(42 days)
For the quantitative in vitro determination of HDL Cholesterol in serum and plasma. Such measurements are used in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis and renal diseases and for the assessment for the risk of developing cardiovascular disease.
This in vitro diagnostic device is intended for Rx Only.
The Direct HDL Cholesterol (HDL) kit assay consists of ready to use reagent solutions.
CATALOGUE NUMBER: CH8311
R1. Enzyme Reagent 1 4 x 20 ml
R2. Enzyme Reagent 2 4 x 9 ml
REAGENT COMPOSITION
R1. Enzyme Reagent 1 N,N-Bis(2-hydroxyethyl)- 2-aminoethanesulfonic acid N-(2-hydroxy-3-Sulfopropyl)- 3,5-dimethoxyaniline, sodium salt (HDAOS) Cholesterol Esterase [E.C.3.1.1.13. Microorganism] Cholesterol Oxidase [E.C.1.1.3.6. Streptomyces sp] Catalase [E.C.1.11.1.6. Microbial] Ascorbate oxidase [EC.1.10.3.3. Acremonium sp.] Initial Concentration of Solution 100 mM, pH 6.6 (+25 °C) 0.7 mM ≥800 U/L ≥500 U/L ≥300 KU/L ≥3000 U/L
R2. Enzyme Reagent 2 N,N-Bis(2-hydroxyethyl)- 2-aminoethanesulfonic acid 4-Aminoantipyrine Peroxidase [E.C.1.11.1.7, Horse Radish, +25°C] Sodium Azide Surfactants Initial Concentration of Solution 100 mM, pH 7.0 (+25 °C) 4.0 mM ≥3500 U/L 0.05 w/v % 1.4 % w/v %
This looks like a 510(k) summary for an in vitro diagnostic (IVD) device, specifically for a Direct HDL Cholesterol (HDL) test system. Since IVD devices, especially Class I, do not typically involve AI or machine learning components as described in the prompt's questions, many of the requested fields (such as "number of experts used to establish ground truth", "adjudication method", "MRMC study", "standalone performance", "training set size", and "how ground truth for training set was established") are not applicable.
However, I can extract the relevant information regarding acceptance criteria and performance from the document.
1. Table of Acceptance Criteria and Reported Device Performance:
| Performance Characteristic | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Precision (CV) @ 28 mg/dL | (Implied by context, typically need to be within acceptable clinical limits/manufacturer specs; often <10% for clinical chemistry) | Total CV = 3.8% |
| Precision (CV) @ 44 mg/dL | (Implied by context) | Total CV = 4.1% |
| Precision (CV) @ 57 mg/dL | (Implied by context) | Total CV = 4.3% |
| Precision (CV) @ 39 mg/dL (Serum Pool) | (Implied by context) | Total CV = 3.4% |
| Precision (CV) @ 73 mg/dL (Serum Pool) | (Implied by context) | Total CV = 4.2% |
| Precision (CV) @ 62 mg/dL (Patient Pool) | (Implied by context) | Total CV = 3.6% |
| Precision (CV) @ 79 mg/dL (Linearity) | (Implied by context) | Total CV = 4.6% |
| Linearity (Deviation from Linearity) | Less than 5% | Correlation coefficient (r) = 0.998 (Strong linear correlation indicating deviation is likely within 5%) |
| Reportable Range | Established by linearity studies | 20 to 129 mg/dL |
| Interfering Substances (Hemoglobin) | No significant interference up to 1000 mg/dL | No significant interference up to 1000 mg/dL |
| Interfering Substances (Total Bilirubin) | No significant interference up to 60 mg/dL | No significant interference up to 60 mg/dL |
| Interfering Substances (Conjugate Bilirubin) | No significant interference up to 60 mg/dL | No significant interference up to 60 mg/dL |
| Interfering Substances (Triglycerides) | No significant interference up to 500 mg/dL | No significant interference up to 500 mg/dL |
| Interfering Substances (Intralipid®) | No significant interference up to 2000 mg/dL | No significant interference up to 2000 mg/dL |
| Interfering Substances (Ascorbic Acid) | No significant interference up to 6 mg/dL | No significant interference up to 6 mg/dL |
| Method Comparison (Correlation with Predicate) | (Implied: High correlation, e.g., r > 0.95 and slope close to 1, intercept close to 0) | Y = 1.01x - 0.75, r = 0.994 |
| Matrix Comparison (Serum vs. Lithium Heparin Plasma) | (Implied: High correlation, e.g., r > 0.95 and slope close to 1, intercept close to 0) | Y = 0.99x + 2.18, r = 0.993 |
2. Sample Size Used for the Test Set and Data Provenance:
- Precision/Reproducibility:
- Control material and human serum samples: 80 determinations per control level/serum pool (2 replicates/run x 2 runs/day x 20 days).
- Provenance: "unaltered human serum samples" and "control material." The documentation does not specify the country of origin of the human serum samples. The study design (testing over 20 non-consecutive days) suggests it's a prospective study for data collection, but the samples themselves could be retrospective.
- Linearity/Reportable Range:
- Samples: 11 levels, each run in replicates of five.
- Provenance: Low and high serum pool samples. Not specified for country of origin or retrospective/prospective.
- Detection Limit:
- Samples: 240 determinations (4 low-level samples) for LoD.
- Provenance: Not specified for country of origin or retrospective/prospective.
- Analytical Specificity (Interference):
- Samples: Spiked samples at 34.8 mg/dL and 70 mg/dL HDL Cholesterol concentrations. The number of individual samples is not explicitly stated.
- Provenance: Not specified for country of origin or retrospective/prospective.
- Method Comparison:
- Patient Samples: 103 serum patient samples.
- Provenance: Not specified for country of origin or retrospective/prospective.
- Matrix Comparison:
- Patient Samples: 45 matched patient sample pairs (serum and lithium heparin plasma).
- Provenance: Not specified for country of origin or retrospective/prospective.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:
- Not applicable as this is an in vitro diagnostic (IVD) device for quantitative biochemical analysis, not an AI/image-based diagnostic device requiring expert interpretation for ground truth. Ground truth is typically established by reference methods or validated laboratory measurements.
4. Adjudication Method for the Test Set:
- Not applicable for this type of IVD device.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size of How Much Human Readers Improve with AI vs. Without AI Assistance:
- Not applicable as this is an IVD device, not an AI-assisted diagnostic system involving human readers.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done:
- This device is a standalone in the sense that its performance characteristics (precision, linearity, interference, method comparison) are evaluated for the device itself as an assay system. There is no "algorithm only" vs. "human-in-the-loop" distinction because it's a quantitative chemical assay.
7. The Type of Ground Truth Used:
- For precision, linearity, and detection limit: The "ground truth" is implied to be the actual concentration of HDL Cholesterol, which is determined by the preparation of controls, spiked samples, and dilutions, or by the inherent properties of the samples themselves, and measured by the device and predicate.
- For analytical specificity (interference): The ground truth is the presence/absence of interferents at specific concentrations and their impact on the HDL measurement.
- For method comparison: The "ground truth" for comparison is the measurement obtained from the predicate device (Randox Laboratories Ltd, Direct HDL Cholesterol reagent, K982341). This represents a legally marketed device against which equivalence is demonstrated.
- For matrix comparison: The ground truth for comparison is the measurement obtained from serum samples when comparing to plasma samples.
8. The Sample Size for the Training Set:
- Not applicable in the context of machine learning/AI where "training set" has a specific meaning. For an IVD, the development and optimization of the reagent formulation and assay parameters would be an analogous "training" phase, but it doesn't involve a distinct "training set" of patient data in the AI sense.
9. How the Ground Truth for the Training Set Was Established:
- Not applicable for the same reasons as above. The "ground truth" for developing the assay itself would be established through chemical principles, optimization experiments, and validation against known standards and reference materials.
{0}------------------------------------------------
Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features the department's name encircling a symbol. The symbol is a stylized representation of three human profiles facing right, with flowing lines suggesting movement or connection. The text reads "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA".
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
RANDOX LABORATORIES, LTD. PAULINE ARMSTRONG QA/RA SENIOR MANAGER 55 DIAMOND ROAD CRUMLIN BT29 4QY GREAT BRITAIN
January 8, 2016
Re: K153435
Trade/Device Name: Direct HDL Cholesterol (HDL) Regulation Number: 21 CFR 862.1475 Regulation Name: Lipoprotein test system Regulatory Class: Class I, meets the limitations of exemption 21 CFR §862.9(c)(4) Product Code: LBS Dated: November 24, 2015 Received: November 27, 2015
Dear Ms. Armstrong:
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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, 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 Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
{1}------------------------------------------------
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. 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 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 Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Katherine Serrano -S
For :
Courtney Lias Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
{2}------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration
Indications for Use
Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement below.
510(k) Number (if known) K153435
Device Name DIRECT HDL CHOLESTEROL (HDL)
Indications for Use (Describe)
For the quantitative in vitro determination of HDL Cholesterol in serum and plasma. Such measurements are used in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis and renal diseases and for the assessment for the risk of developing cardiovascular disease.
This in vitro diagnostic device is intended for Rx Only.
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)
CONTINUE ON A SEPARATE PAGE IF NEEDED.
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
FORM FDA 3881 (8/14)
Di PSC Publishing Services (301) 443-6741
{3}------------------------------------------------
510(K) SUMMARY, DIRECT HDL CHOLESTEROL (HDL)
1. SAFETY AND EFFECTIVENESS AS REQUIRED BY 21 CFR 807.92 STATEMENT
This summary of the 510(k) safety and effectiveness information is being submitted in accordance with the requirement 21 CFR 807.92.
SUBMITTER NAME AND ADDRESS 2.
Name: Dr Pauline Armstrong
Address: Randox Laboratories Limited 55 Diamond Road, Crumlin, County Antrim, BT29 4QY, United Kingdom.
Telephone: +44 (0) 28 9442 2413 Fax: +44 (0) 28 9445 2912 E-mail: Pauline.Armstrong@randox.com
Date of Summary Preparation: January 6, 2016
3. 510k NUMBER, DEVICE PROPRIETARY NAME, COMMON NAME, PURPOSE FOR SUBMISSION, REGULATORY CLASSIFCATION, PANEL, PRODUCT CODE AND 21 CFR NUMBER
510k No: K153435
Device Proprietary Name: Direct HDL Cholesterol (HDL)
Common Name: Direct HDL Cholesterol (HDL)
Purpose for Submission: New Device
| ProductCode | Regulation Name | Classification | Regulation Section | Panel |
|---|---|---|---|---|
| LBS | Lipoprotein testsystem | Class I, meets thelimitation of exemption21 CFR §862.9(c)(4) | 21 CFR §862.1475Lipoprotein Test System | ClinicalChemistry(75) |
{4}------------------------------------------------
4. PREDICATE DEVICE PROPRIETARY NAMES AND 510 (k) NUMBERS
Predicate Device Proprietary Name:
Randox Laboratories Ltd, Direct HDL Cholesterol reagent
510 (k) Number: K982341
5. INTENDED USE
For the quantitative in vitro determination of HDL Cholesterol in serum and plasma. Such measurements are used in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis and various other liver and renal diseases, and for the assessment for the risk of developing cardiovascular disease.
6. DEVICE DESCRIPTION
The Direct HDL Cholesterol (HDL) kit assay consists of ready to use reagent solutions.
CATALOGUE NUMBER: CH8311
| R1. Enzyme Reagent 1 | 4 x 20 ml |
|---|---|
| R2. Enzyme Reagent 2 | 4 x 9 ml |
REAGENT COMPOSITION
| Contents | Initial Concentration of Solution | |
|---|---|---|
| R1. | Enzyme Reagent 1N,N-Bis(2-hydroxyethyl)-2-aminoethanesulfonic acidN-(2-hydroxy-3-Sulfopropyl)- 3,5-dimethoxyaniline, sodium salt (HDAOS)Cholesterol Esterase[E.C.3.1.1.13. Microorganism]Cholesterol Oxidase[E.C.1.1.3.6. Streptomyces sp]Catalase[E.C.1.11.1.6. Microbial]Ascorbate oxidase[EC.1.10.3.3. Acremonium sp.] | 100 mM, pH 6.6 (+25 °C)0.7 mM≥800 U/L≥500 U/L≥300 KU/L≥3000 U/L |
| R2. | Enzyme Reagent 2N,N-Bis(2-hydroxyethyl)-2-aminoethanesulfonic acid4-AminoantipyrinePeroxidase[E.C.1.11.1.7, Horse Radish, +25°C]Sodium AzideSurfactants | 100 mM, pH 7.0 (+25 °C)4.0 mM≥3500 U/L0.05 w/v %1.4 % w/v % |
{5}------------------------------------------------
MATERIALS REQUIRED BUT NOT PROVIDED
| Direct HDL-C/LDL-C Calibrator, CH 2673. (510(k) # K122126) | |||
|---|---|---|---|
| Randox Lipid Controls:- | Level 1 | LE 2661 or LE 2668 (510(k) # K022591) | |
| Level 2 | LE 2662 or LE 2669 (510(k) # K022591) | ||
| Level 3 | LE 2663 or LE 2670 (510(k) # K022591) | ||
| RX series Saline (Cat No SA 8396) |
7. PREDICATE DEVICE COMPARISON TABLE
Table 1 Comparison of HDL Cholesterol test system for the RX Daytona plus to predicate device
| CHARACTERISTICS | Direct HDL Cholesterol (HDL) forRX daytona plus(New Device)RandoxDirect HDL Cholesterol (K982341)(Predicate Device) | |
|---|---|---|
| Similarities | ||
| INTENDED USE | For the quantitative in vitro determination ofHDL Cholesterol in serum and plasma. Suchmeasurements are used in the diagnosis andtreatment of lipid disorders (such as diabetesmellitus),atherosclerosis and various otherliver and renal diseases, and for theassessment for the risk of developingcardiovascular disease. | Same |
| ASSAY PROTOCOL | Enzymatic Endpoint Method | Same |
| STORAGE(UNOPENED) | Reagents are stable up to the expiry datewhen stored unopened at +2 to +8°C | Same |
| SAMPLE TYPE | Serum and Plasma (Li Heparin) | Same |
| CONTROLFREQUENCY | Randox Lipid Control Sera, Level 1, Level 2and Level 3 are recommended for dailyquality control | Same |
| CALIBRATIONFREQUENCY | Every 28 days, with a change ofreagent lot or as indicated by quality controlprocedures. | Same |
{6}------------------------------------------------
| Differences | ||
|---|---|---|
| REAGENTCOMPOSITION | R1. Enzyme Reagent 1N,N-Bis(2-hydroxyethyl)- 100 mM, pH 6.6 (+25 °C)2-aminoethanesulfonic acidN-(2-hydroxy-3-Sulfopropyl)-3,5-dimethoxyaniline, sodium salt (HDAOS) 0.7 mMCholesterol Esterase ≥800 U/L[E.C.3.1.1.13. Microorganism]Cholesterol Oxidase ≥500 U/L[E.C.1.1.3.6. Streptomyces sp]Catalase ≥300 KU/L[E.C.1.11.1.6. Microbial]Ascorbate oxidase[EC.1.10.3.3. Acremonium sp.] ≥3000 U/LR2. Enzyme Reagent 2N,N-Bis(2-hydroxyethyl)- 100 mM, pH 7.0 (+25 °C)2-aminoethanesulfonic acid4-Aminoantipyrine 4.0 mMPeroxidase ≥3500 U/L[E.C.1.11.1.7, Horse Radish, +25°C]Sodium Azide 0.05 w/v %Surfactants 1.4% w/v% | R1. Enzyme Reagent 1N,N-Bis(2-hydroxyethyl)- 100 mM, pH 7.02-aminoethanesulfonic acidN-(2-hydroxy-3-Sulfopropyl)-3,5-dimethoxyaniline, sodium salt (HDAOS) 0.7 mMCholesterol Esterase ≥800 U/L[E.C.3.1.1.13. Microorganism]Cholesterol Oxidase ≥500 U/L[E.C.1.1.3.6. Nocardia]Catalase ≥300 KU/L[E.C.1.11.1.6. Bovine Liver]R2. Enzyme Reagent 2N,N-Bis(2-hydroxyethyl)- 100 mM, pH 7.02-aminoethanesulfonic acid4-Aminoantipyrine 4.0 mMPeroxidase ≥4 KU/L[E.C.1.11.1.7, Horse Radish, +25°C]Sodium Azide 0.05 w/v% |
| MEASURINGRANGE | 20 to 129 mg/dl |
8. TEST PRINCIPLE (1)
The assay consists of 2 distinct reaction steps:
-
- Elimination of chylomicron, VLDL-Cholesterol and LDL-Cholesterol by cholesterol esterase, cholesterol oxidase and subsequently catalase.
Cholesterolesterase Cholesterol ester cholesterol + fatty acid ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------Cholesterol oxidase ↑ Cholestenone + H2O2 Cholesterol + O2 ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------Catalase
- Elimination of chylomicron, VLDL-Cholesterol and LDL-Cholesterol by cholesterol esterase, cholesterol oxidase and subsequently catalase.
-
- Specific measurement of HDL-Cholesterol after release of HDL-Cholesterol by detergents in Reagent 2.
| Cholesterol ester | cholesterol + fatty acid |
|---|---|
| ------------------- | -------------------------- |
Cholesterolesterase
| Cholesterol + O2 | Cholestenone + H2O2 |
|---|---|
| ------------------ | --------------------- |
Cholesterol oxidase
{7}------------------------------------------------
2H₂O₂ + 4-AA + HDAOS
The intensity of the quinone imine dye produced is directly proportional to the cholesterol concentration when measured at 600 nm.
In the second reaction catalase is inhibited by sodium azide in Enzyme Reagent 2.
- Key: 4 AA 4 Aminoantipyrine HDAOS - N - (2 - hydroxy - 3 - sulfopropyl) -3,5 - dimethoxyaniline.
This assay uses a Rate method and a single point calibration.
- Izawa S., Okada M., Matsui H., and Horita Y. J. Medicine and Pharmaceutical Sci., 1385 - 1388, 37 (1997).
9. PERFORMANCE CHARACTERISTICS
Analytical performance:
a. Precision/Reproducibility:
Precision was evaluated consistent with C.L.S.I documents EP5-A2 Precision studies were performed by two operators on two RX Daytona plus systems using control material and unaltered human serum samples that were spiked with HDL cholesterol concentrations or diluted to achieve concentrations based on established ranges <40mg/dl undesirable, high risk HDL Cholesterol levels; ≥60 mg/dl desirable, low risk HDL cholesterol levels . Testing was conducted for two reagent lots of Direct HDL Cholesterol (HDL), one lot on each RX Daytona plus system, twice per day for 20 non-consecutive days. Two replicates per run were performed for each sample. The assay was calibrated on the first day of the study and no assay re-calibrations were required throughout the duration of the study. The results of Lot 1 which is representative of both lots of Direct HDL Cholesterol (HDL) reagent is summarized in the following table.
| Lot 1 | MEAN | Within Run | Among Run | Among Day | Total | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Method | Product | N | (mg/dl) | SD | CV | SD | CV | SD | CV | SD | CV |
| HDL | QC 1 | 80 | 28 | 0.03 | 3.7 | 0.00 | 0.0 | 0.01 | 0.9 | 0.03 | 3.8 |
| HDL | QC 2 | 80 | 44 | 0.04 | 3.8 | 0.00 | 0.0 | 0.02 | 1.5 | 0.05 | 4.1 |
| HDL | QC 3 | 80 | 57 | 0.06 | 4.0 | 0.00 | 0.0 | 0.02 | 1.7 | 0.06 | 4.3 |
| HDL | Serum Pool 2 | 80 | 39 | 0.02 | 1.8 | 0.02 | 2.1 | 0.02 | 1.9 | 0.03 | 3.4 |
Table 2 Precision Summary
{8}------------------------------------------------
| Lot 1 | MEAN | Within Run | Among Run | Among Day | Total | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Method | Product | N | (mg/dl) | SD | CV | SD | CV | SD | CV | SD | CV |
| HDL | Serum Pool 4 | 80 | 73 | 0.02 | 1.1 | 0.05 | 2.5 | 0.06 | 3.1 | 0.08 | 4.2 |
| HDL | Patient Pool | 80 | 62 | 0.03 | 2.1 | 0.03 | 1.7 | 0.04 | 2.3 | 0.06 | 3.6 |
| HDL | Linearity | 80 | 79 | 0.08 | 4.1 | 0.00 | 0.0 | 0.04 | 2.1 | 0.09 | 4.6 |
b. Linearity/assay reportable range:
Linearity studies have been carried out in accordance with C.L.S.I. standard EP6-A. Linearity studies were performed at 11 levels to determine the analytical range of an assay - that is the range where the reported result is a linear function to the analyte concentration (or where deviation from linearity is less than 5%).
The linearity samples were prepared at 11 levels. Randox used a low serum pool sample around 9.7 mg/dl analyte concentration and a serum pool with a high concentration approximately 125 - 130 mg/dl. The low and high pools were mixed to make nine intermediate levels. Each level was run in replicates of five on two lots of Direct HDL Cholesterol (HDL) reagent on one RX Daytona plus system. The observed values were compared to the expected values; the linear regression correlation between the expected values and the observed values for the samples with acceptable linearity are summarized in the following table:
Table 3 Linearity Summary including Regression equation and correlation coefficient.
| Analyte Tested | HDL Cholesterol(mg/dL) |
|---|---|
| Linear Regression | $Y = 1.06 - 2.80$ |
| r | 0.998 |
The reportable range of the assay is 20 to 129 mg/dl
The low and high end of the reportable assay range is based on the linearity. The Rx Daytona Plus analyzer has an auto-dilution feature that is automatically activated when measuring samples >129 mg/dL, which are diluted and remeasured to obtain values within the measuring range.
c. Traceability, Stability, Expected values (controls, calibrators, or methods):
Refer to K122126 Direct HDL/LDLCalibrator and K022591 Lipid Controls.
The Direct HDL-C/LDL-C Calibrator is traceable to an internal master reference material. Calibrators are value assigned using one instrument and multiple
{9}------------------------------------------------
repetitions. The mean, standard deviation, and % CV are calculated and evaluated against acceptance criteria.
The reagent system has not been tested or certified by the Cholesterol Reference Method Laboratory Network (CRMLN). The labeling contains language that the device has not been certified by the CRMLN.
d. Detection limit:
Sensitivity studies have been carried out in accordance with C.L.S.I. quideline EP17-A2 'Protocols for Determination of Limits of Detection and Limits of Quantification; Approved Guideline'. A Limit of Blank (L.o.B.), a Limit of Detection (L.o.D.) and a Limit of Quantification were performed on two lots of reagents tested by two operators on one RX Davtona Plus system.
The Limit of Detection (LoD) for Direct HDL Cholesterol (HDL) on the RX Daytona Plus is 0.73 mg/dl based on 240 determinations, with 4 low level samples.
The Limit of Blank (LoB) is 0.19 mg/dl.
The Limit of Quantitation (LoQ) is 7.1 mg/dl as determined by the lowest concentration detected with ≤20% imprecision.
e. Analytical Specificity:
Interference studies have been carried out in accordance with C.L.S.I. quideline EP7-A2 'Interference testing in clinical chemistry; Approved Guideline Second Edition' The effects of potential interferents were determined by calculating the mean value of the spiked interferent with the corresponding control solution. The spiked sample results were compared to control samples prepared without the potential interferents.
Acceptance Criteria: % of Control ± 10%
The following analytes were tested up to the levels indicated at HDL Cholesterol concentrations of 34.8 mq/dl and 70 mg/dl and found not to interfere:
| Haemoglobin | No significant interference up to 1000mg/dL |
|---|---|
| Total Bilirubin | No significant interference up to 60mg/dL |
| Conjugate Bilirubin | No significant interference up to 60mg/dL |
| Triglycerides | No significant interference up to 500mg/dL |
| Intralipid® | No significant interference up to 2000mg/dL |
| Ascorbic Acid | No significant interference up to 6mg/dL |
{10}------------------------------------------------
f. Method comparison with predicate device:
Correlation studies were carried out in accordance with C.L.S.I. guideline EP9-A2 'Method Comparison and Bias Estimation Using Patient Samples: Approved Guideline - Second Edition'.
103 serum patient samples spanning the range 23 to 118 mg/dl were tested by two operators on two lots of Direct HDL Cholesterol (HDL) reagent on one RX Daytona plus analyzer and one RX Imola system across 3 working days with each sample tested in singlicate. The test method was compared to the predicate device and the following linear regression equation was obtained:
Y = 1.01x - 0.75 Correlation coefficient of r = 0.994
q. Matrix comparison:
Matrix method comparisons for the Direct HDL Cholesterol (HDL) assay was tested by one operator on one RX Daytona plus system and was assessed for two lots of Direct HDL Cholesterol (HDL) reagents. Both serum and lithium heparin plasma were tested to determine whether method accuracy with plasma specimens are equivalent to serum results and that lithium heparin plasma does not interfere with either the method or the system.
Direct HDL Cholesterol (HDL) matrix comparison on the RX Daytona plus (Lithium Heparin)
Patient samples were drawn in matched pairs – one sample serum (x) and the second sample lithium heparin plasma (y). 45 matched patient sample pairs were analyzed spanning the 28 to 106 mg/dl and the following linear regression equation was obtained:
Y = 0.99x + 2.18 Correlation coefficient of r = 0.993
Expected values/Reference range:
Referenced from literature
{11}------------------------------------------------
Table 4 Reference Ranges
| Analyte | Serum |
|---|---|
| HDL Cholesterol (2) | < 40 mg/dl Undesirable, high risk HDL cholesterol levels≥60 mg/dl Desirable, low risk HDL cholesterol levels |
- Third Report of the National Cholesterol Education Programme (NCEP) Expert Panel on Detection, Evaluation and treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). NIH Publication No. 02-5215 September 2002
10. CONCLUSION
Testing results indicate that the proposed device is substantially equivalent to the predicate device.
§ 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.