(568 days)
The Cholesterol2 assay is used for the quantitation of cholesterol in human serum or plasma on the ARCHITECT c System. The Cholesterol2 assay is to be used as an aid in the diagnosis and treatment of disorders involving excess cholesterol in the blood and lipid and lipoprotein metabolism disorders.
The Cholesterol2 assay is an automated clinical chemistry assay for the quantitation of cholesterol in human serum or plasma on the ARCHITECT c System. Cholesterol esters are enzymatically hydrolyzed by cholesterol esterase to cholesterol and free fatty acids. Free cholesterol, including that originally present, is then oxidized by cholesterol oxidase to cholest-4-ene-3-one and hydrogen peroxide. The hydrogen peroxide oxidatively couples with N,N-Bis(4-sulfobutyl)-3-methylaniline (TODB) and 4-aminoantipyrine to form a chromophore (quinoneimine dye) which is quantitated at 604 nm.
The provided text describes the Abbott Cholesterol2 assay, an in vitro diagnostic device for quantifying cholesterol in human serum or plasma.
Here's an analysis of the acceptance criteria and study data:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria for each performance characteristic. Instead, it presents the results of various studies as proof of device performance. The table below summarizes the reported performance, which implicitly serves as the "met" criteria.
| Performance Characteristic | Reported Device Performance (Cholesterol2) |
|---|---|
| Analytical Measuring Interval (AMI) | 5-748 mg/dL |
| Extended Measuring Interval (EMI) | 748-2992 mg/dL |
| Reportable Interval | 2-2992 mg/dL |
| Precision | |
| Control Level 1 (251 mg/dL) | SD: 1.9 mg/dL (Within-Run), 2.6-3.1 mg/dL (Within-Laboratory); %CV: 0.7% (Within-Run), 1.0-1.2% (Within-Laboratory) |
| Control Level 2 (106 mg/dL) | SD: 1.0 mg/dL (Within-Run), 1.3-1.7 mg/dL (Within-Laboratory); %CV: 1.0% (Within-Run), 1.2-1.6% (Within-Laboratory) |
| Panel A (21 mg/dL) | SD: 0.6 mg/dL (Within-Run), 0.7-0.8 mg/dL (Within-Laboratory); %CV: 3.0% (Within-Run), 3.2-4.1% (Within-Laboratory) |
| Panel B (237 mg/dL) | SD: 2.8 mg/dL (Within-Run), 3.7-4.9 mg/dL (Within-Laboratory); %CV: 1.2% (Within-Run), 1.5-2.0% (Within-Laboratory) |
| Panel C (718 mg/dL) | SD: 6.4 mg/dL (Within-Run), 4.6-6.9 mg/dL (Within-Laboratory); %CV: 0.9% (Within-Run), 0.7-1.0% (Within-Laboratory) |
| Limit of Blank (LoB) | 0 mg/dL |
| Limit of Detection (LoD) | 2 mg/dL |
| Limit of Quantitation (LoQ) | 5 mg/dL (at 20% CV maximum allowable precision) |
| Linearity | Linear across the analytical measuring interval of 5 to 748 mg/dL |
| Interference (Endogenous) | |
| Conjugated Bilirubin (7 mg/dL) | No significant interference (within ± 10%) |
| Unconjugated Bilirubin (11 mg/dL) | No significant interference (within ± 10%) |
| Hemoglobin (1000 mg/dL) | No significant interference (within ± 10%) |
| Total Protein (15 g/dL) | No significant interference (within ± 10%) |
| Conjugated Bilirubin (40 mg/dL) | Interference: -39% at 150 mg/dL analyte, -31% at 220 mg/dL analyte |
| Unconjugated Bilirubin (16 mg/dL) | Interference: -11% at 150 mg/dL analyte |
| Interference (Exogenous) | |
| Acetaminophen (160 mg/L) | No significant interference |
| Acetylcysteine (150 mg/L) | No significant interference |
| Acetylsalicylic acid (30 mg/L) | No significant interference |
| Aminoantipyrine (40 mg/L) | No significant interference |
| Ampicillin-Na (80 mg/L) | No significant interference |
| Biotin (4250 ng/mL) | No significant interference |
| Ca-dobesilate (60 mg/L) | No significant interference |
| Cefotaxime (53 mg/dL) | No significant interference |
| Cefoxitin (6600 mg/L) | No significant interference |
| Cyclosporine (2 mg/L) | No significant interference |
| Desacetylcefotaxime (6 mg/dL) | No significant interference |
| Dipyrone (100 mg/L) | No significant interference |
| Dobutamine (0.2 mg/dL) | No significant interference |
| Doxycycline (20 mg/L) | No significant interference |
| Ibuprofen (220 mg/L) | No significant interference |
| Intralipid (1050 mg/dL) | No significant interference |
| Levodopa (8 mg/L) | No significant interference |
| Methotrexate (140 mg/dL) | No significant interference |
| Metronidazole (130 mg/L) | No significant interference |
| Methylaminoantipyrine (40 mg/L) | No significant interference |
| Methyldopa (20 mg/L) | No significant interference |
| N-Acetyl-p-benzoquinone (NAPQI) (20 mg/L) | No significant interference |
| Phenylbutazone (330 mg/L) | No significant interference |
| Phenytoin (6 mg/dL) | No significant interference |
| Rifampicin (50 mg/L) | No significant interference |
| Sodium heparin (4 U/mL) | No significant interference |
| Sulpiride (15 mg/L) | No significant interference |
| Theophylline (60 mg/L) | No significant interference |
| Ascorbic acid (60 mg/L) | Interference: -10% at 150 mg/dL analyte |
| Intralipid (2000 mg/dL) | Interference: -27% at 150 mg/dL analyte, -22% at 220 mg/dL analyte |
| Methyldopa (30 mg/L) | Interference: -14% at 150 mg/dL analyte |
| Method Comparison (vs. Predicate) | |
| Serum (n=138) | Correlation Coefficient: 1.00; Intercept: 0.41; Slope: 0.98 (Range: 7-684 mg/dL) |
| Tube Type Suitability | Acceptable for Serum, Serum separator, Lithium heparin, Lithium heparin separator, Sodium heparin tubes. |
| Dilution Verification | Automated dilution protocol (1:5.97) and manual dilution procedure (1:4) evaluated. (Performance details not provided in summary). |
| Traceability | Traceable to National Reference System for Cholesterol (Abell-Kendall reference method in a CDC-Certified CRMLN). |
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
- Precision Study: 2 controls and 3 human serum panels were tested. Each sample was tested in duplicate, twice per day for 20 days. This means 80 measurements per sample (2 duplicates x 2 times/day x 20 days).
- Lower Limits of Measurement Study: n ≥ 60 replicates for LoB, LoD, and LoQ determinations. They used low-analyte level samples and zero-analyte samples.
- Linearity Study: The number of samples for the linearity study is not explicitly stated, but it covered the range of 5 to 748 mg/dL.
- Interference Studies: Each endogenous substance was tested at 2 analyte levels (approximately 150 mg/dL and 220 mg/dL). Exogenous substances were tested at various specified interferent levels. The number of samples for each interferent is not provided.
- Method Comparison Study: 138 serum samples were used.
- Tube Type Study: Samples were collected from a minimum of 40 donors.
- Dilution Verification: 8 human serum samples.
Data Provenance: The document does not specify the country of origin of the data or whether the studies were retrospective or prospective. Given the context of medical device regulatory submission, these are typically prospective studies conducted in a controlled laboratory environment. The "human serum panels" and "human serum samples" imply human-derived biological samples.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)
This device is an in vitro diagnostic (IVD) chemistry assay. The concept of "experts establishing ground truth" as it applies to image interpretation or clinical diagnosis by medical professionals (like radiologists) does not directly apply here in the same way.
For IVDs like this, the "ground truth" or reference values are established through:
- Reference methods: The Cholesterol2 reagent is certified to be traceable to the National Reference System for cholesterol, against the Abell-Kendall reference method in a CDC-Certified Cholesterol Reference Method Laboratory Network (CRMLN). The Abell-Kendall method is considered the gold standard for cholesterol measurement.
- Analytically Validated Methods: For values outside the AMI but within the EMI, samples were "value assigned using the analytically validated method."
- Known concentrations: For studies like linearity, spiked samples with known concentrations are used.
Therefore, the "experts" are the methodologists and laboratory professionals overseeing and validating the reference methods and the analytical validation processes. No specific number or qualification of clinical experts (e.g., radiologists) is relevant for establishing the ground truth for a quantitative chemistry assay.
This is a standalone performance evaluation of the assay itself, demonstrating its analytical accuracy, precision, and robustness.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
The concept of "adjudication" (e.g., 2+1, 3+1 where multiple human readers agree or have a tie-breaker by an expert) is not applicable to this type of quantitative diagnostic assay. The results are numerical values generated by the automated instrument and reagents. Deviations or discrepancies would be resolved through re-testing, quality control, or investigation into instrument or reagent issues, rather than human expert adjudication of a "diagnosis."
5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
No, an MRMC comparative effectiveness study was not done. This is an in vitro diagnostic assay, not an AI-powered diagnostic imaging device or an AI assistant for human readers. Its output is a quantitative measurement of cholesterol, not an interpretation that requires human "reading" or decision support.
6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done
Yes, a standalone performance evaluation of the device (Cholesterol2 assay on the ARCHITECT c8000 System) was done. The studies described (reportable interval, precision, lower limits of measurement, linearity, interference, method comparison, tube type, dilution verification) all evaluate the analytical performance of the assay and instrument directly, without human interpretation as part of the primary outcome measure. The output is a numerical concentration of cholesterol.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
The ground truth used for this quantitative assay primarily relies on:
- Reference Methods: Specifically, the Abell-Kendall reference method, which is considered the gold standard for cholesterol measurement and is used in CDC-Certified Cholesterol Reference Method Laboratory Networks (CRMLN). The device's traceability to this method is explicitly stated.
- Analytically Validated Methods: For verifying values in the extended measuring interval.
- Known Spiked Concentrations: For studies such as linearity and dilution verification, where samples are prepared with precisely known concentrations.
This is an analytical ground truth, not a clinical ground truth derived from pathology or patient outcomes.
8. The sample size for the training set
This document does not describe a typical "training set" in the context of machine learning or AI. This is a chemistry assay that uses reagents and enzymatic reactions, not an algorithm that is "trained" on data. Therefore, the concept of a training set as used in AI development is not applicable here. The assay's analytical characteristics are determined through standard laboratory validation studies.
9. How the ground truth for the training set was established
As explained above, there is no "training set" in the AI sense for this device. The analytical accuracy and reliability are established through comparisons to certified reference methods and known standard concentrations, as described in point 7.
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Image /page/0/Picture/0 description: The image shows 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 is in blue and includes the letters "FDA" in a square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION".
June 30, 2022
Abbott Ireland Diagnostics Division Tracy Schmidt Senior Specialist Regulatory Affairs Lisnamuck, Longford Co. Longford, Ireland
Re: K203597
Trade/Device Name: Cholesterol2 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 Dated: March 25, 2022 Received: March 28, 2022
Dear Tracy Schmidt:
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 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.
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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 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/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) 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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). 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 (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely.
Marianela Perez-Torres, Ph.D. Deputy Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K203597
Device Name Cholesterol2
Indications for Use (Describe)
The Cholesterol2 assay is used for the quantitation of cholesterol in human serum or the ARCHITECT c System. The Cholesterol2 assay is to be used an an aid in the diagnosis and treatment of disorders involving excess cholesterol in the blood and lipid 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) |
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510(k) Summary (Summary of Safety and Effectiveness)
This summary of the 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR §807.92.
I. 510(k) Number
II. Applicant Name
Abbott Ireland Diagnostics Division Lisnamuck, Longford, Co. Longford, Ireland
Primary contact person for all communications:
Tracy Schmidt, Sr. Specialist, Regulatory Affairs Abbott Diagnostics Division Phone (224) 668-2833 Fax (224) 668-0194
Secondary contact person for all communications:
Elizabeth Molina Campos, Project Manager, Regulatory Affairs Abbott Diagnostics Division Phone (224) 667-0037 Fax (224) 668-0194
Date Summary Prepared: June 22, 2022.
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III. Device Name
Cholesterol2
Reagents
Trade Name: Cholesterol2 Device Classification: Class I, meets the limitation of exemption per 21 CFR §862.9(c)(4) Classification Name: Enzymatic esterase--oxidase, cholesterol Governing Regulation Number: 21 CFR §862.1175 Product Code: CHH
IV. Predicate Device
Cholesterol (K981652)
V. Description of Device
A. Principles of the Procedure
Cholesterol esters are enzymatically hydrolyzed by cholesterol esterase to cholesterol and free fatty acids. Free cholesterol, including that originally present, is then oxidized by cholesterol oxidase to cholest-4-ene-3-one and hydrogen peroxide. The hydrogen peroxide oxidatively couples with N,N-Bis(4-sulfobutyl)-3-methylaniline (TODB) and 4-aminoantipyrine to form a chromophore (quinoneimine dye) which is quantitated at 604 nm.
Methodology: Enzymatic
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B. Reagents
The configurations of the Cholesterol2 reagent kits are described below.
Volumes (mL) listed in the following table indicate the volume per cartridge.
| List Number | ||
|---|---|---|
| 04S9220 | 04S9230 | |
| Tests per cartridge | 250 | 800 |
| Number of cartridges per kit | 4 | 4 |
| Tests per kit | 1000 | 3200 |
| Reagent 1 (R1) | 21.6 mL | 62.5 mL |
Active ingredients: cholesterol esterase 0.880 KU/L, cholesterol oxidase Reagent 1: (CONII-FD) 0.330 KU/L, TODB 0.466 g/L, 4-aminoantipyrine 0.134 g/L and peroxidase (POD) 6.600 KU/L. Preservative: sodium azide.
The Cholesterol2 reagent is certified to be traceable to the National Reference System for cholesterol, against the Abell-Kendall reference method in a CDC-Certified Cholesterol Reference Method Laboratory Network (CRMLN).
VI. Intended Use of the Device
The Cholesterol2 assay is used for the quantitation of cholesterol in human serum or plasma on the ARCHITECT c System.
The Cholesterol2 assay is to be used as an aid in the diagnosis and treatment of disorders involving excess cholesterol in the blood and lipid and lipoprotein metabolism disorders.
VII. Comparison of Technological Characteristics
The Cholesterol2 assay (subject device) is an automated clinical chemistry assay for the quantitation of cholesterol in human serum or plasma on the ARCHITECT c System.
The similarities and differences between the subject assay and the predicate device are presented in the following table.
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| Characteristics | Subject DeviceCholesterol2 (List No. 04S92) | Predicate DeviceCholesterol (K981652; List No. 7D62) |
|---|---|---|
| Platform | ARCHITECT c8000 System | Same* |
| Intended Use andIndications forUse | The Cholesterol2 assay is used for thequantitation of cholesterol in humanserum or plasma on theARCHITECT c System.The Cholesterol2 assay is to be usedas an aid in the diagnosis andtreatment of disorders involvingexcess cholesterol in the blood andlipid and lipoprotein metabolismdisorders. | The Cholesterol assay is used for thequantitation of cholesterol in humanserum or plasma.Cholesterol measurements are used inthe diagnosis and treatment of disordersinvolving excess cholesterol in theblood and lipid and lipoproteinmetabolism disorders. |
| Methodology | Enzymatic | Same |
| Specimen Type | Human serum or plasma | Same |
| Assay Principle/Principle ofProcedure | Cholesterol esters are enzymaticallyhydrolyzed by cholesterol esterase tocholesterol and free fatty acids. Freecholesterol, including that originallypresent, is then oxidized bycholesterol oxidase to cholest-4-ene-3-one and hydrogen peroxide. Thehydrogen peroxide oxidativelycouples with N,N-Bis(4-sulfobutyl)-3-methylaniline (TODB) and4-aminoantipyrine to form achromophore (quinoneimine dye)which is quantitated at 604 nm. | Cholesterol esters are enzymaticallyhydrolyzed by cholesterol esterase tocholesterol and free fatty acids. Freecholesterol, including that originallypresent, is then oxidized by cholesteroloxidase to cholest-4-ene-3-one andhydrogen peroxide. The hydrogenperoxide combines withhydroxybenzoic acid (HBA) and4-aminoantipyrine to form achromophore (quinoneimine dye) whichis quantitated at 500 nm. |
| Standardization | Human cholesterol (Abell-Kendall) | Same |
| Use of Calibrators | Yes | Same |
| Use of Controls | Yes | Same |
| Assay Range | Analytical Measuring Interval (AMI):5-748 mg/dLExtended Measuring Interval (EMI):748-2992 mg/dLReportable Interval:2-2992 mg/dL | AMI: 7-705 mg/dLEMI: 705-2820 mg/dL |
| Characteristics | Subject DeviceCholesterol2 (List No. 04S92) | Predicate DeviceCholesterol (K981652; List No. 7D62) |
| Platform | ARCHITECT c8000 System | Same* |
| Precision | Samples with cholesterolconcentrations between 21 and718 mg/dL demonstrated standarddeviations ranging from 0.7 to6.9 mg/dL and % Coefficient ofVariation (%CV) values ranging from0.7 to 4.1%. | Samples with cholesterol concentrationsbetween 129.2 and 261.4 mg/dLdemonstrated standard deviationsranging from 2.09 to 4.03 mg/dL and% Coefficient of Variation (%CV)values ranging from 1.5 to 1.6%. |
| Lower Limits ofMeasurement | Limit of Blank: 0 mg/dLLimit of Detection: 2 mg/dLLimit of Quantitation: 5 mg/dL | Limit of Detection: 5.0 mg/dLLimit of Quantitation: 6.2 mg/dL |
| Tube Types | Serum:- Serum tubes- Serum separator tubesPlasma:- Lithium heparin tubes- Lithium heparin separator tubes- Sodium heparin tubes | Serum:Glass or plastic serum tubes with orwithout gel barriersPlasma:Glass or plastic tubes- Lithium heparin tubes (with or withoutgel barrier)- Sodium heparin tubes |
Comparison of Subject Device Cholesterol2 to Predicate Device Cholesterol
In accordance with FDA Guidance Document "Data for Commercialization of Original Equipment Manufacturer, Secondary and Generic Reagent for Automated Analyzers", issued June 10, 1996, the assay equivalency study on ARCHITECT c System vs. the original platform, AEROSET, was performed and submitted under K980367/A004 in May 2002.
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VIII. Summary of Nonclinical Performance
All performance characteristics were obtained using the ARCHITECT c8000 System.
A. Reportable Interval
Based on the limit of detection (LoD), limit of quantitation (LoQ), precision, and linearity, the ranges over which results can be reported are provided below according to the definitions from CLSI EP34, 1st ed.*
| mg/dL | |
|---|---|
| Analytical Measuring Interval (AMI)a | 5–748 |
| Extended Measuring Interval (EMI)b | 748–2992 |
" Clinical and Laboratory Standards Institute (CLS). Establishing and Verifying an Extended Measuring Interval Through Specimen Dilution and Spiking. 1st ed. CLSI Document EP34. Wayne, PA: CLSI; 2018.
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a AMI: The AMI extends from the LoQ to the upper limit of quantitation (ULoQ). This is determined by the range of values in mg/dL that demonstrated acceptable performance for linearity, imprecision, and bias.
b EMI: The EMI extends from the ULoQ to the ULoQ x sample dilution.
C The reportable interval extends from the LoD to the upper limit of the EMI.
NOTE: The default Low Linearity value of the assay file corresponds to the lower limit of the analytical measuring interval. Samples with cholesterol values below 5 mg/dL are reported as "< 5 mg/dL".
B. Within-Laboratory Precision
A study was performed based on guidance from CLSI EP05-A3. Testing was conducted using 3 lots of the Cholesterol2 reagent, 3 lots of the Consolidated Chemistry Calibrator, and 1 lot of commercially available controls and 3 instruments. Two controls and 3 human serum panels were tested in duplicate, twice per day on 20 days on 3 reagent lot/calibrator lot/instrument combinations, where a unique reagent lot and a unique calibrator lot is paired with 1 instrument. The performance from a representative combination is shown in the following table.
| Within-Run(Repeatability) | Within-Laboratorya | |||||
|---|---|---|---|---|---|---|
| Sample | n | Mean(mg/dL) | SD | %CV | SD(Rangeb) | %CV(Rangeb) |
| Control Level 1 | 80 | 251 | 1.9 | 0.7 | 2.6(2.6-3.1) | 1.0(1.0-1.2) |
| Control Level 2 | 80 | 106 | 1.0 | 1.0 | 1.3(1.3-1.7) | 1.2(1.2-1.6) |
| Panel A | 80 | 21 | 0.6 | 3.0 | 0.8(0.7-0.8) | 4.0(3.2-4.1) |
| Panel B | 80 | 237 | 2.8 | 1.2 | 4.5(3.7-4.9) | 1.9(1.5-2.0) |
| Panel C | 80 | 718 | 6.4 | 0.9 | 6.6(4.6-6.9) | 0.9(0.7-1.0) |
ª Includes within-run, between-run, and between-day variability.
b Minimum and maximum SD or %CV across all reagent lot and instrument combinations.
Clinical and Laboratory Standards Institute (CLS). Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline-Third Edition. CLSI Document EP05-A3. Wayne, PA: CLSI; 2014.
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C. Lower Limits of Measurement
A study was performed based on guidance from CLSI EP17-A2. Testing was conducted using 3 lots of the Cholesterol2 reagent on each of 2 instruments over a minimum of 3 days. The maximum observed limit of blank (LoB), limit of detection (LoD), and limit of quantitation (LoQ) values are summarized below.
| mg/dL | |
|---|---|
| LoBa | 0 |
| LoDb | 2 |
| LoQc | 5 |
a The LoB represents the 95th percentile from n ≥ 60 replicates of zero-analyte samples.
b The LoD represents the lowest concentration at which the analyte can be detected with 95% probability based on n ≥ 60 replicates of low-analyte level samples.
6 The LoQ is defined as the lowest concentration at which a maximum allowable precision of 20 %CV was met and was determined from n ≥ 60 replicates of low-analyte level samples.
D. Linearity
A study was performed based on guidance from CLSI EP06-A.*
The assay was demonstrated to be linear across the analytical measuring interval of 5 to 748 mg/dL.
Clinical and Laboratory Standards Institute (CLSI). Evaluation of Detection Capability for Clinical Laboratory Measurent Procedures; Approved Guideline-Second Edition. CLSI Document EP17-A2. Wayne, PA: CLSI; 2012.
* Clinical and Laboratory Standards Institute (CLS). Evaluation of the Linearity of Quanitative Measurement Procedures: A Statistical Approach; Approved Guideline. CLSI Document EP06-A. Wayne, PA: CLSI; 2003.
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E. Potentially Interfering Endogenous and Exogenous Substances
Potentially Interfering Endogenous Substances
A study was performed based on guidance from CLSI EP07, 3rd ed. * Each substance was tested at 2 levels of the analyte (approximately 150 mg/dL and 220 mg/dL). No significant interference (interference within ± 10%, based on 95% confidence intervals) was observed at the following concentrations.
| Potentially Interfering Substance | Interferent Level |
|---|---|
| Conjugated Bilirubin | 7 mg/dL |
| Unconjugated Bilirubin | 11 mg/dL |
| Hemoglobin | 1000 mg/dL |
| Total protein | 15 g/dL |
Interference beyond ± 10% (based on 95% Confidence Intervals [CI]) was observed at the concentrations shown below for the following substance.
| Potentially InterferingSubstance | Interferent Level | Analyte Level | % Interference(95% CI) |
|---|---|---|---|
| Conjugated Bilirubin | 40 mg/dL | 150 mg/dL | -39%(-40%, -39%) |
| Conjugated Bilirubin | 40 mg/dL | 220 mg/dL | -31%(-31%, -30%) |
| Unconjugated Bilirubin | 16 mg/dL | 150 mg/dL | -11%(-11%, -10%) |
Clinical and Laboratory Standards Institute (CLS). Interference Testing in Clinical Chemistry. 3rd ed. CLSI Guideline EP07. Wayne, PA: CLSI; 2018.
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Potentially Interfering Exogenous Substances
No significant interference (interference within ± 10%, based on 95% confidence intervals) was observed at the following concentrations.
| Potentially Interfering Substance | Interferent Level |
|---|---|
| Acetaminophen | 160 mg/L |
| Acetylcysteine | 150 mg/L |
| Acetylsalicylic acid | 30 mg/L |
| Aminoantipyrine | 40 mg/L |
| Ampicillin-Na | 80 mg/L |
| Ascorbic acid | 55 mg/L |
| Biotin | 4250 ng/mL |
| Ca-dobesilate | 60 mg/L |
| Cefotaxime | 53 mg/dL |
| Cefoxitin | 6600 mg/L |
| Cyclosporine | 2 mg/L |
| Desacetylcefotaxime | 6 mg/dL |
| Dipyrone | 100 mg/L |
| Dobutamine | 0.2 mg/dL |
| Doxycycline | 20 mg/L |
| Ibuprofen | 220 mg/L |
| Intralipid | 1050 mg/dL |
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| Potentially Interfering Substance | Interferent Level |
|---|---|
| Levodopa | 8 mg/L |
| Methotrexate | 140 mg/dL |
| Metronidazole | 130 mg/L |
| Methylaminoantipyrine | 40 mg/L |
| Methyldopa | 20 mg/L |
| N-Acetyl-p-benzoquinone (NAPQI) | 20 mg/L |
| Phenylbutazone | 330 mg/L |
| Phenytoin | 6 mg/dL |
| Rifampicin | 50 mg/L |
| Sodium heparin | 4 U/mL |
| Sulpiride | 15 mg/L |
| Theophylline (1,3-dimethylxanthine) | 60 mg/L |
Interference beyond ± 10% (based on 95% Confidence Intervals [CI]) was observed at the concentrations below for the following substance.
| Potentially InterferingSubstance | Interferent Level | Analyte Level | % Interference(95% CI) |
|---|---|---|---|
| Ascorbic acid | 60 mg/L | 150 mg/dL | -10%(-11%, -10%) |
| Intralipid | 2000 mg/dL | 150 mg/dL | -27%(-27%, -28%) |
| Intralipid | 2000 mg/dL | 220 mg/dL | -22%(-21%, -23%) |
| Methyldopa | 30 mg/L | 150 mg/dL | -14%(-14%, -13%) |
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F. Method Comparison
A study was performed based on guidance from CLSI EP09-A3* using the Passing-Bablok regression method. The study compared the Cholesterol2 assay to the Cholesterol assay (List Number 7D62).
| Cholesterol2 vs. Cholesterol on the ARCHITECT c8000 System | ||||||
|---|---|---|---|---|---|---|
| Units | n | CorrelationCoefficient | Intercept | Slope | ConcentrationRange | |
| Serum | mg/dL | 138 | 1.00 | 0.41 | 0.98 | 7-684 |
G. Tube Type
A study was performed to evaluate the suitability of specific blood collection tube types for use with the Cholesterol2 assay. Samples were collected from a minimum of 40 donors and evaluated across tube types. The following blood collection tube types were determined to be acceptable for use with the Cholestero12 assay:
Serum tubes Serum separator tubes Lithium heparin tubes Lithium heparin separator tubes Sodium heparin tubes
Clinical and Laboratory Standards Institute (CLS). Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guideline-Third Edition. CLSI Document EP09-A3. Wayne, PA: CLSI; 2013.
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H. Dilution Verification
A study was performed to evaluate the performance of the Cholesterol2 automated dilution protocol and the manual dilution procedure on the ARCHITECT c8000 System.
Eight human serum samples were created by spiking cholesterol stock solution into SeraSub (a synthetic serum) to target concentrations across the extended measuring interval (EMI) (805, 1000, 1250, 1500, 1800, 2000, 2500, and 2800 mg/dL) that were value assigned using the analytically validated method.
The automated dilution factor for the Cholestero12 assay is 1:5.97.
The manual dilution factor of 1:4 was evaluated for the Cholesterol2 assay.
I. Certificate of Traceability
The Cholesterol2 reagent is certified to be traceable to the National Reference System for Cholesterol, against the Abell-Kendall reference method in a CDC-Certified Cholesterol Reference Method Laboratory Network (CRMLN).
IX. Summary of Clinical Performance
This section does not apply.
X. Conclusion Drawn from Nonclinical Laboratory Studies
The results presented in this 510(k) premarket notification demonstrate that the performance of the subject device. Cholesterol2 (List No. 04S92), is substantially equivalent to the predicate device, Cholesterol (List No. 7D62, K981652).
The similarities and differences between the subject device and predicate device are presented in Section 5-VII.
There is no known potential adverse effect to the operator when using this in vitro device according to the Cholesterol2 reagent package insert instructions.
§ 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.