(427 days)
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No
The device description and performance studies focus on a biochemical assay using enzymatic reactions and surfactants to measure sd LDL-C. There is no mention of AI or ML in the text.
No
The device is an in vitro diagnostic test for measuring sdLDL-cholesterol, used for risk management of lipoprotein disorders, not for direct treatment or therapy.
Yes
This device quantitatively determines sd LDL cholesterol in human serum or plasma to aid in the risk management of lipoprotein disorders associated with cardiovascular disease. This is a diagnostic function because it provides information for determining a disease state or condition.
No
The device description clearly outlines a chemical assay involving reagents and enzymatic reactions to measure sd LDL-C. This indicates a hardware-based laboratory test, not a software-only device.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states it is for the "quantitative determination of small, dense (sd) LDL cholesterol (-C) in human serum or plasma." This is a measurement performed on a biological sample taken from the human body.
- Device Description: The description details a laboratory assay involving chemical reactions with biological samples (serum or plasma) using reagents and enzymes to measure a specific analyte (sd LDL-C).
- Performance Studies: The document includes extensive performance studies conducted on biological samples (serum, plasma) to evaluate analytical performance (precision, linearity, interference, matrix equivalence) and clinical performance (reference range, association with clinical outcomes).
These characteristics are all consistent with the definition of an In Vitro Diagnostic device, which is used to examine specimens derived from the human body to provide information for diagnostic, monitoring, or screening purposes.
N/A
Intended Use / Indications for Use
The s LDL-EX"SEIKEN" test is for the quantitative determination of small, dense (sd) LDL cholesterol (-C) in human serum or plasma. The s LDL-EX"SEIKEN" test is used in conjunction with other lipid measurements and clinical evaluations to aid in the risk management of lipoprotein disorders associated with cardiovascular disease.
Product codes (comma separated list FDA assigned to the subject device)
PYP
Device Description
The assay consists of two steps and is based on the technique to use well-characterized surfactants and enzymes that selectively react with certain groups of lipoproteins.
In the first step, non-sd LDL lipoproteins, that is, chylomicrons, VLDL, IDL, L-LDL and HDL are decomposed by a surfactant and sphingomyelinase in Reagent-1 that is reactive to those non-sd LDL lipoproteins. The cholesterol released from such non-sd LDL lipoproteins is then degraded to water and oxygen by the action of enzymes. Cholesterol ester is hydrolyzed by the cholesterol esterase (CHE) and then oxidized by the cholesterol oxidase (CO). Produced hydrogen peroxides are finally decomposed to water and oxygen by the catalase.
In the second step, another surfactant in Reagent-2 releases cholesterol only from sd LDL particles and cholesterol released from sd LDL is then subject to the enzymatic reactions. As catalase in the reaction mixture is inhibited by sodium azide in Reagent-2, hydrogen peroxides, produced from the reaction with the cholesterol esterase and cholesterol oxidase, develop a purple-red color with the coupler in the presence of peroxidase (POD).
Mentions image processing
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Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
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Anatomical Site
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Indicated Patient Age Range
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Intended User / Care Setting
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Description of the training set, sample size, data source, and annotation protocol
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Description of the test set, sample size, data source, and annotation protocol
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Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Nonclinical Data:
- Limit of Blank, Detection, Quantitation: LoB was 0.20 mg/dL, LoD was 0.38 mg/dL, and LoQ was 1.14 mg/dL.
- Precision: Performed at three sites. Within-laboratory %CV (total precision) for various samples ranged from 1.3 % to 4.3%.
- Linearity: Study included 13 samples. The assay results were linear throughout the entire dynamic range (4.0 - 100 mg/dL).
- Spike and Recovery: % differences for each spiked serum sample ranged from -0.5 to +1.3%.
- Interferences: No significant interference up to tested levels for Hemoglobin, Bilirubin (conjugated and unconjugated), Chyle, Sodium L-ascorbate, Intralipid, Uric acid, Triglyceride, and various drugs (Pravastatin, Pitavastatin, Atorvastatin, Rosuvastatin, Simvastatin, Ezetimibe, Fenofibrate, Gamma-Oryzanol, Bezafibrate, Probucol, Tocophenol Nicotinate, and Riboflavin Tetrabutyrate).
- Matrix Equivalence- sample tubes: Correlation Coefficient of 1.00 for Serum (SST), Plasma (K2 EDTA), and Plasma (Lithium Heparin) compared to plain serum. Slopes ranged from 0.96 to 1.00 and Intercepts from -0.4 to +0.1.
Clinical Data:
- Reference Range Study: Specimens from four subgroups of volunteers (younger/older men, pre/post-menopausal women) presumptively free from CHD. Total sample size not explicitly stated but implied to be 442 (210 male + 232 female). Reference range was determined to be 12.7 to 48.3 mg/dL for younger subjects and 12.6 to 51.7 mg/dL for older subjects. SD LDL-C values differ by age (higher with increasing age), but not by gender.
- Clinical Studies (Validation of cutoff): Utilized banked samples and clinical outcome data from Visit 4 of the Atherosclerosis Risk in Communities (ARIC) study. Objective: investigate the relationship between sd LDL-C levels and incident CHD risk and validate a cutoff of 50.0 mg/dL.
- Absolute risk analyses: For sd LDL-C
§ 862.1475 Lipoprotein test system.
(a)
Identification. 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.(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.
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510(k) SUMMARY
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92. The assigned 510(k) number is K161679.
807.92 (a)(1)- Submitter Information
| Submitter | Name: | Denka Seiken Co., Ltd. |
|---|---|---|
| Address: | 1359-1 Kagamida, Kigoshi, Gosen-shi, | |
| Niigata, Japan | ||
| Phone: | 81+250-42-0721 FAX: 81+250-43-8813 | |
| Contact | Name: | Thomas M. Tsakeris |
| Devices & Diagnostics Consulting Group, Inc. | ||
| Address: | 16809 Briardale Road Rockville, MD 20855 | |
| Phone: | 301-330-2076 Email: DDCGI@Comcast.net |
The Date the Summary was Prepared: August 18, 2017
807.92 (a)(2) Device name- trade name and common name, and classification
Trade Names:
- · s LDL-EX "SEIKEN"
Common Names:
- · Low-density lipoprotein (LDL) cholesterol sub-fraction test
Classification Names:
REAGENTS Class: Class I, meets the limitation to the exemption 862.9(c)(4) Panel: 75, Clinical Chemistry Product Code: PYP
807.92 (a)(3): Identification of the legally marketed predicate devices
The predicate device is Liposcience's (Liposcience, Inc., Raleigh, NC) NMR Lipoprofile Assay (K111516, cleared September 27, 2011).
807.92 (a)(4): Device Description
The assay consists of two steps and is based on the technique to use well-characterized surfactants and enzymes that selectively react with certain groups of lipoproteins.
In the first step, non-sd LDL lipoproteins, that is, chylomicrons, VLDL, IDL, L-LDL and HDL are decomposed by a surfactant and sphingomyelinase in Reagent-1 that is reactive to those non-sd LDL lipoproteins. The cholesterol released from such non-sd LDL lipoproteins is then degraded to water and oxygen by the action of enzymes. Cholesterol ester is hydrolyzed by the
1
cholesterol esterase (CHE) and then oxidized by the cholesterol oxidase (CO). Produced hydrogen peroxides are finally decomposed to water and oxygen by the catalase.
In the second step, another surfactant in Reagent-2 releases cholesterol only from sd LDL particles and cholesterol released from sd LDL is then subject to the enzymatic reactions. As catalase in the reaction mixture is inhibited by sodium azide in Reagent-2, hydrogen peroxides, produced from the reaction with the cholesterol esterase and cholesterol oxidase, develop a purple-red color with the coupler in the presence of peroxidase (POD).
807.92 (a)(5): Intended Use
The s LDL-EX"SEIKEN" test is for the quantitative determination of small, dense (sd) LDL cholesterol (-C) in human serum or plasma. The s LDL-EX"SEIKEN" test is used in conjunction with other lipid measurements and clinical evaluations to aid in the risk management of lipoprotein disorders associated with cardiovascular disease.
807.92 (a)(6): Technological Similarities and Differences to the Predicate
COMPARATIVE CHART
| Parameter | s LDL-EX“SEIKEN”
K161679 | NMR LipoProfile
K111516 |
|--------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use/
Indications for Use | The s LDL-EX“SEIKEN” is for the
quantitative determination of small, dense
(sd) LDL cholesterol (-C) in human serum
or plasma.
The s LDL-EX“SEIKEN” test system is
used in conjunction with other lipid
measurements and clinical evaluations to
aid in the risk management of lipoprotein
disorders associated with cardiovascular
disease. | The NMR LipoProfile® test, when used
with the NMR Profiler, 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. This test is
performed and provided as a service by
LipoScience Laboratory. |
Similarities to Predicate
Differences from Predicate
| Methodology | Colorimetric Assay | NMR Spectrometer |
|---|---|---|
| ------------- | -------------------- | ------------------ |
807.92 (b)(1): Brief Description of Nonclinical Data
A series of studies were performed that evaluated traditional laboratory performance characteristics; a summary of each study follows. The Roche Diagnostics Hitachi 917 was used in the studies.
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Limit of Blank, Detection, Quantitation
The testing was based on guidance from the Clinical and Laboratory Standards Institute document CLSI Protocol EP17-A2; LoB and LoD were evaluated using the classical approach, and LoQ was evaluated as functional sensitivity, identifying the lowest concentration with %CVs less than 10%. The LoB was 0.20 mg/dL, the LoD was 0.38 mg/dL, and the LoQ was 1.14 mg/dL.
Precision
Precision testing was performed at a total of three sites (Denka plus two external sites) according to the Clinical and Laboratory Standards Institute (CLSI) EP05-A2 approved guideline. Samples were assayed twice a day, two replicates per run, for 20 days, for a total of 80 results per sample. From these results, within-laboratory (total precision) was analyzed.
The study included five samples, namely the 2-level control set, and three serum-based pools. The three serum based pools used in the sites where different, but were representative of low, intermediate, and high sd LDL-C concentrations. Each site employed one lot of assay reagents.
| Lipid Control I | Lipid Control II | Human Serum L | Human Serum M | Human Serum H | |
|---|---|---|---|---|---|
| n | 80 | 80 | 80 | 80 | 80 |
| Mean (mg/dL) | 17.03 | 56.89 | 7.80 | 43.85 | 74.55 |
| Within-laboratory SD (mg/dL) | 0.39 | 0.92 | 0.16 | 0.58 | 1.05 |
| Within-laboratory %CV | 2.3% | 1.6% | 2.1% | 1.3% | 1.4% |
Site 1
Site 2
| | Lipid Control
I | Lipid Control
II | Human
Serum L | Human
Serum M | Human
Serum H |
|------------------------------|--------------------|---------------------|------------------|------------------|------------------|
| n | 80 | 80 | 80 | 80 | 80 |
| Mean (mg/dL) | 20.98 | 54.05 | 7.90 | 44.53 | 75.85 |
| Within-laboratory SD (mg/dL) | 0.45 | 1.02 | 0.25 | 0.81 | 1.34 |
| Within-laboratory %CV | 2.1% | 1.9% | 3.2% | 1.8% | 1.8% |
Site 3
| Lipid Control I | Lipid Control II | Human Serum L | Human Serum M | Human Serum H | |
|---|---|---|---|---|---|
| n | 80 | 80 | 80 | 80 | 80 |
| Mean (mg/dL) | 18.05 | 55.39 | 7.78 | 44.96 | 75.82 |
| Within-laboratory SD (mg/dL) | 0.74 | 1.33 | 0.34 | 0.86 | 1.67 |
| Within-laboratory %CV | 4.1% | 2.4% | 4.3% | 1.9% | 2.2% |
The within-laboratory %CV (total precision) for each control or sample, at each site, ranged from 1.3 % to 4.3%.
Linearity
The linearity study was performed according to the Clinical and Laboratory Standards Institute (CLSI) EP06-A approved guideline. The study included 13 samples that were tested in duplicate
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with results averaged; the concentration span of the 13 samples was 0 to 127 mg/dL, and the study used one lot of reagents.
Absolute value of nonlinearity was less than allowable nonlinearity at all tested levels. The assay results obtained by s LDL-EX"SEIKEN" were shown to be linear throughout the entire dynamic range (4.0 - 100 mg/dL).
Spike and Recovery
High Concentration Control (sd LDL-C: 90 to100 mg/dL) was used as a spiking sample. The Control and three levels sd LDL-C serum samples were first assayed in triplicate with s LDL-EX"SEIKEN," and mean values were used to calculate theoretical values. After spiking each sample was assayed in triplicate with s LDL-EX"SEIKEN," and mean values were calculated. The mean values from s LDL-EX"SEIKEN" were then compared to the theoretical values.
| | High
Concentration
Control | Serum | | |
|--------------|----------------------------------|-------|--------|------|
| | | Low | Medium | High |
| n | 3 | 3 | 3 | 3 |
| Mean (mg/dL) | 94.5 | 25.0 | 40.5 | 64.5 |
Each sample (before spiking)
Spiked Sera
| Sample 1 | Sample 2 | Sample 3 | Sample 4 | Sample 5 | Sample 6 | |
|---|---|---|---|---|---|---|
| Combination | Low : Control | Medium : Control | High : Control | |||
| 1:1 | 3:1 | 1:1 | 3:1 | 1:1 | 3:1 | |
| Theoretical value (mg/dL) | 59.8 | 42.4 | 67.5 | 54.0 | 79.5 | 72.0 |
| n | 3 | 3 | 3 | 3 | 3 | 3 |
| Mean (mg/dL) | 59.6 | 42.2 | 68.0 | 54.4 | 80.2 | 72.9 |
| %Δ | -0.3% | -0.5% | +0.7% | +0.7% | +0.9% | +1.3% |
The % differences for each spiked serum sample ranged from -0.5 to +1.3%.
Interferences
Concentrations of the potential interferents and the testing protocol were based on guidance from the Clinical and Laboratory Standards Institute document CLSI Protocol EP07-A2. Three human serum samples that spanned the dynamic range were used for each compound. The samples were divided into two series of aliquots: one aliquot was spiked to represent the interfering sample, and another aliquot remained neat to represent the control sample. All samples were assayed in triplicate and results were averaged. Non-interference was defined as less than 10% difference or 3 mg/dL difference (for the low level) between neat and spiked samples. The results are summarized below:
- Hemoglobin: No significant interference up to 1,000 mg/dL
- Bilirubin: No sign No significant interference up to 60 mg/dL of both conjugated and unconjugated bilirubin.
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- Chyle: No significant interference up to 1,420 FTU
- Sodium L-ascorbate: No significant interference up to 100 mg/dL ●
- Intralipid (Intralipid 20%): No significant interference up to 10%. (up to 1% wt/vol as ● soybean oil)
- Uric acid: No significant interference up to 15 mg/dL
- Triglyceride: No significant interference up to 1.500 mg/dL
Drugs: No interference was found at three-times the therapeutic levels using Pravastatin, Pitavastatin, Atorvastatin, Rosuvastatin, Simvastatin, Ezetimibe, Fenofibrate, Gamma-Oryzanol, Bezafibrate, Probucol, Tocophenol Nicotinate, and Riboflavin Tetrabutyrate.
The differences, or percent differences, for all spiked compounds were within the allowable ranges.
Matrix Equivalence- sample tubes
Multiple serum and plasma samples were drawn from 48 subjects. The tube types were: serum (reference, "plain"), serum separator tubes (SST), K2 EDTA tubes, and lithium heparin tubes. Samples from each tube type were assaved in duplicate, but for the analyses, the x-axis was the mean of the duplicate testing of the plain tube, and the y-axis was the first result from the other four (4) tubes. The plain tube was considered the reference condition.
Calculated correlation coefficients, slopes, and intercepts, with the plain results on the x-axis., are shown in the tables below. Line listings follow.
| | Serum
(SST) | Plasma
(K2 EDTA) | Plasma
(Lithium
Heparin) |
|----------------------------|----------------|---------------------|--------------------------------|
| Correlation
Coefficient | 1.00 | 1.00 | 1.00 |
| Slope | 1.00 | 0.96 | 0.99 |
| Intercept | +0.1 | -0.1 | -0.4 |
807.92 (b)(2): Brief Description of Clinical Data
Reference Range Study
A reference range study was conducted as there are currently no reference intervals established for small dense (sd) low density lipoprotein (LDL) cholesterol (-C). Specimens from four subgroups of volunteers, who were presumptively free from coronary heart disease (CHD) and were representative of normal lipid panel results, were assayed by s LDL-EX"SEIKEN." Specimens were collected from both younger and older men (defined as less than or equal to, or greater than 44 years of age) and women of pre and post-menopausal status (defined as less than or equal to or greater than 54 years of age).
Eligible subjects were enrolled at two U.S. regions and consented to a single blood draw after an overnight fast; subjects also consented to completing health and demographic questionnaires, and the measurement of various vital signs; all subjects who entered the study at either center were
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treated in the same manner. Following the CLSI guideline, the normal range for sd LDL-C value was selected as the central 95% interval. removing the lower 2.5% and the upper 2.5%.
Further analysis was carried out to clarify the association between sd LDL-C concentrations and age and/or gender. Subjects were stratified into two groups divided by gender (Table 1a), and by age (Table 1b). Table 1a clearly shows that sd LDL-C levels do not differ by gender (p=0.7564); however, Table 1b shows sd LDL-C levels are significantly higher in the older groups when combining male and female subjects (p= 50mg/dL". The x-axis is labeled "Follow-up years" and ranges from 0 to 15. The y-axis represents survival probability and ranges from 0.75 to 1.00. There are two survival curves, one for sdLDL-C=50mg/dL, with the former showing higher survival rates.
Figure 1: Kaplan-Meier survival curves of incident CHD and sd LDL-C chiSq) for linear hypothesis testing results of sd LDL-C quartiles).
| sd LDL-C, Quartile | |||||
|---|---|---|---|---|---|
| 1 | |||||
| ( |