6.4 | 5.3 | 6.0 |
| min (nmol/L) | 431 | 988 | 1163 | 1641 | 2938 |
| max (nmol/L) | 573 | 1318 | 1510 | 2179 | 3636 |
| median (nmol/L) | 517 | 1127 | 1380.5 | 1962 | 3288.5 |
| NMR 8002 | Panel 1 | Panel 2 | Panel 3 | Panel 4 | Panel 5 |
| Mean (nmol/L) | 566.7 | 1260.6 | 1364.5 | 2050.7 | 3204.7 |
| n | 59 | 60 | 59 | 59 | 60 |
| SD (nmol/L) | 39.22 | 38.00 | 76.99 | 65.41 | 85.41 |
| CV (%) | 6.9 | 3.0 | 5.6 | 3.2 | 2.7 |
| min (nmol/L) | 457 | 1168 | 1155 | 1843 | 3036 |
| max (nmol/L) | 660 | 1346 | 1555 | 2176 | 3419 |
| median (nmol/L) | 574 | 1258.5 | 1366 | 2050 | 3197 |
| NMR 8003 | Panel 1 | Panel 2 | Panel 3 | Panel 4 | Panel 5 |
| Mean (nmol/L) | 479.8 | 1156.3 | 1304.4 | 1980.6 | 3153.3 |
| n | 58 | 60 | 60 | 60 | 60 |
| SD (nmol/L) | 45.00 | 70.60 | 113.21 | 91.78 | 165.47 |
| CV (%) | 9.4 | 6.1 | 8.7 | 4.6 | 5.2 |
| min (nmol/L) | 388 | 871 | 891 | 1671 | 2561 |
| max (nmol/L) | 558 | 1255 | 1491 | 2136 | 3386 |
| median (nmol/L) | 485.5 | 1167 | 1337 | 1999 | 3192 |
| All | Panel 1 | Panel 2 | Panel 3 | Panel 4 | Panel 5 |
| Mean (nmol/L) | 520.2 | 1182.1 | 1343.4 | 1996.2 | 3214.8 |
| n | 177 | 180 | 179 | 178 | 180 |
| SD (nmol/L) | 52.94 | 82.19 | 97.37 | 96.39 | 165.44 |
| 95% CI (nmol/L) | 47.94-59.11 | 74.48-91.68 | 88.22-108.66 | 87.31-107.59 | 149.93-184.55 |
| CV (%) | 10.2 | 7.0 | 7.2 | 4.8 | 5.1 |
| min (nmol/L) | 388 | 871 | 891 | 1641 | 2561 |
| max (nmol/L) | 660 | 1346 | 1555 | 2179 | 3636 |
| median (nmol/L) | 491 | 1165 | 1330 | 2006 | 3179 |
Vantera® Clinical Analyzer for use with NMR LipoProfile® test Premarket Notification 510(k) Section 6 – 510(k) Summary
·
.
{14}------------------------------------------------
| HDL-C (mg/dL) | TG (mg/dL) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Pool # | 1 | 8 | 4 | 10 | 11 | Pool # | 2 | 4 | 3 | 6 | 9 |
| NMR 8001 | Panel 1 | Panel 2 | Panel 3 | Panel 4 | Panel 5 | NMR 8001 | Panel 1 | Panel 2 | Panel 3 | Panel 4 | Panel 5 |
| Mean (mg/dL) | 21.5 | 33.4 | 53.7 | 80.1 | 92.1 | Mean (mg/dL) | 66.1 | 70.3 | 133.5 | 153.5 | 343.3 |
| n | 60 | 60 | 60 | 60 | 60 | n | 60 | 60 | 59 | 60 | 60 |
| SD (mg/dL) | 0.75 | 1.39 | 1.81 | 3.70 | 2.61 | SD (mg/dL) | 1.84 | 2.15 | 4.35 | 5.92 | 7.09 |
| CV (%) | 3.5 | 4.2 | 3.4 | 4.6 | 2.8 | CV (%) | 2.8 | 3.1 | 3.3 | 3.9 | 2.1 |
| min (mg/dL) | 20 | 30 | 49 | 74 | 87 | min (mg/dL) | 61 | 64 | 120 | 129 | 321 |
| max (mg/dL) | 23 | 36 | 57 | 88 | 97 | max (mg/dL) | 69 | 73 | 141 | 163 | 356 |
| median (mg/dL) | 21.5 | 34 | 54 | 78.5 | 92 | median (mg/dL) | 66 | 71 | 134 | 155 | 345 |
| NMR 8002 | Panel 1 | Panel 2 | Panel 3 | Panel 4 | Panel 5 | NMR 8002 | Panel 1 | Panel 2 | Panel 3 | Panel 4 | Panel 5 |
| Mean (mg/dL) | 19.4 | 29.2 | 52.3 | 72.9 | 87.5 | Mean (mg/dL) | 70.3 | 74.6 | 141.4 | 169.7 | 361.1 |
| n | 59 | 60 | 60 | 60 | 60 | n | 59 | 60 | 59 | 60 | 60 |
| SD (mg/dL) | 0.68 | 1.13 | 1.34 | 1.49 | 1.28 | SD (mg/dL) | 1.30 | 1.59 | 3.03 | 3.10 | 5.01 |
| CV (%) | 3.5 | 3.9 | 2.6 | 2.0 | 1.5 | CV (%) | 1.8 | 2.1 | 2.1 | 1.8 | 1.4 |
| min (mg/dL) | 17 | 27 | 48 | 70 | 85 | min (mg/dL) | 68 | 72 | 131 | 160 | 341 |
| max (mg/dL) | 21 | 31 | 56 | 76 | 90 | max (mg/dL) | 74 | 82 | 149 | 176 | 372 |
| median (mg/dL) | 19 | 29 | 52 | 73 | 88 | median (mg/dL) | 70 | 74 | 142 | 170 | 361 |
| NMR 8003 | Panel 1 | Panel 2 | Panel 3 | Panel 4 | Panel 5 | NMR 8003 | Panel 1 | Panel 2 | Panel 3 | Panel 4 | Panel 5 |
| Mean (mg/dL) | 19.4 | 28.3 | 49.9 | 74.4 | 84.9 | Mean (mg/dL) | 66.5 | 70.4 | 134.3 | 160.9 | 339.8 |
| n | 58 | 60 | 60 | 60 | 60 | n | 60 | 60 | 60 | 60 | 60 |
| SD (mg/dL) | 0.90 | 1.41 | 2.36 | 4.26 | 3.39 | SD (mg/dL) | 2.70 | 3.44 | 4.77 | 7.10 | 18.50 |
| CV (%) | 4.6 | 5.0 | 4.7 | 5.7 | 4.0 | CV (%) | 4.1 | 4.9 | 3.5 | 4.4 | 5.4 |
| min (mg/dL) | 17 | 24 | 41 | 66 | 72 | min (mg/dL) | 57 | 58 | 119 | 123 | 267 |
| max (mg/dL) | 21 | 31 | 53 | 83 | 89 | max (mg/dL) | 71 | 74 | 145 | 169 | 357 |
| median (mg/dL) | 19 | 28 | 50 | 73 | 86 | median (mg/dL) | 67 | 72 | 135 | 162 | 346 |
| All | Panel 1 | Panel 2 | Panel 3 | Panel 4 | Panel 5 | All | Panel 1 | Panel 2 | Panel 3 | Panel 4 | Panel 5 |
| Mean (mg/dL) | 20.1 | 30.3 | 52.0 | 75.8 | 88.2 | Mean (mg/dL) | 67.6 | 71.8 | 136.4 | 161.4 | 348.0 |
| n | 177 | 180 | 180 | 180 | 180 | n | 179 | 180 | 178 | 180 | 180 |
| SD (mg/dL) | 1.26 | 2.60 | 2.45 | 4.56 | 3.91 | SD (mg/dL) | 2.76 | 3.21 | 5.41 | 8.66 | 14.99 |
| 95% CI (mg/dL) | 1.14-1.41 | 2.35-2.90 | 2.22-2.73 | 4.14-5.09 | 3.55-4.36 | 95% CI (mg/dL) | 2.50-3.08 | 2.91-3.59 | 4.90-6.03 | 7.75-9.66 | 13.59-16.72 |
| CV (%) | 6.3 | 8.6 | 4.7 | 6.0 | 4.4 | CV (%) | 4.1 | 4.5 | 4.0 | 5.4 | 4.3 |
| min (mg/dL) | 17 | 24 | 41 | 66 | 72 | min (mg/dL) | 57 | 58 | 119 | 123 | 267 |
| max (mg/dL) | 23 | 36 | 57 | 88 | 97 | max (mg/dL) | 74 | 82 | 149 | 176 | 372 |
| median (mg/dL) | 19 | 28 | 50 | 73 | 86 | median (mg/dL) | 67 | 71 | 135 | 162 | 344 |
Vantera® Clinical Analyzer for use with NMR LipoProfile® test Premarket Notification 510(k) Section 6 – 510(k) Summary
{15}------------------------------------------------
Premarket Notification 510(k) Vantera® Clinical Analyzer for use with NMR LipoProfile® test Section 6 - 510(k) Summary
Linearity
Three serum pools were prepared from patient specimens with low, medium and high values of LDL-P, HDL-C and Triglycerides as determined by NMR LipoProfile test. Each were mixed and diluted in different proportions to produce eleven (for LDL-P) or Twelve (12) (TG and HDL-C) different samples with widely varying target concentrations. Mean values from analysis of four replicates of each pool were compared to the expected target values to determine the percent bias for each sample. The serum pools were analyzed according to EP6-A. Tables and regression plots of the linearity data for LDL-P, HDL-P and Triglycerides are given below:
{16}------------------------------------------------
| Level | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Targetvalue | 225.4 | 263.375 | 673.75 | 1039.25 | 1222 | 1473.28 | 1770.25 | 2291.41 | 2968.22 | 3645.03 | 4321.84 |
| ObservedMean | 248.8 | 243.8 | 682.0 | 1115.0 | 1285.8 | 1402.3 | 1829.8 | 2437.5 | 3032.3 | 3644.3 | 4442.8 |
| % Bias | 10.3 | -7.5 | 1.2 | 7.3 | 5.2 | -4.8 | 3.4 | 6.4 | 2.2 | 0.0 | 2.8 |
Image /page/16/Figure/2 description: The image shows the measuring range for LDL-P, which is a type of cholesterol. The measuring range is from 300 to 3500 nmol/L. The text is in bold font.
Image /page/16/Figure/3 description: The image is a linearity plot showing the relationship between LDL-P (nmol/L) and Target LDL-P (nmol/L). The plot includes a linear fit line, with the equation Y=1.0193x + 7.8226 and an R-squared value of 0.9949. The x-axis represents the Target LDL-P (nmol/L) ranging from 0 to 4000, while the y-axis represents the LDL-P (nmol/L) ranging from 0 to 5000.
Y=1.0193x + 7.8226, R2 = 0.9949
{17}------------------------------------------------
Vantera® Clinical Analyzer for use with NMR LipoProfile® test Premarket Notification 510(k) Section 6 - 510(k) Summary
| Level | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 |
|---|---|---|---|---|---|---|---|---|---|
| Target value | 6.13 | 21.44 | 28.19 | 35.56 | 42.94 | 50.31 | 72.75 | 110.25 | 147.75 |
| Observed Mean | 5.00 | 22.50 | 29.25 | 36.25 | 43.25 | 50.75 | 81.50 | 117.25 | 151.50 |
| % Bias | - | 5.0 | 3.8 | 1.9 | 0.7 | 0.9 | 12.0 | 6.3 | 2.5 |
| HDL-C Measuring Range: 7-140 mg/dL | ||||
|---|---|---|---|---|
| -- | ------------------------------------ | -- | -- | -- |
Image /page/17/Figure/3 description: The image is a linearity plot showing HDL-C (mg/dL) on the y-axis and Target HDL-C (mg/dL) on the x-axis. There are two trendlines on the plot, one representing a linear fit with the equation (-0.3459 +1.049x) and the other representing a polynomial fit with the equation (-0.4884 +0.954x +0.003017x² -1.7074E-005x³). The equation Y= 1.0486x - 0.3459 and R² = 0.9961 are also included in the image.
Y=1.0486x - 0.3459, R2 = 0.9961
{18}------------------------------------------------
| Level | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Target value | 3.8 | 5.1 | 9.2 | 29.0 | 82.5 | 134.6 | 178.1 | 221.5 | 308.4 | 531.0 | 802.6 | 1074.2 | 1345.7 |
| Observedaverage | 5.5 | 6.8 | 11.0 | 26.3 | 84.5 | 135.0 | 177.8 | 219.3 | 306.0 | 536.0 | 816.8 | 1079.0 | 1356.3 |
| % Bias | 43.1 | 31.7 | 19.2 | -9.5 | 2.4 | 0.3 | -0.2 | -1.0 | -0.8 | 0.9 | 1.8 | 0.5 | 0.8 |
Image /page/18/Figure/2 description: The image shows the text "Triglycerides Measuring Range: 5-1100 mg/dL". This text indicates the range of values that can be measured for triglycerides, which are a type of fat in the blood. The measuring range is from 5 to 1100 milligrams per deciliter (mg/dL).
Image /page/18/Figure/3 description: The image is a linearity plot showing the relationship between target TG and TG. The x-axis represents the target TG in mg/dL, ranging from 0 to 1400, while the y-axis represents TG in mg/dL, also ranging from 0 to 1400. The plot includes a linear fit with the equation y = -0.3979 + 1.008x and a polynomial fit with the equation y = 0.7793 + 0.9864x + 4.9793E-005x^2 - 2.6257E-008x^3.
= 0.9999 Y=1.008x-0.3979, F
Reportable Range
The following are the reportable ranges for LDL-P, HDL-C and Triglycerides:
| LDL-P | 300 - 3500 nmol/L |
|---|---|
| HDL-C | 7 - 140 mg/dL |
| Triglycerides | 5-1100 mg/dL |
LipoScience, Inc.
{19}------------------------------------------------
Traceability, Stability, Assigned values (controls, calibrators)
The NMR Reference Standard
The NMR Reference Standard, TMA (Trimethylacetic acid, Sodium salt), is used as the NMR calibrator for the Vantera Clinical Analyzer. TMA is used routinely as a calibrator once daily during instrument startup to establish daily normalization factors. It also serves as a quality assessment tool to ensure quality NMR spectra are produced by the NMR analyzer.
The stability of the TMA calibrator material and storage conditions was evaluated for a period of 18 months across multiple NMR Analyzers. It was stored at room temperature and refrigerated at 4°C, in glass bottles and plastic bottles. TMA samples were evaluated for TMA signal methyl integrals every other month. The quality of the TMA spectra was not affected by the storage conditions during the study. The NMR Reference Standard is stable for 18 months in either glass or plastic bottle regardless of room temperature or refrigerated storage.
Liquichek™ Lipids Control
Liquichek™ Lipids Control material for LDL-P is frozen human serum in two pools, Level 1 and Level 2, prepared and packaged by Bio-Rad Laboratories. To assign values, new lots of Liquicheck™ Lipids Control material are run on 3 qualified Vantera Clinical Analyzers in house for 3 days. Means. Standard Deviations and % CVs are computed and new values are assigned.
The Liquicheck™ Lipids Control material is stable up to 6 months. Change in recovery over this period was estimated to be less than 0-6% for LDL-P.
{20}------------------------------------------------
Interfering Substances
|
Endogenous substances normally found in blood and exogenous substances (common and prescription drugs) were evaluated for potential interference with the NMR LipoProfile® test by LipoScience. Seven endogenous agents and twenty three drugs were screened for potential interfering effects to NMR LipoProfile test using concentrations in accordance to CLSI EP7-A2 guidelines.
| Endogenous | Exogenous (OTC drugs, etc.) | ||
|---|---|---|---|
| PotentialInterferent | TestConcentration | Potential Interferent | TestConcentration |
| Hemoglobin | 0.5 g/dL | Acetaminophen | 1324 µmol/L |
| Bilirubin,unconj. | 342 µmol/L20 mg/dL | Acetylsalicylic acid | 3.62 mmol/L |
| Creatinine | 442 µmol/L5 mg/dL | Atorvastatin | 600 µg Eq/L |
| Urea | 42.9 mmol/L | Clopidogrelhydrogensulfate** | 95.7 µmol/L |
| 260 mg/dL | Enalaprilat Dihydrate | 0.86 µmol/L | |
| Uric acid | 1.4 mmol/L23.5 mg/dL | Fenofibrate | 125 µmol/L |
| Protein(albumin) | 6 g/dL | Furosemide | 181 µmol/L |
| 60g/L | Glipizide | 4.48 µmol/L | |
| Bilirubin, conj | 342 µmol/L28.9 mg/dL | Hydralazinehydrochloride | 915.4 µmol/L |
| Heparin | 3000U/L | ||
| Ibuprofen Sodiumsalt | 2425 µmol/L | ||
| Isosorbide dinitrate | 636 nmol/L | ||
| Menhaden oil (FishOil) | 2.4 mg/mL | ||
| *Salicyclic acid at ≥ 1.3mmol/L was determined to interfere with LDL-P | |||
| **Clopidogrel hydrogensulfate at ≥ 95.7 µmol/L was determined to interfere withLDL-P | |||
| Potential Interferent | TestConcentration | ||
| MetforminHydrochloride | 3.62 mmol/L | ||
| Metoprolol tartrate | 18.7 µmol/L | ||
| Naproxen Sodium | 2170 µmol/L | ||
| Nicotinic AcidSodium salt | 8.28 mmol/L | ||
| Nifedipine | 1156 nmol/L | ||
| Pioglitazonehydrochloride | 152.7µmol/L | ||
| Piroxicam | 181 µmol/L | ||
| Pravastatin | 107.5 µmol/L | ||
| Salicylic Acid* | 1.3 mmol/L | ||
| Simvastatin | 114.7 µmol/L |
・・。
{21}------------------------------------------------
Method Comparison - Non-Clinical: H.
Method Comparison – LDL-P
Method comparison was evaluated by using serum samples across the reportable range of the NMR LipoProfile test for LDL-P on the Vantera Clinical Analyzer. LDL-P concentrations ranged from 303.0 to 3505.0nmol/L.
Vantera vs. NMR Profiler LDL-P Linear Regression Plot (n=1483)
Image /page/21/Figure/5 description: This scatter plot compares Vantera LDL-P to NMR Profiler LDL-P, with values ranging from 0 to 4000 on both axes. The plot includes a line of identity and a linear fit line represented by the equation y = -36.60 + 1.03x. Additionally, the plot displays 95% confidence interval bands around the linear fit.
Y=1.03x - 36.60 r=0.978
{22}------------------------------------------------
Method Comparison – HDL-C
Method comparison was evaluated by using serum samples across the reportable range of the NMR LipoProfile test for HDL-C on the Vantera Clinical Analyzer. HDL-C concentrations ranged from 7.0 to 132 mg/dL.
Vantera vs. NMR Profiler HDL-C Linear Regression Plot (n=1518)
Image /page/22/Figure/4 description: This image is a scatter plot with a linear fit. The x-axis is labeled "NMR Profiler HDL-C", and the y-axis is labeled "Vantera HDL-C". The plot shows a strong positive correlation between the two variables. The equation of the linear fit is Y=1.04x-1.20, and the correlation coefficient is r=0.989.
. .
{23}------------------------------------------------
Method comparison Triglycerides
Method comparison was evaluated by using serum samples across the reportable range of the NMR LipoProfile test for Triglycerides on the Vantera Clinical Analyzer. Triglyceride concentrations ranged from 18.0 to 1095.0 mg/dL.
Image /page/23/Figure/3 description: The image shows the title of a plot. The title says "Vantera vs. NMR Profiler TG Linear Regression Plot (n=1520)". This indicates that the plot is a linear regression plot comparing Vantera and NMR Profiler for TG (triglycerides) with a sample size of 1520.
Image /page/23/Figure/4 description: The image is a scatter plot titled "Scatter Plot with Fit". The x-axis is labeled "NMR Profiler TG" and ranges from 0 to 1200. The y-axis is labeled "Vantera TG" and ranges from 0 to 1200. The plot shows a strong positive correlation between the two variables, with data points clustered tightly around a linear fit line represented by the equation (0.92 + 1.00x).
Y=1.00x + 0.92 r=0.998
{24}------------------------------------------------
Standard/Guidance Documents Referenced (if applicable): K.
Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices.
Class II Special Controls Guidance Document: Instrumentation for Clinical Multiplex Test Systems
EP5-A2: Evaluation of Precision Performance of Quantitative Measurement Methods; Approves Guideline - Second Edition
EP6-A: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline
EP7-A2: Interference Testing in Clinical Chemistry; Approved Guideline - Second Edition
EP9-A2: Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline - Second Edition
EP17-A: Protocols for Determination of Limits of Detection and Limits of Quantification; Approved Guideline
EP14-A2: Evaluation of Matrix Effects: Approved Guideline - Second Edition
C28-A3: Defining, Establishing, and Verifying Reference Intervals in the Clinical
C53-A: Characterization and Oualification of Commutable Reference Materials for Laboratory Medicine; Approved Guideline
IEC 61010-1:2001-2nd Edition: Safety requirements for electrical equipment for measurement, control and laboratory use Part: General requirements
This device has not been tested by the Cholesterol Reference Method Laboratory Network.
M. Clinical Studies:
-
Clinical Sensitivity: a.
Not Applicable -
Clinical specificity: b.
Not Applicable
{25}------------------------------------------------
- Other clinical supportive data (when a. and b. are not applicable): c.
: .
Not Applicable
-
l. Clinical cut-off:
Not Applicable -
- Expected values/Reference range:
In order to determine the distribution of LDL-P levels expected in a representative sampling of the general population, serum samples (n=452) were analyzed from apparently healthy men (n=158) and women (n=294) (ranging from 18 to 84 years). The following table provides the concentrations of LDL-P by percentile in this reference population:
- Expected values/Reference range:
| All(n=452) | Men(n=158) | Women(n=294) | All(n=452) | Men(n=158) | Women(n=294) | |
|---|---|---|---|---|---|---|
| Percentile | LDL-P(nmol/L) | LDL-P(nmol/L) | LDL-P(nmol/L) | LDL-C(mg/dL) | LDL-C(mg/dL) | LDL-C(mg/dL) |
| 5 | 539 | 528 | 542 | 63 | 62 | 65 |
| 10 | 643 | 713 | 638 | 75 | 76 | 75 |
| 20 | 784 | 883 | 749 | 84 | 90 | 83 |
| 30 | 909 | 1004 | 863 | 94 | 100 | 91 |
| 40 | 1009 | 1087 | 970 | 102 | 107 | 98 |
| 50 | 1127 | 1241 | 1070 | 109 | 113 | 109 |
| 60 | 1248 | 1366 | 1202 | 118 | 128 | 115 |
| 70 | 1396 | 1505 | 1322 | 129 | 137 | 124 |
| 80 | 1572 | 1676 | 1482 | 140 | 147 | 136 |
| 90 | 1894 | 1941 | 1818 | 157 | 161 | 151 |
| 95 | 2047 | 2169 | 1986 | 169 | 171 | 169 |
Distribution of LDL-P Observed in a Reference Population
Based on the recommendations from a National Lipids Association expert panel, suggested reference values are provided in Table 2. The recommendation by the NLA has not been validated by a clinical study. Each laboratory should verify the validity of these reference values for the population it serves.
| LDL-P, nmol/L | |||
|---|---|---|---|
| Classification | |||
| Low / Normal | Intermediate | High | |
| Moderate | Borderline High | ||
| < 1000 | 1000-1299 | 1300-1599 | ≥ 1600 |
Recommended LDL-P Reference Values
{26}------------------------------------------------
HDL Cholesterol and Triglycerides
The following reference values for patient classification have been recommended by the NCEP and Adult Treatment Panel III Guidelines for HDL cholesterol and triglycerides for the assessment and management of CVD risk. Each laboratory should verify the validity of these reference values for the population it serves.
| HDL Cholesterol, mg/dL | Triglycerides, mg/dL | ||||
|---|---|---|---|---|---|
| Classification | Classification | ||||
| Low | High | Normal | BorderlineHigh | High | Very High |
| < 40 | $ \u2265 60 $ | < 150 | 150-199 | 200-499 | $ \u2265 500 $ |
0. System Description:
1. Modes of Operation:
The Vantera Clinical Analyzer is a 400 MHz proton nuclear magnetic resonance spectrometer.
-
- Software:
The FDA has reviewed the applicant's Hazard Analysis and software development process for this line of product type:
- Software:
Yes No
-
- Specimen Identification:
Bar code of source tube
- Specimen Identification:
-
- Specimen Sampling and Handling:
The processing of specimens on the Vantera Clinical Analyzer starts with their placement on the system. The user places serum or plasma specimen tubes in racks, and then places the racks on the system. After reading the bar code on a specimen tube, the system schedules the test or tests to be performed. The specimen is then aliquoted by the Metering Arm and is transferred to a dilution cup. Samples are prepared by diluting 2-fold (1:1) with specimen Diluent 1 performed by the Metering Arm assembly.
- Specimen Sampling and Handling:
{27}------------------------------------------------
-
- Calibration:
The instrument is calibrated with an aqueous solution of Trimethyl Acetate (TMA) as a disodium salt (15.0 mM) containing Na2EDTA (5.0 mM), CaCl2 (3.0 mM), KCI (120mM), D2O 10% v/v.
- Calibration:
-
- Quality Control:
It is recommended that two levels of quality control materials are tested in the same manner as patient samples, before or during patient sample processing for each analyte being tested. To verify system performance, analyze control materials:
- Quality Control:
-
After calibration .
-
According to federal, state or local regulations or at least once every day when patient testing is being performed.
Refer to the Liquichek™ Lipids Controls LDL-P value assignment card for LDL-P Target Ranges. It is recommended that each laboratory establish its own mean and acceptance range for each new lot of controls. Patient results should not be reported if the Quality Control values are not within the expected range.
Real-time quality control data indicate that stability for BioRad Liquichek Lipids controls is at least 6 months. A stability study is currently ongoing to extend the dating for the Bio-Rad Liquichek Lipids Controls.
P. Other Supportive Instrument Performance Characteristics Data Not Covered In the "Performance Characteristics" Section above:
Not Applicable
Proposed Labeling: Q.
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.
R. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/28/Picture/1 description: The image shows the seal of the Department of Health & Human Services (HHS) of the United States. The seal features the department's name arranged in a circular pattern around a stylized emblem. The emblem consists of a caduceus-like symbol, with a staff entwined by a serpent, representing health and medicine.
10903 New Hampshire Avenue Silver Spring, MD 20993
LipoScience, Inc. c/o Suzette Warner 2500 Sumner Boulevard Raleigh, NC 27616
AUG 3.0 2012
Re: K113830
Trade Name: Vantera® Clinical Analyzer; NMR LipoProfile® test on Vantera Clinical Analyzer Regulation Number: 21 CFR §862.2570 Regulation Name: Instrumentation for clinical multiplex test systems Regulatory Class: Class II Product Codes: NSU, MRR, LBS, CDT Dated: July 27, 2012 Received: July 30, 2012
Dear Ms. Warner:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
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If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at (301) 796-5760. For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/Medical
Devices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance ...
You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-5680 or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm
Sincerely yours,
N
Counney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indication for Use
510(k) Number (if known):
KII 3830
Device Name:
Vantera® Clinical Analyzer
Indications for Use:
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.
Prescription Use X (21 CFR Part 801 Subpart D) And/Or
Over the Counter Use (21 CFR Part 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OVD)
Ruta Clm
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K113830
Page 1 of 2
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Indication for Use
k 113830
510(k) Number (if known):
Device Name:
NMR LipoProfile® test on Vantera® Clinical Analyzer
Indications for Use:
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 NMRplasma asing nacroal maginal can and triglycerides are used in conjunction with other livid measurements and clinical evaluation to aid in the management of lipoprotein disorders associated with cardiovascular disease.
Prescription Use X : (21 CFR Part 801 Subpart D) And/Or .
Over the Counter Use (21 CFR Part 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)
Rute Chole
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K113830
§ 862.1705 Triglyceride test system.
(a)
Identification. A triglyceride test system is a device intended to measure triglyceride (neutral fat) in serum and plasma. Measurements obtained by this device are used in the diagnosis and treatment of patients with diabetes mellitus, nephrosis, liver obstruction, other diseases involving lipid metabolism, or various endocrine disorders.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 862.9.