(147 days)
Not Found
Yes
The device description explicitly states the use of a "Partial Least Squares (PLS) regression model" which is a statistical modeling technique used in machine learning for analyzing data with many predictor variables. The process involves "training" the model against chemical measurements and using "latent variables" to derive analyte concentrations, which are core concepts in machine learning model development and application.
No
The device is an in vitro diagnostic test used for the quantitative determination of certain lipids and apolipoproteins, which aids in diagnosis and treatment monitoring, rather than providing direct therapy.
Yes
The "Intended Use / Indications for Use" section explicitly states that the device is an "in vitro diagnostic test" and that its measurements are "used in the diagnosis and treatment of disorders" related to cholesterol, lipid metabolism, atherosclerosis, and various diseases.
No
The device description explicitly states it involves the acquisition of a 400 MHz proton NMR spectrum of serum or plasma, which requires a physical NMR spectrometer (hardware). The software component processes this spectral data, but it is dependent on the hardware for data acquisition.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use/Indications for Use: The document explicitly states that the assay is an "in vitro diagnostic test" for the quantitative determination of various lipid components in human serum. It also details how these measurements are used in the "diagnosis and treatment" of various disorders. This directly aligns with the definition of an IVD, which is used to examine specimens derived from the human body to provide information for the diagnosis, prevention, or treatment of a disease or condition.
- Device Description: The description details how the device analyzes a biological specimen (human serum or plasma) using a specific technology (NMR spectroscopy) to derive quantitative results (analyte concentrations). This process is performed outside of the human body, which is characteristic of an in vitro test.
- Performance Studies: The document includes details about analytical performance studies (sensitivity, precision, linearity, interference, method comparison) which are standard requirements for demonstrating the performance of an IVD.
- Predicate Devices: The mention of predicate devices with K numbers indicates that this device is being compared to other legally marketed IVDs.
Therefore, based on the provided information, the Extended Lipid Panel Assay is clearly an In Vitro Diagnostic device.
No
The letter does not explicitly state that the FDA has reviewed and approved or cleared a PCCP for this specific device; PCCP is listed as "Not Found" in the relevant section.
Intended Use / Indications for Use
The Extended Lipid Panel Assay is an in vitro diagnostic test for quantitative determination of Total Cholesterol, High Density Lipoprotein Cholesterol, and Triglycerides in human serum and Apolipoprotein B in human serum. Values for Total Cholesterol, High Density Lipoprotein Cholesterol, Triglycerides and Apolipoprotein B are calculated by the Vantera® Clinical Analyzer.
· Total Cholesterol measurements are used in the diagnosis and treatment of disorders involving excess cholesterol in the blood, lipid and lipoprotein metabolism disorders.
· High Density Lipoprotein Cholesterol measurements are used in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis, and various liver and renal diseases.
· Triglyceride measurements are used in the diagnosis and treatment of patients with diabetes mellitus, nephrosis, liver obstruction, other diseases involving lipid metabolism, or various endocrine disorders.
· Apolipoprotein B measurements are used in the diagnosis and treatment of lipid disorders and atherosclerosis.
Product codes (comma separated list FDA assigned to the subject device)
CHH, CDT, LBS, MSJ
Device Description
The Extended Lipid Panel Assay involves the acquisition of a 400 MHz proton NMR spectrum of serum or plasma, passing the spectral information through a Partial Least Squares (PLS) regression model, and deriving analyte concentrations from the spectrum based on the trained PLS model. The proton NMR spectrum of serum and plasma is replete with information from the lipids packaged in lipoproteins. The spectrum consists of multiple proton signals emanating from the TG, cholesteryl esters and free cholesterol present in chylomicrons, VLDL, LDL and HDL, out of which the methylene and methyl proton signals are the most abundant. NMR spectra were recorded for several hundred to several thousand representative serum specimens for which the TG, TC, HDL-C and ApoB were chemically measured. Using a PLS regression routine, the spectral information in the combined methylene and methyl region (0.56 - 1.40 ppm) was trained against the chemical measurements where the information is connected through latent variables. Cross-validation was performed with PRESS statistics to optimize the regression model with an appropriate number of latent variables. Once trained with sufficient number of specimens, for any test specimen spectrum, the spectral information is then converted into lipid or ApoB concentrations through the optimum number of 24 to 27 latent variables for which the regression coefficients were known from the predictor matrix.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
400 MHz proton NMR spectrum of serum or plasma
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Professional Use
Description of the training set, sample size, data source, and annotation protocol
NMR spectra were recorded for several hundred to several thousand representative serum specimens for which the TG, TC, HDL-C and ApoB were chemically measured. Using a PLS regression routine, the spectral information in the combined methylene and methyl region (0.56 - 1.40 ppm) was trained against the chemical measurements where the information is connected through latent variables.
Description of the test set, sample size, data source, and annotation protocol
Cross-validation was performed with PRESS statistics to optimize the regression model with an appropriate number of latent variables.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Analytical Sensitivity: The analytical sensitivity of the Extended Lipid Panel Assay was determined as the lowest concentration measurable with acceptable precision and accuracy. Limits of quantification (LoQ) are 24 mg/dL for TC, 15 mg/dL for TG, 13 mg/dL for HDL-C, and 18 mg/dL for ApoB.
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 40 total different runs over 20 days on 1 instrument. The pools were analyzed according to EP-5A.
Reproducibility: A reproducibility study was conducted in accordance to EP5-A2 at 3 sites each having 1 instrument 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.
Linearity: Reference serum pools were prepared from patient specimens with low to high values of TC, TG, HDL-C and ApoB as determined by the Extended Lipid Panel Assay. Each were mixed and diluted in different proportions to produce a range of 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.
TC Measuring Range: 66-868 mg/dL (R2= 1.000)
TG Measuring Range: 35-950 mg/dL (R^2= 1.000)
HDL-C Measuring Range: 14-152 mg/dL (R²= 1.000)
ApoB Measuring Range: 35-366 mg/dL (R-squared value of 0.999)
Interfering Substances: Endogenous substances normally found in blood and exogenous substances (common and prescription drugs) were evaluated for potential interference with the Extended Lipid Panel Assay test results. Eight endogenous agents and thirty drugs were screened for potential interfering effects to Extended Lipid Panel Assay test using samples with spiked concentrations of interferent in accordance to CLSI EP7-A2 guidelines.
Method Comparison - Non-Clinical: Method comparison was evaluated by using pooled serum samples across the reportable range of the Extended Lipid Panel Assay test for TC, TG, HDL-C and ApoB on the Vantera Clinical Analyzer. TC concentrations ranged from 71-859 mg/dL (n=281, r=0.994), TG concentrations ranged from 36 to 939.0 mg/dL (n=270), HDL-C concentrations ranged from 15 to 151.0 mg/dL (n=15575, r=0.985) and ApoB concentrations ranged from 36 to 344.0 mg/dL (n=266, r=0.980).
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Analytical sensitivity (LoQ):
TC: 24 mg/dL
TG: 15 mg/dL
HDL-C: 13 mg/dL
ApoB: 18 mg/dL
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
K012286, K031824, K873049, K063608
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 862.1175 Cholesterol (total) test system.
(a)
Identification. A cholesterol (total) test system is a device intended to measure cholesterol in plasma and serum. Cholesterol measurements are used in the diagnosis and treatment of disorders involving excess cholesterol in the blood and lipid and lipoprotein metabolism 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.
0
Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA logo on the right. The FDA logo features the letters 'FDA' in a blue square, followed by the words 'U.S. FOOD & DRUG ADMINISTRATION' in blue text.
October 18, 2018
Laboratory Corporation of America Holdings Suzette Warner Director, Quality Assurance and Regulatory Affairs 500 Perimeter Park Drive Morrisville, NC 27560
Re: K181373
Trade/Device Name: Extended Lipid Panel Assay Regulation Number: 21 CFR 862.1175 Regulation Name: Cholesterol (total) test system Regulatory Class: Class I, meets the limitation to the exemption 21 CFR 862.9 (c)(4) Product Code: CHH, CDT, LBS, MSJ Dated: September 12, 2018 Received: September 13, 2018
Dear Suzette 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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind vou, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. 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 Part
1
801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and
Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Kellie B. K
for Courtnev H. Lias. Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K181373
Device Name Extended Lipid Panel Assay
Indications for Use (Describe)
The Extended Lipid Panel Assay is an in vitro diagnostic test for quantitative determination of Total Cholesterol, High Density Lipoprotein Cholesterol, and Triglycerides in human serum and Apolipoprotein B in human serum. Values for Total Cholesterol, High Density Lipoprotein Cholesterol, Triglycerides and Apolipoprotein B are calculated by the Vantera® Clinical Analyzer.
· Total Cholesterol measurements are used in the diagnosis and treatment of disorders involving excess cholesterol in the blood, lipid and lipoprotein metabolism disorders.
· High Density Lipoprotein Cholesterol measurements are used in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis, and various liver and renal diseases.
· Triglyceride measurements are used in the diagnosis and treatment of patients with diabetes mellitus, nephrosis, liver obstruction, other diseases involving lipid metabolism, or various endocrine disorders.
· Apolipoprotein B measurements are used in the diagnosis and treatment of lipid disorders and atherosclerosis.
| Type of Use (Select one or both, as applicable) |
|---|
| ------------------------------------------------- |
| X Prescription Use (Part 21 CFR 801 Subpart D) | Over-The-Counter Use (21 CFR 801 Subpart C) |
|---|---|
| ------------------------------------------------------------------------------------------------ | --------------------------------------------- |
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3
510(k) Summary per 21CFR §807.92
1) 510(k) Number:
2) Submitted By
Laboratory Corporation of America Holdings 500 Perimeter Park Drive Morrisville, NC 27560 VTAC@labcorp.com
Contact Person: Suzette Warner Director, Quality Assurance and Regulatory Affairs LabCorp Ph: (919) 388-5539 warnes1@labcorp.com
3) Date Summary was Prepared:
October 1, 2018
4) Device Name(s)
Trade Name: Extended Lipid Panel Assay Common Name: Cholesterol Classification Names:
Triglyceride test system, 21 CFR 862.1705, Product Code CDT Cholesterol test system 21 CFR 862.1175, Product Code CHH Lipoprotein test system, 21 CFR 862.1475, Product Code LBS Lipoprotein test system, 21 CFR 862.1475, Product Code MSJ
Panel: Clinical Chemistry (75)
5) Legally Marketed Device to which Equivalence is Claimed (Predicate Device)
Roche Diagnostics HDL-Cholesterol plus 2nd Generation - K012286 Roche Diagnostics COBAS Integra Cholesterol Gen.2 - K031824 Roche Diagnostics Triglycerides GPO Without Free Glycerol - K873049 Dimension Vista Apolipoprotein B Flex reagent cartridge - K063608
4
6) Device Description
The Extended Lipid Panel Assay involves the acquisition of a 400 MHz proton NMR spectrum of serum or plasma, passing the spectral information through a Partial Least Squares (PLS) regression model, and deriving analyte concentrations from the spectrum based on the trained PLS model. The proton NMR spectrum of serum and plasma is replete with information from the lipids packaged in lipoproteins. The spectrum consists of multiple proton signals emanating from the TG, cholesteryl esters and free cholesterol present in chylomicrons, VLDL, LDL and HDL, out of which the methylene and methyl proton signals are the most abundant. NMR spectra were recorded for several hundred to several thousand representative serum specimens for which the TG, TC, HDL-C and ApoB were chemically measured. Using a PLS regression routine, the spectral information in the combined methylene and methyl region (0.56 - 1.40 ppm) was trained against the chemical measurements where the information is connected through latent variables. Cross-validation was performed with PRESS statistics to optimize the regression model with an appropriate number of latent variables. Once trained with sufficient number of specimens, for any test specimen spectrum, the spectral information is then converted into lipid or ApoB concentrations through the optimum number of 24 to 27 latent variables for which the regression coefficients were known from the predictor matrix.
7) Indications for Use
The Extended Lipid Panel Assay is an in vitro diagnostic test for quantitative determination of Total Cholesterol, High Density Lipoprotein Cholesterol, and Triglycerides in human serum and plasma, and Apolipoprotein B in human serum. Values for Total Cholesterol, High Density Lipoprotein Cholesterol, Triglycerides and Apolipoprotein B are calculated by the Vantera® Clinical Analyzer.
- Total Cholesterol measurements are used in the diagnosis and treatment of disorders involving excess cholesterol in the blood, lipid, and lipoprotein metabolism disorders.
- High Density Lipoprotein Cholesterol measurements are used in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis, and various liver and renal diseases.
- Triglyceride measurements are used in the diagnosis and treatment of patients with diabetes mellitus, nephrosis, liver obstruction, other diseases involving lipid metabolism, or various endocrine disorders.
- Apolipoprotein B measurements are used in the diagnosis and treatment of lipid disorders and atherosclerosis.
5
8) Comparison to the Predicate
The proposed device, Extended Lipid Panel Assay, is substantially equivalent to the predicates (K012286, K031824, K873049, K013206). The substantial equivalence is supported by its similarity in its intended use, sample type, patient population and testing environment. The key features are summarized in the following tables:
| | Total Cholesterol Assay
(Predicate) | Extended Lipid Panel Assay
(Proposed Device) |
|------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| 510(k) Number | K031824 | K181373 |
| Intended Use /
Indications for
Use | The cassette COBAS Integra
Cholesterol Gen.2 (CHOL2)
contains an in vitro diagnostic
reagent system intended use for
use on COBAS Integra systems
for the quantitative
determination of total
cholesterol in serum and
plasma. | The Extended Lipid Panel Assay
is an in vitro diagnostic test for
quantitative determination of Total
Cholesterol, in human serum and
plasma. Values are calculated by
the Vantera® Clinical Analyzer. |
| | Cholesterol measurements are
used in the diagnosis and
treatment of disorders involving
excess cholesterol in blood and
lipid and lipoprotein
metabolism disorders. | Total Cholesterol measurements
are used in the diagnosis and
treatment of disorders involving
excess cholesterol in the blood,
lipid, and lipoprotein metabolism
disorders. |
| Technology | Enzymatic colorimetric assay | Nuclear magnetic resonance |
| Sample Type | Human Serum and Plasma | Human Serum and Plasma |
| Population | General | General |
| Testing
Environment | Professional Use | Professional Use |
| Medical Decision
Limits | 240 mg/dL | 240 mg/dL |
| Sample size | 2μL | 150µL |
6
| | HDL Cholesterol
(Predicate) | Extended Lipid Panel Assay
(Proposed Device) |
|------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| 510(k) Number | K012286 | K181373 |
| Intended Use /
Indications for
Use | The cassette COBAS Integra
HDL-Cholesterol plus 2nd
Generation (HDL-C) contains an
in vitro diagnostic reagent
system intended for use on
COBAS Integra systems for the
quantitative determination of
HDL-cholesterol concentration
in serum and plasma.
A lipoprotein test system is a
device intended to measure
lipoprotein in serum and plasma.
Lipoprotein measurements are
used in the diagnosis and
treatment of lipid disorders (such
as diabetes mellitus),
atherosclerosis and various liver
and renal diseases. | The Extended Lipid Panel Assay
is an in vitro diagnostic test for
quantitative determination of High
Density Lipoprotein Cholesterol
(HDL-C), in human serum and
plasma. Values are calculated by
the Vantera® Clinical Analyzer.
High Density Lipoprotein
Cholesterol measurements are
used in the diagnosis and
treatment of lipid disorders (such
as diabetes mellitus),
atherosclerosis, and various liver
and renal diseases. |
| Technology | Enzymatic colorimetric assay | Nuclear magnetic resonance |
| Sample Type | Human Serum and Plasma | Human Serum and Plasma |
| Population | General | General |
| Testing
Environment | Professional Use | Professional Use |
| Medical Decision
Limits | 200 mg/dL | 200 mg/dL |
| Sample size | 2uL | 150μL |
8
| | Apo B
(Predicate) | Extended Lipid Panel Assay
(Proposed Device) |
|------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| 510(k) Number | K063608 | K181373 |
| Intended Use /
Indications for
Use | An in vitro diagnostic test for the
quantitative determination of
apolipoprotein B. | The Extended Lipid Panel Assay
is an in vitro diagnostic test for
quantitative determination of
ApoB in human serum. Values
are calculated by the Vantera®
Clinical Analyzer. |
| | Measurements of apolipoprotein
B aid in the diagnosis and
treatment of lipid disorders,
various liver and renal diseases,
and in the assessment of risk for
atherosclerosis and
cardiovascular disease. | Apolipoprotein B measurements
are used in the diagnosis and
treatment of lipid disorders and
atherosclerosis |
| Technology | Nephelometric immunoassay | Nuclear magnetic resonance |
| Sample Type | Human Serum and Plasma | Human Serum |
| Population | General | General |
| Testing
Environment | Professional Use | Professional Use |
| Medical Decision
Limits | 130 mg/dL | 130 mg/dL |
| Sample size | 19.6μL | 150μL |
9
9) Performance Data - Non-Clinical:
Analytical Sensitivity
The analytical sensitivity of the Extended Lipid Panel Assay was determined as the lowest concentration measurable with acceptable precision and accuracy. Limits of quantification (LoQ) are 24 mg/dL for TC, 15 mg/dL for TG, 13 mg/dL for HDL-C, and 18 mg/dL for ApoB.
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 40 total different runs over 20 days on 1 instrument. The pools were analyzed according to EP-5A. The results of this testing are summarized below:
Within-run Precision (n=20)
| Low Pool | Medium Pool | High Pool | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Mean | SD | %CV | Mean | SD | %CV | Mean | SD | %CV | |
| TC, mg/dL | 159.3 | 2.6 | 1.6 | 196.3 | 2.6 | 1.3 | 275.8 | 2.6 | 0.9 |
| TG, mg/dL | 128.4 | 1.0 | 1.0 | 157.7 | 1.6 | 1.0 | 317.4 | 3.1 | 1.0 |
| HDL-C, | |||||||||
| mg/dL | 36.6 | 0.9 | 2.4 | 49.9 | 0.8 | 1.6 | 91.2 | 1.2 | 1.3 |
| ApoB, mg/dL | 76.7 | 0.9 | 1.2 | 105.5 | 1.1 | 1.1 | 133.8 | 1.4 | 1.1 |
Within-Laboratory Precision (n=80)
| Low Pool | Medium Pool | High Pool | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Mean | SD | %CV | Mean | SD | %CV | Mean | SD | %CV | |
| TC, mg/dL | 166.6 | 2.7 | 1.6 | 197.1 | 2.8 | 1.4 | 279.6 | 3.2 | 1.1 |
| TG, mg/dL | 130.6 | 1.8 | 1.4 | 160.9 | 1.9 | 1.2 | 320.3 | 3.1 | 1.0 |
| HDL-C, mg/dL | 36.7 | 1.0 | 2.8 | 49.3 | 1.2 | 2.3 | 91.7 | 1.3 | 1.4 |
| ApoB, mg/dL | 78.9 | 1.9 | 2.4 | 109.4 | 2.4 | 2.2 | 137.9 | 2.6 | 1.9 |
Reproducibility
A reproducibility study was conducted in accordance to EP5-A2 at 3 sites each having 1 instrument 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.
10
| Low Pool | Medium Pool | High Pool | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Mean | SD | %CV | Mean | SD | %CV | Mean | SD | %CV | |
| TC, mg/dL | 142 | 5.2 | 3.6 | 214 | 4.8 | 2.1 | 316 | 6.6 | 2.1 |
| TG, mg/dL | 107 | 3.7 | 3.4 | 170 | 5.1 | 3.0 | 296 | 6.2 | 2.1 |
| HDL-C, | |||||||||
| mg/dL | 36 | 1.7 | 4.6 | 52 | 2.2 | 4.2 | 80 | 2.4 | 2.1 |
| ApoB, mg/dL | 85 | 5.7 | 6.7 | 115 | 4.9 | 4.2 | 164 | 6.2 | 3.7 |
Precision from Reproducibility Study
Linearity
Reference serum pools were prepared from patient specimens with low to high values of TC, TG, HDL-C and ApoB as determined by the Extended Lipid Panel Assay. Each were mixed and diluted in different proportions to produce a range of 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. Regression plots of the linearity data for TC, TG, HDL-C and ApoB are given below:
TC Measuring Range: 66-868 mg/dL
Image /page/10/Figure/7 description: The image is a plot titled "TC Linearity Plot". The x-axis is labeled "Expected TC (mg/dL)" and ranges from 0 to 900. The y-axis is labeled "Measured TC (mg/dL)" and ranges from 0 to 900. A red line is plotted on the graph, and the equation for the line is "Y= 1.010x -1.851, R2= 1.000".
11
TG Measuring Range: 35-950 mg/dL
Image /page/11/Figure/3 description: The image is a scatter plot titled "TG Linearity Plot". The x-axis is labeled "Expected TG (mg/dL)" and ranges from 0 to 1000. The y-axis is labeled "Measured TG (mg/dL)" and ranges from 0 to 1000. The plot shows a strong positive linear correlation between the expected and measured TG values, with the equation of the line being Y= 0.999x -1.086 and R^2= 1.000.
12
HDL-C Measuring Range: 14-152 mg/dL
Image /page/12/Figure/3 description: The image is a plot titled "HDL-C Linearity Plot". The x-axis is labeled "Expected HDL-C (mg/dL)" and ranges from 0 to 160. The y-axis is labeled "Measured HDL-C (mg/dL)" and ranges from 0 to 160. The plot shows a linear relationship between the expected and measured HDL-C values, with the equation of the line being Y= 1.063x -1.925, R²= 1.000.
13
Image /page/13/Figure/2 description: The image shows the measuring range for ApoB. The measuring range is from 35 to 366 mg/dL. The text is in bold font.
Image /page/13/Figure/3 description: The image is a scatter plot titled "ApoB Linearity Plot". The x-axis is labeled "Expected ApoB (mg/dL)" and ranges from 0 to 400. The y-axis is labeled "Measured ApoB (mg/dL)" and ranges from 0 to 400. The plot shows a linear relationship between the expected and measured ApoB values, with a regression equation of Y= 0.9853x -1.668 and an R-squared value of 0.999.
14
Interfering Substances
Endogenous substances normally found in blood and exogenous substances (common and prescription drugs) were evaluated for potential interference with the Extended Lipid Panel Assay test results. Eight endogenous agents and thirty drugs were screened for potential interfering effects to Extended Lipid Panel Assay test using samples with spiked concentrations of interferent in accordance to CLSI EP7-A2 guidelines.
| Endogenous | Potential
Interferent | Highest
Concentration
Tested (mg/dL) | Exogenous (OTC drugs, etc.) | Potential Interferent | Highest
Concentration
Tested (mg/dL) |
|------------|----------------------------|--------------------------------------------|-----------------------------|--------------------------|--------------------------------------------|
| | Bilirubin, unconj. | 20. | | Atorvastatin | 4.9 |
| | Bilirubin, conj. | 34 | | Fenofibrate | 4.5 |
| | Creatinine | 5.5 | | Acetylsalicylic acid | 66 |
| | Hemoglobin | 219 | | Acetaminophen | 20 |
| | Urea | 263 | | Naproxen | 28 |
| | Uric acid | 24 | | Ibuprofen | 44 |
| | Protein
(albumin) | 5986 | | Hydrochlorothiazide | 0.65 |
| | Triglycerides
(lipemic) | 633 | | Metoprolol | 1.5 |
| | | | | Nifedipine | 0.04 |
| | | | | Enalaprilat | 0.04 |
| | | | | Hydralazine | 19 |
| | | | | Metformin | 65 |
| | | | | Salicylic acid | 61 |
| | | | | Clopidogrel | 9.5 |
| | | | | Furosemide | 6.3 |
| | | | | Glipizide | 0.23 |
| | | | | Heparin | 303533 mU/dL |
| | | | | Isosorbide dinitrate | 0.02 |
| | | | | Menhaden Oil | 241 |
| | | | | Acetylcysteine | 125 |
| | | | | | |
| | Ampicillin | 6.1 | | Ascorbic Acid | 6.2 |
| | Calcium Dobesilate | 30 | | Cyclosporine | 6.1 |
| | Cefoxitin | 70 | | Levodopa
(L-DOPA) | 1.6 |
| | Methyldopa | 1.6 | | Metronidazole | 12 |
| | Doxycycline | 3.1 | | Rifampin
(Rifampicin) | 34 |
15
| Endogenous | Exogenous (OTC drugs, etc.) | |||||
|---|---|---|---|---|---|---|
| Potential | ||||||
| Interferent | Highest | |||||
| Concentration | ||||||
| Tested | ||||||
| (mg/dL) | Potential | |||||
| Interferent | Highest | |||||
| Concentration | ||||||
| Tested | ||||||
| (mg/dL) | Potential | |||||
| Interferent | Highest | |||||
| Concentration | ||||||
| Tested | ||||||
| (mg/dL) | ||||||
| Bilirubin, | ||||||
| unconj. | 20 | Atorvastatin | 4.9 | Hydralazine | 19 | |
| Bilirubin, conj. | 34 | Fenofibrate | 4.5 | Metformin | 65 | |
| Creatinine | 5.5 | Acetylsalicylic | ||||
| acid | 66 | Salicylic acid | 61 | |||
| Hemoglobin | 219 | Acetaminophen | 20 | Clopidogrel | 18 | |
| Urea | 263 | Naproxen | 42 | Furosemide | 6.3 | |
| Uric acid | 24 | Ibuprofen | 59 | Glipizide | 0.23 | |
| Protein | ||||||
| (albumin) | 5987 | Hydrochlorothiaz | ||||
| ide | 0.65 | Heparin | 303533 mU/dL | |||
| Triglycerides | ||||||
| (lipemic) | 500 | Metoprolol | 1.5 | Isosorbide | ||
| dinitrate | 0.02 | |||||
| Nifedipine | 0.04 | Menhaden Oil | 241 | |||
| Enalaprilat | 0.04 |
Substances tested in vitro that did not exhibit interference with TC test results.
Substances tested in vitro that did not exhibit interference with HDL-C test results.
| Endogenous | Exogenous (OTC drugs, etc.) | ||||
|---|---|---|---|---|---|
| Potential | |||||
| Interferent | Highest | ||||
| Concentration | |||||
| Tested | |||||
| (mg/dL) | Potential | ||||
| Interferent | Highest | ||||
| Concentration | |||||
| Tested | |||||
| (mg/dL) | Potential | ||||
| Interferent | Highest | ||||
| Concentration | |||||
| Tested | |||||
| (mg/dL) | |||||
| Bilirubin, | |||||
| unconj. | 20 | Atorvastatin | 4.9 | Hydralazine | 19 |
| Bilirubin, conj. | 34 | Fenofibrate | 4.6 | Metformin | 65 |
| Creatinine | 5.5 | Acetylsalicylic | |||
| acid | 66 | Salicylic acid | 61 | ||
| Hemoglobin | 219 | Acetaminophen | 20 | Clopidogrel | 18 |
| Urea | 263 | Naproxen | 28 | Furosemide | 6.3 |
| Uric acid | 24 | Ibuprofen | 44 | Glipizide | 0.23 |
| Protein | |||||
| (albumin) | 7493 | Hydrochlorothiaz | |||
| ide | 0.65 | Heparin | 303533 mU/dL | ||
| Triglycerides | |||||
| (lipemic) | 1135 | Metoprolol | 1.5 | Isosorbide | |
| dinitrate | 0.02 | ||||
| Nifedipine | 0.04 | Menhaden Oil | 242 | ||
| Enalaprilat | 0.04 |
16
| Endogenous | Exogenous (OTC drugs, etc.) | ||||
|---|---|---|---|---|---|
| Potential | |||||
| Interferent | Highest | ||||
| Concentration | |||||
| Tested | |||||
| (mg/dL) | Potential | ||||
| Interferent | Highest | ||||
| Concentration | |||||
| Tested (mg/dL) | Potential | ||||
| Interferent | Highest | ||||
| Concentration | |||||
| Tested (mg/dL) | |||||
| Bilirubin, | |||||
| unconj. | 20 | Atorvastatin | 4.9 | Hydralazine | 19 |
| Bilirubin, conj. | 34 | Fenofibrate | 4.5 | Metformin | 65 |
| Creatinine | 5.5 | Acetylsalicylic acid | 66 | Salicylic acid | 61 |
| Hemoglobin | 219 | Acetaminophen | 20 | Clopidogrel | 18 |
| Urea | 263 | Naproxen | 56 | Furosemide | 6.3 |
| Uric acid | 24 | Ibuprofen | 29 | Glipizide | 0.23 |
| Protein | |||||
| (albumin) | 5987 | Hydrochlorothiazide | 0.65 | Heparin | 303533 mU/dL |
| Metoprolol | 1.5 | Isosorbide | |||
| dinitrate | 0.02 | ||||
| Nifedipine | 0.04 | Menhaden Oil | 241 | ||
| Enalaprilat | 0.04 |
Substances tested in vitro that did not exhibit interference with TG test results.
H. Method Comparison - Non-Clinical:
Method comparison was evaluated by using pooled serum samples across the reportable range of the Extended Lipid Panel Assay test for TC, TG, HDL-C and ApoB on the Vantera Clinical Analyzer. TC concentrations ranged from 71-859 mg/dL, TG concentrations ranged from 36 to 939.0 mg/dL, HDL-C concentrations ranged from 15 to 151.0 mg/dL and ApoB concentrations ranged from 36 to 344.0 mg/dL.
17
Image /page/17/Figure/2 description: This image is a scatter plot comparing Vantera NMR TC to Predicate Device TC. The x-axis represents Predicate Device TC in mg/dL, ranging from 0 to 900, while the y-axis represents Vantera NMR TC, also ranging from 0 to 900. A Deming fit line is plotted with the equation y = 7.273 + 0.9737x, and the correlation coefficient r is 0.994. The plot also includes lines indicating the allowable difference of plus or minus 10 or 10% and a 95% confidence interval.
Vantera NMR (candidate device) vs. Predicate Device TC Regression Plot (n=281)
Vantera NMR (candidate device) vs. Predicate device TG Regression Plot (n=270)
Image /page/17/Figure/5 description: This image is a scatter plot comparing Vantera NMR TG values. The x and y axes both range from 0 to 1000. A Deming fit line is plotted with the equation y = -3.858 + 0.9805x, along with a 95% confidence interval and an allowable difference of ±10 or ±10%.
Predicate Device TG (mg/dL)
18
Image /page/18/Figure/2 description: This image is a scatter plot comparing Vantera NMR HDL-C and Predicate Device HDL-C, both measured in mg/dL. The plot includes a Deming fit line represented by the equation y = 0.789 + 1x, with a correlation coefficient (r) of 0.985. The plot also shows lines indicating the allowable difference of plus or minus 10 or 10%, as well as 95% confidence intervals.
Vantera NMR (candidate device) vs. Predicate Device HDL-C Regression Plot (n=15575)
Vantera NMR (candidate device) vs. Comparator Device ApoB Regression Plot (n=266)
Image /page/18/Figure/5 description: The image is a scatter plot comparing Vantera NMR ApoB and Comparator Device ApoB, both measured in mg/dL. The plot includes a Deming fit line, represented by the equation y = -1.007 + 0.9699x, and a 95% confidence interval. The equation Y = 0.9699x - 1.007 and the correlation coefficient r = 0.980 are displayed on the plot, indicating a strong positive correlation between the two measurement methods. Allowable difference lines of plus or minus 10 or 10% are also shown.
19
10) Conclusion:
The submitted information in this premarket notification provides the data necessary to demonstrate substantial equivalence based on analytical validations and predicate comparisons.
This 510(k) summary is being submitted in accordance with the requirements of the Safe Medical Device Act of 1991 and the implementing regulation 21 CFR 807.92.