VITROS XT Chemistry Products TRIG-CHOL Slides
Device Facts
| Record ID | K190490 |
|---|---|
| Device Name | VITROS XT Chemistry Products TRIG-CHOL Slides |
| Applicant | Ortho-Clinical Diagnostics, Inc. |
| Product Code | CHH · Clinical Chemistry |
| Decision Date | Mar 27, 2019 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.1175 |
| Device Class | Class 1 |
Intended Use
The TRIG test within the VITROS XT Chemistry Products TRIG-CHOL Slides quantitatively measure triglyceride (TRIG) concentration in serum and plasma using VITROS XT 7600 Integrated Systems. Triglyceride measurements are used in the diagnosis and treatment of patients with diabetes mellitus, nephrosis, liver obstruction, other diseases involving lipid metabolism, or various endocrine disorders. The CHOL test within the VITROS XT Chemistry Products TRIG-CHOL Slides quantitatively measure cholesterol (CHOL) concentration in serum and plasma using VITROS XT 7600 Integrated Systems. Lipoprotein measurements are used in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis, and various liver and renal diseases.
Device Story
VITROS XT Chemistry Products TRIG-CHOL Slides are multilayered analytical elements on polyester support; contain both TRIG and CHOL tests in a single slide frame. Input: patient serum or plasma sample. Operation: sample deposited on slide; spreading layer distributes sample; Triton X-100 dissociates lipoprotein complexes. TRIG test: lipase hydrolyzes triglycerides to glycerol; glycerol kinase/oxidase/peroxidase reactions produce dye. CHOL test: cholesterol ester hydrolase/oxidase/peroxidase reactions produce dye. Output: dye density measured via reflectance spectrophotometry on VITROS XT 7600 Integrated Systems. Used in clinical laboratories by technicians. Output provides quantitative analyte concentration; aids clinicians in diagnosing/treating lipid-related metabolic and cardiovascular conditions.
Clinical Evidence
Bench testing only. Method comparison (N=148) against predicate devices showed high correlation (r=1.000 for TRIG, r=0.999 for CHOL). Precision evaluated over 20 days (80 observations) with CV% ranging 0.3-1.5% for TRIG and 0.6-2.1% for CHOL. Linearity verified across claimed ranges. Interference testing performed per CLSI EP07-03.
Technological Characteristics
Multilayered analytical elements on polyester support; plastic barrier separates TRIG and CHOL tests. Principle: reflectance spectrophotometry of colorimetric enzymatic reactions. Reagents: lipase, peroxidase, glycerol kinase, cholesterol oxidase, cholesterol ester hydrolase, Triton X-100, leuco dye. Dimensions: single slide frame. Connectivity: integrated with VITROS XT 7600 system. Sterilization: not specified.
Indications for Use
Indicated for in vitro diagnostic use in patients requiring quantitative measurement of triglyceride and cholesterol concentrations in serum and plasma to assist in the diagnosis and treatment of diabetes mellitus, nephrosis, liver diseases, lipid metabolism disorders, endocrine disorders, atherosclerosis, and renal diseases.
Regulatory Classification
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.
Related Devices
- K130332 — VITROS CHEMISTRY PRODUCTS TRIG SLIDES · Ortho-Clinical Diagnostics, Inc. · May 31, 2013
Submission Summary (Full Text)
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March 27, 2019
Ortho-Clinical Diagnostics, Inc. Alexandra Chamberlain Senior Regulatory Associate, Regulatory Affairs 100 Indigo Creek Drive Rochester, NY 14626
Re: K190490
Trade/Device Name: VITROS XT Chemistry Products TRIG-CHOL Slides Regulation Number: 21 CFR 862.1175 Regulation Name: Cholesterol (total) test system Regulatory Class: Class I, meets the limitation to the exemption 21 CFR 862.9 (c)(4) Product Code: CHH, CDT Dated: February 27, 2019 Received: February 28, 2019
Dear Alexandra Chamberlain:
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.
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
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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 post marketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, vou may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely.
# Kellie B. Kelm -S
for Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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#### Indications for Use
510(k) Number (if known) K190490
Device Name VITROS XT Chemistry Products TRIG-CHOL Slides
Indications for Use (Describe) Rx Only For in vitro diagnostic use only
The TRIG test within the VITROS XT Chemistry Products TRIG-CHOL Slides quantitatively measure triglyceride (TRIG) concentration in serum and plasma using VITROS XT 7600 Integrated Systems. Triglyceride measurements are used in the diagnosis and treatment of patients with diabetes mellitus, nephrosis, liver diseases involving lipid metabolism, or various endocrine disorders.
The CHOL test within the VITROS XT Chemistry Products TRIG-CHOL Slides quantitatively measure cholesterol (CHOL) concentration in serum and plasma using VITROS XT 7600 Integrated Systems. Lipoprotein measurements are used in the diagnosis and treatment of lipid disorders mellitus), atherosclerosis, and various liver and renal diseases.
Type of Use (Select one or both, as applicable)
| <input checked="true" type="checkbox"/> Prescription Use (Part 21 CFR 801 Subpart D) |
|--------------------------------------------------------------------------------------|
| <input type="checkbox"/> Over-The-Counter Use (21 CFR 801 Subpart C) |
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# 5. 510(k) Summary
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92. The assigned 510(k) number is: K190490
#### Submitter's Information
Ortho-Clinical Diagnostics, Inc. 100 Indigo Creek Drive Rochester, New York 14626-5101 Phone: (585) 453-3475 Fax: (585) 453-3368
#### Contact Person
Alexandra Chamberlain, RAC Senior Regulatory Associate, Regulatory Affairs
Date of Preparation March 22, 2019
#### Device Proprietary Name(s)
VITROS XT Chemistry Products TRIG-CHOL Slides
#### Common Names
Triglyceride assay Cholesterol assay
#### Classification Names
| VITROS | Product Code | Class | Regulation Section | Panel |
|--------|--------------|----------|----------------------------------------------------|-----------------------|
| TRIG | CDT | Class I* | 21 CFR 862.1705 Triglyceride test<br>system | Clinical<br>Chemistry |
| CHOL | CHH | Class I* | 21 CFR 862.1175 Cholesterol<br>(total) test system | (75) |
*Meet the limitations of exemptions per 21 CFR 862.9(c) (4) and will require a premarket notification because both analytes are used in assessing the risk of cardiovascular diseases.
#### Predicate Device(s)
| Predicate Devices | FDA 510(k) Number |
|---------------------------------------|-------------------|
| VITROS Chemistry Products TRIG Slides | K130332 |
| VITROS Chemistry Products CHOL Slides | K820263 |
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## Intended Use Statement(s) VITROS XT Chemistry Products TRIG-CHOL Slides Rx Only
For in vitro diagnostic use only
The TRIG test within the VITROS XT Chemistry Products TRIG-CHOL Slides quantitatively measure triglyceride (TRIG) concentration in serum and plasma using VITROS XT 7600 Integrated Systems. Triglyceride measurements are used in the diagnosis and treatment of patients with diabetes mellitus, nephrosis, liver obstruction, other diseases involving lipid metabolism, or various endocrine disorders.
The CHOL test within the VITROS XT Chemistry Products TRIG-CHOL Slides quantitatively measure cholesterol (CHOL) concentration in serum and plasma using VITROS XT 7600 Integrated Systems. Lipoprotein measurements are used in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis, and various liver and renal diseases.
#### Device Description
The new device, the VITROS XT Chemistry Products TRIG-CHOL Slide is a single device that contains both a TRIG test and a CHOL test multilayered, analytical elements coated on a polyester support separated by a plastic barrier sealed within a single slide frame. In this format, individual reactions occur and test results are generated for each analyte independently of the other analyte.
To perform the TRIG test, a drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlying layers. The Triton X-100 surfactant in the spreading layer aids in dissociating the triglycerides from lipoprotein complexes present in the sample. The triglyceride molecules are then hydrolyzed by lipase to yield glycerol and fatty acids. Glycerol diffuses to the reagent layer, where it is phosphorylated by glycerol kinase in the presence of adenosine triphosphate (ATP). In the presence of L-a-glycerolphosphate oxidase, L-α-glycerophosphate is then oxidized to dihydrox vacetone phosphate and hydrogen peroxide. The final reaction involves the oxidation of a leuco dye by hydrogen peroxide, catalyzed by peroxidase, to produce a dye. The density of the dye formed is proportional to the triglyceride concentration present in the sample and is measured by reflectance spectrophotometry.
To perform the CHOL test, a drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlying layers. The Triton X-100 (TX100) surfactant in the spreading layer aids in dissociating the cholesterol and cholesterol esters from lipoprotein complexes present in the sample. Hydrolysis of the cholesterol esters to cholesterol is catalyzed by cholesterol ester hydrolase. Free cholesterol is then oxidized in the presence of cholesterol oxidase to form cholestenone and hydrogen peroxide. Finally, hydrogen peroxide oxidizes a leuco dye in the presence of peroxidase to generate a colored dye. The density of dye formed is proportional to the cholesterol concentration present in the sample and is measured by reflectance spectrophotometry.
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## Comparison to Predicate Devices
The following tables show similarities and differences between the new and predicate devices.
| Summary of the technological characteristics of the device compared to the predicate device | | |
|---------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Device Characteristic | New Device<br>VITROS XT TRIG-CHOL Slide<br>(New) | Predicate Devices<br>VITROS TRIG Slide [K130332]<br>VITROS CHOL Slide [K820263]<br>(Current) |
| Intended Use | Same for each individual test<br>For in vitro diagnostic use only. | For in vitro diagnostic use only. |
| | The TRIG test within the VITROS<br>XT Chemistry Products TRIG-<br>CHOL Slides quantitatively measure<br>triglyceride (TRIG)<br>concentration in serum and plasma. | VITROS Chemistry Products<br>TRIG Slides quantitatively<br>measure triglyceride (TRIG)<br>concentration in serum and<br>plasma. |
| | The CHOL test within the VITROS<br>XT Chemistry Products TRIG-<br>CHOL Slides quantitatively measure<br>cholesterol (CHOL)<br>concentration in serum and plasma. | VITROS Chemistry Products<br>CHOL Slides quantitatively<br>measure cholesterol (CHOL)<br>concentration in serum and<br>plasma. |
| Device Description | No Change | Multilayered, analytical element<br>coated on a polyester support |
| Basic Principle | No Change | TRIG Colorimetric<br>CHOL Colorimetric |
| Incubation time and<br>temperature | No Change | Approximately 5 minutes<br>37°C (98.6° F) |
| Sample type | No Change | Serum and plasma |
| Amount of Slide<br>Reactive Ingredients<br>per slide (test) | The composition of the analytical<br>element of each test within the<br>VITROS XT Slide will remain the<br>same as that used in each predicate<br>devices | TRIG<br>Lipase ( <i>Pseudomonas</i> sp.) 0.08 U;<br>peroxidase (horseradish root) 0.52<br>U; glycerol kinase ( <i>Cellulomonas</i><br>sp.) 0.35 U; L-a-glycerophosphate<br>oxidase ( <i>Pediococcus</i> sp.) 0.19 U;<br>Triton X-100 0.62 mg; 2-(3,5-<br>dimethoxy-4-hydroxyphenyl)-4,5-<br>bis(4-dimethylaminophenyl)<br>imidazole (leuco dye) 0.04 mg;<br>and adenosine triphosphate 0.14<br>mg. |
| Summary of the technological characteristics of the device compared to the predicate device | | |
| Device Characteristic | New Device<br>VITROS XT TRIG-CHOL Slide<br>(New) | Predicate Devices<br>VITROS TRIG Slide [K130332]<br>VITROS CHOL Slide [K820263]<br>(Current) |
| | | CHOL<br>Triton X-100 0.81 mg; cholesterol<br>oxidase ( <i>Cellulomonas</i> sp.) 0.4 U;<br>cholesterol ester hydrolase<br>( <i>Pseudomonas</i> sp.) 2.0 U;<br>peroxidase (horseradish root) 5.3<br>U; and 2-(3,5-dimethoxy- 4-<br>hydroxyphenyl)-4,5-bis-(4-<br>dimethylaminophenyl) imidazole<br>(leuco dye) 0.17 mg. |
| Assay Range | No Change | TRIG 10.0-525.0 mg/dL<br>CHOL 50-325 mg/dL |
| Calibrators | Same | VITROS Chemistry Products<br>Calibrator Kit 2 |
| Controls | Same | VITROS Chemistry Products<br>Performance Verifier I and II |
| Differences | | |
| Instrumentation | VITROS XT 7600 Integrated System | VITROS 250/350, 5,1 FS and<br>4600 Chemistry Systems<br>VITROS 5600 and XT 7600<br>Integrated Systems |
| Sample volume | TRIG 2.9 µL<br>CHOL 3.9 µL | TRIG 5.5 µL<br>CHOL 5.5 µL |
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#### Non-Clinical Testing Analytical Performance
#### Method Comparison
Method Comparison testing followed CLSI Protocol EP09c, Measurement Procedure Comparison and Bias Estimation Using Patient Samples, Serum samples were evaluated on the VITROS XT Chemistry Products TRIG-CHOL Slides using the VITROS XT 7600 Integrated System and on VITROS Chemistry Products TRIG Slides and VITROS Chemistry Products CHOL Slides using the VITROS 5600 Integrated System. The correlation between the predicate and the new tests within the VITROS XT TRIG-CHOL Slides on the VITROS XT 7600 Integrated System is summarized below.
Summary of Method Comparison Weighted Deming Regression Analysis Data Units mg/dL
| Test | N | Slope | Intercept | Corr.<br>Coeff. | Test Range | Measuring<br>range |
|------------|-----|-------|-----------|-----------------|------------|--------------------|
| TRIG Serum | 148 | 0.99 | 1.49 | 1.000 | 17 - 519 | 10 - 525 |
| CHOL Serum | 148 | 0.97 | 0.09 | 0.999 | 72 - 315 | 50 - 325 |
## Precision
Precision was evaluated with patient pools and quality control materials following CLSI Protocol EP05-A3, Evaluation of Precision Performance of Quantitative Methods; Approved Guideline-Third Edition, using the VITROS XT Chemistry Products TRIG-CHOL Slides on the VITROS XT 7600 Integrated System. The test included 80 observations (2 replicates per run, 2 runs per day over 20 days) for serum. The long term precision analysis is summarized below.
The data presented are a representation of test performance and are provided as a guideline. Variables such as sample handling and storage, reagent handling and storage, laboratory environment, and system maintenance can affect reproducibility of test results.
| TRIG Serum Units (mg/dL) | | | | | | | | | |
|--------------------------|-------|---------------|-----|------------|-----|------------|-----|--------|--------|
| | Mean | Repeatability | | Within Day | | Within Lab | | No. of | No. of |
| Fluid Id | Conc. | SD | CV% | SD | CV% | SD | CV% | Obs. | Days |
| Pool 1 | 29 | 0.2 | 0.6 | 0.3 | 1.0 | 0.4 | 1.3 | 80 | 20 |
| Native Pool | 90 | 0.3 | 0.3 | 0.9 | 1.0 | 1.4 | 1.5 | 80 | 20 |
| Control 1 | 115 | 0.4 | 0.3 | 0.6 | 0.5 | 0.8 | 0.7 | 80 | 20 |
| Control 2 | 255 | 1.1 | 0.4 | 1.5 | 0.6 | 2.1 | 0.8 | 80 | 20 |
| Pool 2 | 379 | 1.4 | 0.4 | 2.3 | 0.6 | 3.4 | 0.9 | 80 | 20 |
| Pool 3 | 513 | 1.7 | 0.3 | 3.1 | 0.6 | 4.5 | 0.9 | 80 | 20 |
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| CHOL Serum Units (mg/dL) | | | | | | | | | |
|--------------------------|-------|---------------|-----|------------|-----|------------|-----|--------|--------|
| | Mean | Repeatability | | Within Day | | Within Lab | | No. of | No. of |
| Fluid Id | Conc. | SD | CV% | SD | CV% | SD | CV% | Obs. | Days |
| Pool 1 | 74 | 0.6 | 0.8 | 0.6 | 0.8 | 1.6 | 2.1 | 80 | 20 |
| Control 1 | 149 | 1.5 | 1.0 | 1.5 | 1.0 | 2.9 | 1.9 | 80 | 20 |
| Native Pool | 159 | 1.2 | 0.8 | 1.4 | 0.9 | 2.1 | 1.3 | 80 | 20 |
| Pool 2 | 208 | 1.5 | 0.7 | 2.1 | 1.0 | 3.1 | 1.5 | 80 | 20 |
| Control 2 | 261 | 1.5 | 0.6 | 2.5 | 1.0 | 4.2 | 1.6 | 80 | 20 |
| Pool 3 | 312 | 2.1 | 0.7 | 3.3 | 1.1 | 4.7 | 1.5 | 80 | 20 |
## Detection Capability
Detection capability studies for the TRIG and CHOL tests within the VITROS XT TRIG-CHOL Slides were evaluated according to CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures.
The Limit of Quantitation (LoQ) for the TRIG test within the VITROS XT TRIG-CHOL Slides is 10 mg/dL. The total number of LoQ determinations was 180. The criteria used to accept the LoQ was %CV < 20%.
The Limit of Quantitation (LoQ) for the CHOL test within the VITROS XT TRIG-CHOL Slides is 50 mg/dL. The total number of LoQ determinations was 180. The criteria used to accept the LoQ was %CV < 9%.
| | TRIG (mg/dL) | CHOL (mg/dL) |
|-------------|--------------|--------------|
| | Serum | Serum |
| LOB | 3.8 | 1.8 |
| LOD | 4.1 | 2.1 |
| LOQ | 6.5 | 17.6 |
| Claimed LOQ | 10 | 50 |
The results of this analysis are summarized below:
## Linearity
Linearity studies were performed according to CLSI EP06-A, Evaluation of the Linearity of Ouantitative Measurement Procedures: A Statistical Approved Guideline (2003). VITROS XT TRIG-CHOL Slides were tested on the VITROS XT 7600 Integrated System. A series of eighteen proportionally related admixtures of low and high test fluids were tested to verify linearity of the TRIG and CHOL serum tests; each sample was tested in quadruplicate. The linearity studies support the claimed measuring ranges for the individual tests within the VITROS XT TRIG-CHOL Slides.
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| Assay | Fluid | Measuring Range<br>(mg/dL) | Linear Range<br>(mg/dL) | Claimed Linearity<br>(mg/dL) |
|-------|--------------|----------------------------|-------------------------|------------------------------|
| TRIG | Serum/plasma | 10 - 525 | 8.0 - 542.8 | 10 - 525 |
| CHOL | Serum/plasma | 50 - 325 | 27 - 358 | 50 - 325 |
Serum and plasma samples with values greater than the measuring range should be diluted with 1 part sample with 2 parts diluent for the TRIG test and with1 part sample with 1 part diluent for the CHOL test. A 7% BSA solution was found to be an acceptable diluent for serum and plasma specimens assayed using VITROS XT Chemistry Products TRIG-CHOL Slides.
## Expected Values
The National Cholesterol Education Program (NCEP) sets the guidelines for TRIG and CHOL and uses a classification scheme in place of a reference interval for the expected values. The expected values of the TRIG and CHOL tests within the VITROS XT TRIG-CHOL Slides are the not changed from those of the predicate assays.
Each laboratory should confirm the validity of these intervals for the population it serves.
#### TRIG Classification
Triglyceride levels are categorized according to the classification scheme in the ATP III guidelines recommended by NCEP for samples collected from fasting patients.
| Classification | Conventional Units<br>(mg/dL) | SI Units (mmol/L) | Alternate Units<br>(g/L) |
|-----------------|-------------------------------|-------------------|--------------------------|
| Normal | < 150 | < 1.69 | < 1.50 |
| Borderline High | 150—199 | 1.69–2.25 | 1.50-1.99 |
| High | 200—499 | 2.26-5.64 | 2.00-4.99 |
| Very High | ≥ 500 | ≥ 5.65 | ≥ 5.00 |
#### CHOL Classification
Cholesterol levels are categorized according to the classification scheme in the ATP III guidelines recommended by NCEP for samples collected from fasting patients.
| Classification | Conventional Units<br>(mg/dL) | SI Units (mmol/L) | Alternate Units<br>(g/L) |
|-----------------|-------------------------------|-------------------|--------------------------|
| Desirable | < 200 | < 5.2 | < 2.0 |
| Borderline High | 200–239 | 5.2-6.2 | 2.0-2.4 |
| High | ≥ 240 | ≥ 6.2 | ≥ 2.4 |
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## Specificity
The TRIG and CHOL tests within the VITROS XT Chemistry Products TRIG-CHOL Slide were screened for interfering substances following CLSI EP07-03, Interference Testing in Clinical Chemistry. The supplemental tables in CLSI document EP37 were referenced for recommended testing concentrations for analytes and endogenous substances that may interfere in clinical chemistry measurement procedures.
Point estimates of the effects of potential interferents on VITROS XT TRIG-CHOL Slides were made using the paired difference method. Dose-response analysis was conducted to characterize the degree of interference for each substance, and expected bias was reported at the lowest test level which did not meet acceptance criteria for bias as shown in the product claims.
#### Serum
#### Known Interferences
Free glycerol in serum is measured along with the glycerol from the hydrolysis of triglycerides and diglycerides. Certain clinical conditions show high endogenous free glycerol levels.2 Some drugs are also known to produce elevated glycerol levels in serum. Triglyceride results from samples of such patients will not reflect actual serum triglyceride content.
Grossly lipemic samples show a slower rate of color development than do clear serums, which results in a negative bias. These samples often contain triglyceride concentrations greater than the system's measuring (reportable or dynamic) range. Grossly lipemic samples should be diluted prior to testing.
The substances listed in the table, when tested at the concentrations indicated, caused the bias shown. The bias is an estimate of the maximum bias observed.
It is possible that other interfering substances may be encountered. These results are representative; however, your results may differ somewhat due to test-to-test variation. The degree of interference at concentrations other than those listed might not be predictable.
#### TRIG Test
For the TRIG test within VITROS XT TRIG-CHOL Slides, interference was observed for two (2) substances.
| Interferent | Interferent<br>Concentration | Triglycerides<br>Concentration | Bias |
|---------------|------------------------------|--------------------------------|------------|
| Dextran 40 | 2 g/dL | 140 mg/dL | 29.6 mg/dL |
| Dextran 40 | 2 g/dL | 504 mg/dL | 62.7 mg/dL |
| Total protein | 12 g/dL | 138 mg/dL | 19.0 mg/dL |
| | 15 g/dL | 496 mg/dL | 62.9 mg/dL |
For the TRIG test within VITROS XT TRIG-CHOL Slides, no interference was observed for seventy-eight (78) substances when tested at the concentrations listed.
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## CHOL Test
For the CHOL test within VITROS XT TRIG-CHOL Slides, interference was observed for seven (7) substances.
| Interferent | Interferent<br>Concentration | Cholesterol<br>Concentration | Bias |
|------------------|------------------------------|------------------------------|------------|
| Ascorbic acid | 5.2 mg/dL | 145 mg/dL | -14 mg/dL |
| Ascorbic acid | 30.1 mg/dL | 249 mg/dL | -101 mg/dL |
| Cefazolin | 120 mg/dL | 153 mg/dL | -18 mg/dL |
| Cefazolin | 120 mg/dL | 249 mg/dL | -29 mg/dL |
| Dextran 40 | 4 g/dL | 157 mg/dL | -24 mg/dL |
| Dextran 40 | 4 g/dL | 265 mg/dL | -49 mg/dL |
| Glutathione | 69 mg/dL | 147 mg/dL | -21 mg/dL |
| Hemoglobin | 1000 mg/dL | 166 mg/dL | -17 mg/dL |
| N-Acetylcysteine | 15 mg/dL | 147 mg/dL | -20 mg/dL |
| N-Acetylcysteine | 42 mg/dL | 246 mg/dL | -69 mg/dL |
| Total protein | 10 g/dL | 154 mg/dL | 20 mg/dL |
| Total protein | 12 g/dL | 263 mg/dL | 42 mg/dL |
For the CHOL test within VITROS XT TRIG-CHOL Slides, no interference was observed for seventy-nine (79) substances when tested at the concentrations listed.
#### Other Limitations
Certain drugs and clinical conditions are known to alter triglyceride and cholesterol concentrations in vivo. For additional information, refer to one of the published summaries.
#### Conclusion
The conclusions drawn from the nonclinical tests (discussed above) demonstrate the VITROS XT Chemistry Products TRIG-CHOL Slides for use on the VITROS XT 7600 Integrated System are as safe, effective, and perform as well as the predicate devices. The information submitted in the premarket notification is complete and supports a substantial equivalence decision.
#### References
- 1. NCEP. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III), Final Report. NIH Publication No. 02-5215. National Institutes of Health. Bethesda, Maryland: September 2002.
- 2. Stein EA, et al. National Cholesterol Education Program Recommendations for Triglyceride Measurement: Executive Summary. Clin. Chem. 41:1421-1426; 1995.
