(200 days)
For the quantitative in vitro determination of Cholesterol in serum and plasma. Cholesterol measurements are used in the diagnosis and treatments of disorders involving excess cholesterol in the blood and lipoprotein metabolism disorders.
The Cholesterol kit assay consists of ready to use reagent solutions.
CATALOGUE NUMBER: CH8310
R1. Reagent 4 x 20 ml
REAGENT COMPOSITION
Contents: R1. Reagent 4-Aminoantipyrine, Phenol, Peroxidase (E.C.1.11.1.7, Horse Radish, +25°C), Cholesterol esterase (E.C.3.1.1.13. Pseudomonas, +37°C), Cholesterol oxidase (E.C.1.1.3.6. Nocardia, +37°C), Sodium Azide
Concentrations in the Test: 0.25 mmol/l, 6.00 mmol/l, >=0.50 U/ml, >= 0.20 U/ml, >=0.10 U/ml, 0.09%
MATERIALS REQUIRED BUT NOT PROVIDED: Randox Assayed Multisera Level 2 (Cat. No. HN 1530) and Level 3 (Cat. No. HE 1532); 510(k) # K942458, Randox Calibration Serum Level 3 (Cat. No. CAL 2351); 510(k) # K053153, RX series Saline (Cat. No. SA 8396)
Here's a breakdown of the acceptance criteria and study information for the Randox Laboratories Ltd. Cholesterol device, based on the provided FDA 510(k) summary:
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state "acceptance criteria" for all tests in a single table, but rather presents the performance results of various analytical studies that demonstrate the device's capability. I've compiled the relevant performance data from the document into a table, noting the implicit acceptance measures (e.g., meeting CLSI guidelines, certain correlation coefficients, or imprecision percentages).
| Metric / Study | Acceptance Criteria (Implicit) | Reported Device Performance |
|---|---|---|
| Precision | Performed consistent with CLSI EP5-A2. Total CV % for controls and patient samples to be within acceptable limits (typically < 10% for diagnostic assays, often tighter for specific analytes, but not explicitly stated here for cholesterol in the context of acceptance). | Lot 1:- Control (283 mg/dl): Total CV 2.0%- Control (307 mg/dl): Total CV 1.8%- Control (190 mg/dl): Total CV 2.0%- Patient Sample (176 mg/dl): Total CV 2.5%- Patient Sample (226 mg/dl): Total CV 2.4%- Patient Sample (270 mg/dl): Total CV 2.1%- Patient Sample (586 mg/dl): Total CV 2.0%- Sensitivity Pool (33.2 mg/dl): Total CV 8.8%Lot 2:- Control (285 mg/dl): Total CV 2.0%- Control (310 mg/dl): Total CV 2.3%- Control (192 mg/dl): Total CV 2.4%- Patient Sample (177 mg/dl): Total CV 2.7%- Patient Sample (228 mg/dl): Total CV 2.7%- Patient Sample (272 mg/dl): Total CV 2.7%- Patient Sample (592 mg/dl): Total CV 1.9%- Sensitivity Pool (32.4 mg/dl): Total CV 10.3% |
| Linearity / Reportable Range | Performed consistent with CLSI EP6-A. Deviation from linearity < 5%. | Linearity: Up to 618 mg/dlReportable Range: 25 – 618 mg/dlRegression (approx. from graph): Slope ~0.99, Intercept ~-3.71, r = 0.999, Syx = 4.85 |
| Detection Limit (LoD) | Performed consistent with CLSI EP17-A2. | LoD: 6.31 mg/dl |
| Limit of Blank (LoB) | Performed consistent with CLSI EP17-A2. | LoB: 3.1 mg/dl |
| Limit of Quantitation (LoQ) | Lowest concentration detected with ≤20% imprecision. | LoQ: 23.2 mg/dl |
| Analytical Specificity (Interference) | % of Control ± 10% for tested interferents. | Haemoglobin: No significant interference up to 750mg/dLTotal Bilirubin: No significant interference up to 60mg/dLConjugate Bilirubin: No significant interference up to 60mg/dLIntralipid®: No significant interference up to 1000mg/dLAscorbic Acid: No significant interference up to 6mg/dL |
| Method Comparison (vs. Predicate) | Performed consistent with CLSI EP9-A2. High correlation coefficient (typically r > 0.975 for quantitative assays) and acceptable regression equation (slope close to 1, intercept close to 0) indicating substantial equivalence. | Serum samples (vs. Predicate): Y = 1.00x - 4.77, r = 0.997 |
| Matrix Comparison (Li Heparin) | High correlation coefficient (typically r > 0.975) and acceptable regression equation (slope close to 1, intercept close to 0) demonstrating equivalence between serum and lithium heparin plasma. | Serum vs. Li Heparin: Y = 1.01x - 6.54, r = 0.997 |
| Matrix Comparison (K₂EDTA) | High correlation coefficient (typically r > 0.975) and acceptable regression equation (slope close to 1, intercept close to 0) demonstrating equivalence between serum and K₂EDTA plasma. | Serum vs. K₂EDTA: Y = 0.99x + 2.85, r = 0.998 |
2. Sample Sizes and Data Provenance for the Test Set
- Precision/Reproducibility:
- Controls: Not explicitly stated as "sample size" but data is reported for commercial control materials (717UE, 724UE, 952UN).
- Patient Samples: 4 concentrations of unaltered human serum samples (3 diluted, 1 spiked for Linearity Pool, 1 Sensitivity Pool). Each sample run in 2 replicates per run, twice per day for 20 non-consecutive days, using 2 reagent lots on 2 RX Daytona plus systems.
- Data Provenance: "unaltered human serum samples" implies human origin, likely retrospective for spiking/dilution. No country of origin is specified.
- Linearity/Assay Reportable Range:
- Sample Size: 11 levels of samples covering the measuring range. Each level run in 5 replicates.
- Data Provenance: "linearity samples" were prepared. Implies in-vitro prepared samples to cover the range, likely based on human serum/plasma.
- Detection Limit (LoD), Limit of Blank (LoB), Limit of Quantitation (LoQ):
- Sample Size: LoD was based on 240 determinations with 4 low-level samples.
- Data Provenance: Not specified, but generally prepared samples for low-level determination.
- Analytical Specificity (Interference):
- Sample Size: Not explicitly stated for the number of interferent samples, but tested at Cholesterol concentrations of 150 mg/dl and 250 mg/dl for each interferent.
- Data Provenance: Prepared samples spiked with interferents.
- Method Comparison with Predicate Device:
- Sample Size: 107 serum patient samples.
- Data Provenance: "serum patient samples" spanning 25 to 599 mg/dl. Retrospective. No country of origin specified.
- Matrix Comparison:
- Sample Size (Lithium Heparin): Minimum of 54 matched patient sample pairs (serum vs. lithium heparin plasma).
- Sample Size (Potassium 2 EDTA): Minimum of 50 matched patient sample pairs (serum vs. potassium 2 EDTA plasma).
- Data Provenance: "Patient samples were drawn in matched pairs". Retrospective from human subjects. No country of origin specified.
3. Number of Experts and Qualifications for Ground Truth for the Test Set
This device is an in vitro diagnostic (IVD) for quantitative measurement of cholesterol. The "ground truth" for such devices is established by precise laboratory reference methods or established commercially available controls and calibrators with known values.
- No "experts" in the sense of radiologists or pathologists establishing ground truth as would be the case for imaging devices.
- Ground truth is established by:
- Reference materials (e.g., NIST 1952a for the calibrators, mentioned under traceability).
- Established analytical methods used by the predicate device and in clinical laboratories.
- CLSI guidelines for experimental design and data analysis.
4. Adjudication Method for the Test Set
Not applicable for this type of quantitative IVD device. Adjudication methods (like 2+1, 3+1) are typically used for qualitative or semi-quantitative assessments, especially in imaging or pathology, where human expert discrepancy resolution is needed. For quantitative chemical measurements, the ground truth is often numerical and objectively determined.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No. This is an in vitro diagnostic device for chemical analysis of cholesterol, not an imaging or qualitative assessment device involving human readers. Therefore, an MRMC study is not relevant.
6. Standalone (i.e., algorithm only without human-in-the-loop performance) Study
Yes, the entire performance evaluation presented is a standalone study of the device (Cholesterol assay on the RX Daytona plus system). The device performs the analytical measurement autonomously once the sample is loaded. The studies demonstrate the analytical performance of the device itself.
7. Type of Ground Truth Used
The ground truth for the performance studies is multi-faceted:
- Reference Materials: Randox Calibration Serum Level 3 is traceable to Cholesterol reference material NIST 1952a. This is a primary ground truth for calibration and accuracy.
- Predicate Device: For method comparison studies, the predicate device (Randox Cholesterol reagent, K923504) serves as a comparative ground truth, aiming to demonstrate substantial equivalence rather than absolute biological truth.
- CLSI Guidelines: The studies adhere to CLSI (Clinical and Laboratory Standards Institute) guidelines (EP5-A2 for precision, EP6-A for linearity, EP17-A2 for detection limits, EP9-A2 for method comparison), which represent an industry-accepted "ground truth" for how these analytical performance characteristics should be determined and evaluated.
- Prepared Samples: For linearity, sensitivity, detection limits, and interference, samples were prepared to known concentrations or spiked with known substances to create specific "ground truth" scenarios.
8. Sample Size for the Training Set
There is no mention of a "training set" in the context of machine learning or AI, as this device is a traditional in vitro diagnostic reagent system, not an AI/ML-based device.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no training set for an AI/ML algorithm in this context.
{0}------------------------------------------------
Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized symbol that resembles three human profiles facing to the right, stacked on top of each other.
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 MANAGER 55 DIAMOND ROAD CRUMLIN BT29 4QY GREAT BRITAN
September 29, 2015
Re: K150654
Trade/Device Name: Cholesterol Regulation Number: 21 CFR 862.1175 Regulation Name: Cholesterol (total) test system Regulatory Class: Class I, meets the limitation of exemption 21 CFR §862.9(c)(4) Product Code: CHH Dated: September 21, 2015 Received: September 24, 2015
Dear Dr. 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 (QS) 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 H. 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
510(k) Number (if known) K150654
Device Name Cholesterol
Indications for Use (Describe)
For the quantitative in vitro deternination of Cholesterol in serum and plasma. Cholesterol measurements are used in the diagnosis and treatments of disorders involving excess cholesterol in the blood and lipoprotein metabolism disorders.
Type of Use (Select one or both, as applicable)
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 Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement below.
{3}------------------------------------------------
510(K) SUMMARY, CHOLESTEROL REAGENT
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: September 29, 2015
3. 510k NUMBER, DEVICE PROPRIETARY NAME, COMMON NAME, PURPOSE FOR SUBMISSION, REGULATORY CLASSIFCATION, PANEL, PRODUCT CODE AND 21 CFR NUMBER
510k No: K150654
Device Proprietary Name: Cholesterol
Common Name: Cholesterol
Purpose for Submission: New Device
| ProductCode | Regulation Name | Classification | Regulation Section | Panel |
|---|---|---|---|---|
| CHH | Cholesterol (Total)test system | Class I, meets thelimitation of exemption21 CFR §862.9(c)(4) | 21 CFR §862.1175Cholesterol (total) TestSystem | ClinicalChemistry(75) |
{4}------------------------------------------------
4. PREDICATE DEVICE PROPRIETARY NAMES AND 510 (k) NUMBERS
Predicate Device Proprietary Name:
Randox Laboratories Ltd, Cholesterol reagent
510 (k) Number: K923504
5. INTENDED USE
For the quantitative in vitro determination of Cholesterol in serum and plasma. Cholesterol measurements are used in the diagnosis and treatments of disorders involving excess cholesterol in the blood and lipid and lipoprotein metabolism disorders.
6. DEVICE DESCRIPTION
The Cholesterol kit assay consists of ready to use reagent solutions.
CATALOGUE NUMBER: CH8310
R1. Reagent 4 x 20 ml
REAGENT COMPOSITION
| Contents | Concentrations in the Test |
|---|---|
| R1. Reagent4-AminoantipyrinePhenolPeroxidase(E.C.1.11.1.7, Horse Radish, +25°C)Cholesterol esterase(E.C.3.1.1.13. Pseudomonas, +37°C)Cholesterol oxidase(E.C.1.1.3.6. Nocardia, +37°C)Sodium Azide | 0.25 mmol/l6.00 mmol/l≥0.50 U/ml≥ 0.20 U/ml≥0.10 U/ml0.09% |
MATERIALS REQUIRED BUT NOT PROVIDED
Randox Assayed Multisera Level 2 (Cat. No. HN 1530) and Level 3 (Cat. No. HE 1532); 510(k) # K942458 Randox Calibration Serum Level 3 (Cat. No. CAL 2351); 510(k) # K053153 RX series Saline (Cat. No. SA 8396)
{5}------------------------------------------------
7. PREDICATE DEVICE COMPARISON TABLE
Table 1 Comparison of Cholesterol test system for the RX Daytona plus to predicate device
| CHARACTERISTICS | Cholesterol Assay forRX daytona plus(New Device) | RandoxCholesterol (K923504)(Predicate Device) | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Similarities | |||||||||
| INTENDED USE | For the quantitative in vitro determination ofCholesterol in serum and plasma. Cholesterolmeasurements are used in the diagnosis andtreatments of disorders involving excesscholesterol in the blood and lipid andlipoprotein metabolismdisorders | 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 | SerumPlasma (Li Heparin & K2 EDTA) | Same | |||||||
| CONTROLFREQUENCY | Randox assayed human multisera Level 2 & 3Two levels of control should be assayed atleast once a day | Same | |||||||
| CALIBRATIONFREQUENCY | Every 28 days, with a change ofreagent lot or as indicated by quality controlprocedures. | Same |
| Differences | ||
|---|---|---|
| REAGENTCOMPOSITION | R1. Reagent4-Aminoantipyrine 0.25 mmol/lPhenol 6.00 mmol/lPeroxidase ≥0.50 U/ml(E.C.1.11.1.7, Horse Radish, +25°C)Cholesterol esterase ≥ 0.20 U/ml(E.C.3.1.1.13. Pseudomonas, +37°C)Cholesterol oxidase ≥ 0.10 U/ml(E.C.1.1.3.6. Nocardia, +37°C)Sodium Azide 0.09% | R1. ReagentPipes Buffer 80 mmol/l, pH 6.84-Aminoantipyrine 0.25 mmol/lPhenol 6 mmol/lPeroxidase ≥0.5 U/ml(E.C.1.11.1.7, Horse Radish, +25°C)Cholesterol esterase ≥0.15 U/ml(E.C.3.1.1.13. Pseudomonas, 37°C)Cholesterol oxidase ≥0.10 U/ml(E.C.1.1.3.6. Nocardia, 37°C) |
| MEASURINGRANGE | 25 to 618 mg/dl | 0.55 to 750 mg/dl |
{6}------------------------------------------------
8. TEST PRINCIPLE (1)
The cholesterol is determined after enzymatic hydrolysis and oxidation. The indicator quinoneimine is formed from hydrogen peroxide and 4-aminoantipyrine in the presence of phenol and peroxidase.
Image /page/6/Figure/2 description: This image shows three chemical reactions. The first reaction shows cholesterol ester and H20 reacting to form cholesterol and fatty acids, with cholesterol-esterase as the catalyst. The second reaction shows cholesterol and O2 reacting to form cholestene-3-one and H202, with cholesterol oxidase as the catalyst. The third reaction shows 2H202, phenol, and 4-Aminoantipyrine reacting to form quinoneimine and 4H20, with peroxidase as the catalyst.
- Abell, L.L, Levey, B.B., Brodie B.B., et al, J. Biol Chem 195 : 357, 1952
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 Cholesterol concentrations or diluted to achieve concentrations based on established ranges <200mg/dl desirable cholesterol level ; 200 - 239 mg/dl borderline high cholesterol level and ≥240 mg/dl high cholesterol levels . Testing was conducted for two reagent lots of Cholesterol, 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. No assay re-calibrations were required throughout the duration of the study. The results are summarized in the following tables.
| System: RX Daytona Plus | Within Run | Among Run | Among Day | Total | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| MethodLot 1 | Product | MEAN(mg/dl) | SD | CV(%) | SD | CV(%) | SD | CV(%) | SD | CV(%) |
| Cholesterol | 717UE | 283 | 5.56 | 2.0 | 0.00 | 0.0 | 0.82 | 0.3 | 5.62 | 2.0 |
| Cholesterol | 724UE | 307 | 5.02 | 1.6 | 0.98 | 0.3 | 2.44 | 0.8 | 5.66 | 1.8 |
| Cholesterol | 952UN | 190 | 3.33 | 1.8 | 1.33 | 0.7 | 1.02 | 0.5 | 3.73 | 2.0 |
Table 2 Precision Summary
{7}------------------------------------------------
| System: RX Daytona Plus | Within Run | Among Run | Among Day | Total | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| MethodLot 1 | Product | MEAN(mg/dl) | SD | CV(%) | SD | CV(%) | SD | CV(%) | SD | CV(%) |
| Cholesterol | Level 1(DilutedPatientSample | 176 | 3.30 | 1.9 | 2.42 | 1.4 | 1.55 | 0.9 | 4.37 | 2.5 |
| Cholesterol | Level 2(DilutedPatientSample | 226 | 3.95 | 1.7 | 2.79 | 1.2 | 2.22 | 1.0 | 5.32 | 2.4 |
| Cholesterol | Level 3(DilutedPatientSample | 270 | 3.95 | 1.5 | 4.09 | 1.5 | 0.00 | 0.0 | 5.69 | 2.1 |
| Cholesterol | LinearityPool(SpikedPatientSample) | 586 | 0.03 | 1.2 | 9.30 | 1.6 | 0.00 | 0.0 | 11.63 | 2.0 |
| Cholesterol | SensitivityPool | 33.2 | 0.28 | 3.5 | 2.45 | 7.4 | 1.09 | 3.3 | 2.93 | 8.8 |
| System: RX Daytona Plus | Within Run | Among Run | Among Day | Total | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| MethodLot 2 | Product | MEAN(mg/dl) | SD | CV(%) | SD | CV(%) | SD | CV(%) | SD | CV(%) |
| Cholesterol | 717UE | 285 | 4.22 | 1.5 | 2.68 | 0.9 | 2.49 | 0.9 | 5.59 | 2.0 |
| Cholesterol | 724UE | 310 | 5.52 | 1.8 | 3.94 | 1.3 | 2.47 | 0.8 | 7.22 | 2.3 |
| Cholesterol | 952UN | 192 | 3.33 | 1.7 | 3.29 | 1.7 | 0.00 | 0.0 | 4.68 | 2.4 |
| Cholesterol | Level 1(DilutedPatientSample | 177 | 3.56 | 2.0 | 1.57 | 0.9 | 2.83 | 1.6 | 4.82 | 2.7 |
| Cholesterol | Level 2(DilutedPatientSample | 228 | 4.04 | 1.8 | 4.70 | 2.1 | 0.00 | 0.0 | 6.20 | 2.7 |
| Cholesterol | Level 3(DilutedPatientSample | 272 | 3.84 | 1.4 | 6.27 | 2.3 | 0.00 | 0.0 | 7.35 | 2.7 |
| Cholesterol | LinearityPool(SpikedPatientSample) | 592 | 6.76 | 1.1 | 9.11 | 1.5 | 0.00 | 0.0 | 11.3 | 1.9 |
| Cholesterol | SensitivityPool | 32.4 | 1.17 | 3.6 | 3.14 | 9.7 | 0.00 | 0.0 | 3.35 | 10.3 |
{8}------------------------------------------------
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 covering the measuring range. Each level was run in replicates of five on two lots of cholesterol reagent on one RX Daytona plus system. The results are summarized in the following table:
Table 3 Linearity Summary including Regression equation and correlation co-efficient.
Image /page/8/Figure/4 description: The image is a graph titled "Linearity". The x-axis is labeled "Level" and ranges from 0 to 12. The y-axis is labeled "Mean Result" and ranges from 0 to 700. The graph contains a scatter plot of mean values, a solid line representing a linear fit to levels 1-5, and a dashed line representing a linear fit to levels 2-6.
| Slope | 0.99 |
|---|---|
| Intercept | -3.71 |
| r | 0.999 |
| Syx | 4.85 |
Linearity Summary
| Analvte | Linearitv | Reportable Range | ||
|---|---|---|---|---|
| Cholesterol | 618 mg/dl | 25 – 618 mg/dl |
The RX Daytona Plus analyzer has an auto-dilution feature that is automatically activated when measuring samples >618mg/dl, which are diluted and remeasured to obtain values within the measuring range.
{9}------------------------------------------------
c. Traceability, Stability, Expected values (controls, calibrators, or methods):
Refer to K053153 Calibrator and K942458 Control for Cholesterol.
Randox Calibration Serum Level 3 is traceable to Cholesterol reference material NIST 1952a.
d. Detection limit:
Sensitivity studies have been carried out in accordance with C.L.S.I. guideline 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 Daytona Plus system.
The Limit of Detection (LoD) for Cholesterol on the RX Daytona Plus is 6.31 mg/dl based on 240 determinations, with 4 low level samples.
The Limit of Blank (LoB) is 3.1 mg/dl.
The Limit of Quantitation (LoQ) is 23.2 mg/dl as determined by the lowest concentration detected with ≤20% imprecision.
e. Analytical Specificity:
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 Cholesterol concentrations of 150 mg/dl and 250 mg/dl and found not to interfere:
| Haemoglobin | No significant interference up to 750mg/dL |
|---|---|
| Total Bilirubin | No significant interference up to 60mg/dL |
| Conjugate Bilirubin | No significant interference up to 60mg/dL |
| Intralipid® | No significant interference up to 1000mg/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'.
107 serum patient samples spanning the range 25 to 599 mg/dl were tested by two operators on two lots of cholesterol reagent on two RX Daytona plus analyzers 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 = 1.00x — 4.77 Correlation coefficient of r = 0.997
q. Matrix comparison:
Matrix method comparisons for the cholesterol assay was tested by one operator on one RX Daytona plus system and was assessed for two lots of cholesterol reagents. Both serum and lithium heparin and K₂EDTA plasma were tested to determine whether method accuracy with plasma specimens are equivalent to serum results and that lithium heparin and K₂EDTA plasma does not interfere with either the method or the system.
Cholesterol 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). A minimum of 54 matched patient sample pairs were analyzed spanning the 25 to 613 mg/dl and the following linear regression equation was obtained:
Y = 1.01x - 6.54 Correlation coefficient of r = 0.997
Cholesterol matrix comparison on the RX Daytona plus (Potassium 2 EDTA)
Patient samples were drawn in matched pairs – one sample serum (x) and the second sample potassium 2 EDTA plasma (y). A minimum of 50 matched patient sample pairs were analyzed spanning the 29 to 603 mg/dl and the following linear regression equation was obtained:
Y = 0.99x + 2.85 Correlation coefficient of r = 0.998
{11}------------------------------------------------
Expected values/Reference range:
Referenced from literature
Table 4 Reference Ranges
| Analyte | Serum |
|---|---|
| Cholesterol (2) | < 200 mg/dl Desirable blood cholesterol200 – 239 mg/dl Borderline-high blood cholesterol$\ge$ 240 mmol/l High blood cholesterol |
- 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). JAMA Publication, Vol 285, No. 19, P2486 - 2497; 2001.
10. CONCLUSION
Testing results indicate that the proposed device is substantially equivalent to the predicate device.
§ 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.