VITROS XT Chemistry Products GLU-Ca Slides

K190520 · Ortho-Clinical Diagnostics, Inc. · CGA · Apr 3, 2019 · Clinical Chemistry

Device Facts

• Record ID: K190520
• Device Name: VITROS XT Chemistry Products GLU-Ca Slides
• Applicant: Ortho-Clinical Diagnostics, Inc.
• Product Code: CGA · Clinical Chemistry
• Decision Date: Apr 3, 2019
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1345
• Device Class: Class 2
• Attributes: Pediatric

Intended Use

The GLU test within the VITROS XT Chemistry Products GLU-Ca Slides quantitatively measures glucose (GLU) concentration in serum, plasma, urine, and cerebrospinal fluid using VITROS XT 7600 Integrated Systems. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, and idiopathic hypoglycemia, and of pancreatic islet cell carcinoma. The Ca test within the VITROS XT Chemistry Products GLU-Ca Slides quantitatively measures calcium (Ca) concentration in serum, plasma, and urine using VITROS XT 7600 Integrated Systems. Calcium measurements are used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany (intermittent muscular contractions or spasms).

Device Story

VITROS XT Chemistry Products GLU-Ca Slides are single-use analytical elements containing both GLU and Ca test patches separated by a plastic barrier. Used on VITROS XT 7600 Integrated Systems in clinical laboratory settings. For glucose: sample oxidation catalyzed by glucose oxidase produces hydrogen peroxide, leading to oxidative coupling and dye formation; intensity measured by reflected light. For calcium: sample dissociates from binding proteins, complexes with Arsenazo III dye, causing absorption shift; reflection density measured spectrophotometrically. Results generated independently for each analyte. Healthcare providers use quantitative results to diagnose and monitor metabolic, endocrine, and bone-related conditions. Benefits include consolidated testing on a single slide, reducing sample volume requirements and improving laboratory workflow efficiency.

Clinical Evidence

Bench testing only. Method comparison followed CLSI EP09c using patient samples (serum, urine, CSF) comparing VITROS XT 7600 to predicate systems. Correlation coefficients were 1.000 for GLU and 0.999 for Ca. Precision evaluated per CLSI EP05-A3 (80 observations over 20 days); results showed high reproducibility. Linearity verified per CLSI EP06-A. Interference testing performed per CLSI EP07/EP37; specific biases identified for substances like glutathione, hemoglobin, and ascorbic acid. No clinical trials were required.

Technological Characteristics

Multilayered analytical elements on polyester support. GLU assay: glucose oxidase/peroxidase colorimetric. Ca assay: Arsenazo III dye complexometric. Dimensions: single slide frame. Connectivity: integrated with VITROS XT 7600 system. Energy source: optical/spectrophotometric measurement. Sterilization: not specified. Software: embedded system control.

Indications for Use

Indicated for quantitative measurement of glucose in serum, plasma, urine, and CSF, and calcium in serum, plasma, and urine. Used for diagnosis/treatment of carbohydrate metabolism disorders (diabetes, neonatal/idiopathic hypoglycemia), pancreatic islet cell carcinoma, parathyroid disease, bone diseases, chronic renal disease, and tetany. Prescription use only.

Regulatory Classification

Identification

A glucose test system is a device intended to measure glucose quantitatively in blood and other body fluids. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, and idiopathic hypoglycemia, and of pancreatic islet cell carcinoma.

Special Controls

*Classification.* Class II (special controls). The device, when it is solely intended for use as a drink to test glucose tolerance, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.

Submission Summary (Full Text)

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Image /page/0/Picture/0 description: The image contains 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 agency's name, "U.S. Food & Drug Administration."

April 3, 2019

Ortho-Clinical Diagnostics, Inc. Darlene Phillips Manager, Regulatory Affairs 100 Indigo Creek Drive Rochester, NY 14626

Re: K190520

Trade/Device Name: VITROS XT Chemistry Products GLU-Ca Slides Regulation Number: 21 CFR 862.1345 Regulation Name: Glucose test system Regulatory Class: Class II Product Code: CGA, CJY Dated: February 28, 2019 Received: March 4, 2019

Dear Darlene Phillips:

We have reviewed vour 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 Mav 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/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; 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 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, you 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 ([e-mail]) or phone [phone] 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) k190520

Device Name VITROS XT Chemistry Products GLU-Ca Slides

#### Indications for Use (Describe)

For in vitro diagnostic use only

The GLU test within the VITROS XT Chemistry Products GLU-Ca Slides quantitatively measures glucose (GLU) concentration in serum, plasma, urine, and cerebrospinal fluid using VITROS XT 7600 Integrated Systems. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders mellitus. neonatal hypoglycemia, and idiopathic hypoglycemia, and of pancreatic islet cell carcinoma.

The Ca test within the VITROS XT Chemistry Products GLU-Ca Slides quantitatively measures calcium (Ca) concentration in serum, plasma, and urine using VITROS XT 7600 Integrated Systems. Calcium measurements are used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany (intermittent muscular contractions or spasms).

Special conditions for use statement: For prescription use only.

Type of Use (Select one or both, as applicable)|X Prescription Use (Part 21 CFR 801 Subpart D)

| | Over-The-Counter Use (21 CFR 801 Subpart C)

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### 510(k) Summary

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92. The assigned 510(k) number is: k190520

#### Submitter's Information

Ortho-Clinical Diagnostics, Inc. 100 Indigo Creek Drive Rochester, New York 14626-5101 Phone: [phone] Fax: [phone]

#### Contact Person:

Darlene J Phillips, RAC Manager, Regulatory Affairs

Date of Preparation: February 28, 2019

#### Device Proprietary Name(s):

VITROS XT Chemistry Products GLU-Ca Slides

#### Common Names:

Glucose test Calcium test

#### Classification Names

| Test | Product<br>Code | Class | Regulation Section | Panel |
|------|-----------------|----------|--------------------------------------|---------------|
| GLU | CGA | Class II | 21 CFR 862. 1345 Glucose test system | Clinical |
| Ca | CJY | Class II | 21 CFR 862. 1145 Calcium test system | Chemistry(75) |

#### Predicate Device(s)

| Predicate Devices | FDA 510(k) Number |
|--------------------------------------|-------------------|
| VITROS Chemistry Products GLU Slides | k182072 |
| VITROS Chemistry Products Ca Slides | k072440 |

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### Intended Use Statement(s) VITROS XT Chemistry Products GLU-Ca Slides

Rx Only. For in vitro diagnostic use only.

The GLU test within the VITROS XT Chemistry Products GLU-Ca Slides quantitatively measures glucose (GLU) concentration in serum, plasma, urine, and cerebrospinal fluid using VITROS XT 7600 Integrated Systems. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, and idiopathic hypoglycemia, and of pancreatic islet cell carcinoma.

The Ca test within the VITROS XT Chemistry Products GLU-Ca Slides quantitatively measures calcium (Ca) concentration in serum. plasma, and urine using VITROS XT 7600 Integrated Systems. Calcium measurements are used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany (intermittent muscular contractions or spasms).

#### Device Description

The new device, the VITROS XT Chemistry Products GLU-Ca Slides is a single device that contains both a GLU test and a Ca test side by side 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.

For glucose measurement, a drop of patient sample is deposited on the GLU test element of the slide and is evenly distributed by the spreading layer to the underlying layers. The oxidation of sample glucose is catalyzed by glucose oxidase to form hydrogen peroxide and gluconate. This reaction is followed by an oxidative coupling catalyzed by peroxidase in the presence of dye precursors to produce a dye. The intensity of the dye is measured by reflected light. The dye system used is closely related to that first reported by Trinder. ' The chemistry of the glucose slides has been described by Curme, et al.

For calcium measurement, a drop of patient sample is deposited on the Ca test element of the slide and is evenly distributed by the spreading layer to the underlying layers. The bound calcium is dissociated from binding proteins, allowing the calcium to penetrate through the spreading layer into the underlying reagent layer. There, the calcium forms a complex with Arsenazo III dye, causing a shift in the absorption maximum. After incubation, the reflection density of the colored complex is measured spectrophotometrically. The amount of colored complex formed is proportional to the calcium concentration in the sample.

Trinder P. Determination of Glucose in Blood Using Glucose Oxidase with an l Alternative Oxygen Receptor. Ann. Clin. Biochem. 6:24; 1969.

Curme HG. et al. Multilayer Film Elements for Clinical Analysis. Clin. Chem. 2. 24:1335—1342; 1978.

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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<br>predicate device | | |
|------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Device<br>Characteristic | New Device<br>VITROS XT GLU-Ca Slide<br>(New) | Predícate Devices<br>VITROS GLU Slide [k182072]<br>VITROS Ca Slide [k072440]<br>(Current) |
| Intended Use | Same for each individual test<br><br>For <i>in vitro</i> diagnostic use only.<br>The GLU test within the VITROS<br>XT Chemistry Products GLU-<br>Ca Slides quantitatively<br>measures glucose (GLU)<br>concentration in serum, plasma,<br>urine, and cerebrospinal fluid<br>(CSF).<br><br>The Ca test within the VITROS<br>XT Chemistry Products<br>GLU-Ca Slides quantitatively<br>measures calcium (Ca)<br>concentration in serum,<br>plasma, and urine. | For <i>in vitro</i> diagnostic use only.<br><br>VITROS Chemistry Products GLU<br>Slides quantitatively measure<br>glucose (GLU) concentration in<br>serum, plasma, urine, and CSF.<br><br>VITROS Chemistry Products Ca<br>Slides quantitatively measure<br>calcium (Ca) concentration in<br>serum, plasma, and urine. |
| Device<br>Description | No Change | Multilayered, analytical element<br>coated on a polyester support |
| Basic Principle | No Change | GLU Colorimetric<br>Ca Colorimetric |
| Incubation time<br>and temperature | No Change | Approximately 5 minutes<br>37°C (98.6° F) |
| Sample type | No Change | GLU Serum, plasma, urine and<br>cerebrospinal fluid (CSF)<br>Ca Serum, plasma and urine |
| Amount of Slide<br>Reactive<br>Ingredients per<br>cm² (test) | No Change<br><br>The composition of the analytical<br>element of each test within the<br>VITROS XT Slide will remain<br>the same as that used in each<br>predicate device | GLU Glucose oxidase (Aspergillus sp.)<br>0.77 U; peroxidase (horseradish<br>root) 3.6 U; 1,7-<br>dihydroxynaphthalene (dye<br>precursor) 67 µg and 4-<br>aminoantipyrine hydrochloride<br>(dye precursor) 0.11 mg.<br>Ca Arsenazo III dye 60 ug |
| Summary of the technological characteristics of the device compared to the<br>predicate device | | |
| Device<br>Characteristic | New Device<br>VITROS XT GLU-Ca Slide<br>(New) | Predícate Devices<br>VITROS GLU Slide [k182072]<br>VITROS Ca Slide [k072440]<br>(Current) |
| Assay Range | No Change | GLU (mg/dL)<br>Serum/plasma 20 - 625<br>Urine 20 - 650<br>CSF 20 - 650<br><br>Ca (mg/dL)<br>Serum/plasma 1.0 - 14.0<br>Urine 1.0 – 17.8 |
| Calibrators | Same | VITROS Chemistry Products<br>Calibrator Kit 1 |
| Controls | Same | VITROS Chemistry Products<br>Performance Verifier I and II<br>VITROS Chemistry Products Liquid<br>Performance Verifier I and II |
| <b>Differences</b> | | |
| Instrumentation | VITROS XT 7600 Integrated<br>System | VITROS 250/350, 5,1 FS and 4600<br>Chemistry Systems<br>VITROS 5600 and XT 7600 |

# Summary of the technological characteristics of the device compared to the

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Integrated Systems

GLU

Ca

6 µL

10 µL

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#### Non-Clinical Testing Analytical Performance

GLU

Ca

#### Method Comparison

Sample volume

Method Comparison testing followed CLSI Protocol EP09c. Measurement Procedure Comparison and Bias Estimation Using Patient Samples. Serum, urine and cerebrospinal fluid (glucose only) samples were evaluated on the VITROS XT Chemistry Products GLU-Ca Slides using the VITROS XT 7600 Integrated System and on VITROS Chemistry Products GLU Slides and VITROS Chemistry Products Ca Slides using the VITROS 5600 Integrated System. The correlation between the predicate and the new tests within the VITROS XT GLU-Ca Slides on the VITROS XT 7600 Integrated System is summarized below.

2.7 µL

3.5 µL

Weighted Deming regressions were performed to determine the correlation for GLU (all fluid types) and Ca (urine). Ordinary Deming regression was performed to determine the correlation between the Ca serum methods.

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| Summary of Method Comparison Regression Analysis DataUnits mg/dL | | | | | | |
|------------------------------------------------------------------|-----|-------|-----------|--------------|------------|-----------------|
| Test | N | Slope | Intercept | Corr. Coeff. | Test Range | Measuring range |
| GLU Serum | 116 | 0.99 | -0.91 | 1.000 | 25 - 571 | 20 - 625 |
| GLU Urine | 103 | 1.01 | -0.18 | 1.000 | 24-642 | 20 - 650 |
| GLU CSF | 149 | 0.98 | -0.06 | 1.000 | 21-596 | 20 - 650 |
| Ca Serum | 112 | 0.99 | 0.04 | 0.999 | 1.4-13.9 | 1.0 - 14.0 |
| Ca Urine | 119 | 0.99 | 0.07 | 0.999 | 2.2-17.2 | 1.0 - 17.8 |

#### 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 GLU-Ca 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 and urine for the Ca test and serum, urine, and CSF for the GLU test. 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.

| GLU Serum Units (mg/dL) | | | | | | | | |
|-------------------------|----------------|-----|--------------|-----|---------------|-----|--------|--------|
| Mean | Repeatability* | | Within Day** | | Within Lab*** | | No. of | No. of |
| Conc. | SD | CV% | SD | CV% | SD | CV% | Obs. | Days |
| 42 | 0.3 | 0.6 | 0.4 | 1.0 | 0.4 | 1.0 | 80 | 20 |
| 87 | 0.4 | 0.4 | 0.8 | 0.9 | 0.8 | 0.9 | 80 | 20 |
| 105 | 0.5 | 0.4 | 1.0 | 0.9 | 1.0 | 0.9 | 80 | 20 |
| 121 | 0.6 | 0.5 | 1.3 | 1.1 | 1.4 | 1.2 | 80 | 20 |
| 292 | 0.9 | 0.3 | 2.4 | 0.8 | 2.6 | 0.9 | 80 | 20 |
| 573 | 2.0 | 0.4 | 5.0 | 0.9 | 5.3 | 0.9 | 80 | 20 |
| GLU Urine Units (mg/dL) | | | | | | | | |
| Mean | Repeatability* | | Within Day** | | Within Lab*** | | No. of | No. of |
| Conc. | SD | CV% | SD | CV% | SD | CV% | Obs. | Days |
| 26 | 0.3 | 1.2 | 0.5 | 1.8 | 0.5 | 1.9 | 80 | 20 |
| 43 | 0.3 | 0.7 | 0.4 | 1.0 | 0.5 | 1.1 | 80 | 20 |
| 44 | 0.4 | 0.8 | 0.5 | 1.0 | 0.5 | 1.1 | 80 | 20 |
| 114 | 0.5 | 0.5 | 0.7 | 0.6 | 0.7 | 0.6 | 80 | 20 |
| 292 | 1.5 | 0.5 | 1.7 | 0.6 | 1.7 | 0.6 | 80 | 20 |

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| GLU CSF Units (mg/dL) | | | | | | | | |
|---------------------------|----------------------|-----|--------------------|-----|---------------------|-----|----------------|----------------|
| Mean<br>Conc. | Repeatability*<br>SD | CV% | Within Day**<br>SD | CV% | Within Lab***<br>SD | CV% | No. of<br>Obs. | No. of<br>Days |
| 37 | 0.3 | 0.8 | 0.4 | 1.1 | 0.4 | 1.1 | 80 | 20 |
| 38 | 0.3 | 0.8 | 0.5 | 1.2 | 0.5 | 1.2 | 80 | 20 |
| 39 | 0.3 | 0.7 | 0.4 | 1.1 | 0.5 | 1.2 | 80 | 20 |
| 87 | 0.4 | 0.4 | 0.6 | 0.7 | 0.6 | 0.7 | 80 | 20 |
| 318 | 1.4 | 0.4 | 1.7 | 0.6 | 2.0 | 0.6 | 80 | 20 |
| 644 | 2.7 | 0.4 | 3.5 | 0.6 | 3.6 | 0.6 | 80 | 20 |
| Ca Serum Units (mg/dL) | | | | | | | | |
| Mean<br>Conc. | Repeatability*<br>SD | CV% | Within Day**<br>SD | CV% | Within Lab***<br>SD | CV% | No. of<br>Obs. | No. of<br>Days |
| 2.3 | 0.04 | 1.7 | 0.06 | 2.6 | 0.07 | 2.9 | 80 | 20 |
| 6.8 | 0.04 | 0.6 | 0.06 | 0.8 | 0.09 | 1.4 | 80 | 20 |
| 8.4 | 0.07 | 0.8 | 0.08 | 0.9 | 0.10 | 1.2 | 80 | 20 |
| 8.8 | 0.05 | 0.6 | 0.07 | 0.8 | 0.08 | 0.9 | 80 | 20 |
| 11.9 | 0.07 | 0.6 | 0.08 | 0.7 | 0.11 | 1.0 | 80 | 20 |
| 12.2 | 0.06 | 0.5 | 0.07 | 0.6 | 0.11 | 0.9 | 80 | 20 |
| Ca Urine<br>Units (mg/dL) | | | | | | | | |
| Mean<br>Conc. | Repeatability*<br>SD | CV% | Within Day**<br>SD | CV% | Within Lab***<br>SD | CV% | No. of<br>Obs. | No. of<br>Days |
| 2.1 | 0.05 | 2.3 | 0.07 | 3.5 | 0.07 | 3.4 | 80 | 20 |
| 5.0 | 0.04 | 0.7 | 0.05 | 1.0 | 0.06 | 1.1 | 80 | 20 |
| 5.6 | 0.05 | 0.8 | 0.06 | 1.1 | 0.07 | 1.2 | 80 | 20 |
| 6.6 | 0.04 | 0.6 | 0.07 | 1.1 | 0.09 | 1.3 | 80 | 20 |
| 9.7 | 0.08 | 0.8 | 0.08 | 0.8 | 0.10 | 1.1 | 80 | 20 |
| 15.7 | 0.11 | 0.7 | 0.16 | 1.0 | 0.28 | 1.8 | 80 | 20 |

*Repeatability (formerly called within-run precision) was determined using two replicates per run.

**Within Day precision was determined using two runs/day with two replications per run

***Within Lab precision was determined using a single lot of slides and a single calibration

#### Detection Limits

Detection capability studies for the GLU and Ca tests within the VITROS XT GLU-Ca Slides were evaluated according to CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures.

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LoQ determination was set on pre-defined total error (TE) goals based on the Westgard model, a combination of bias and precision. The Total Error goal used to accept the LoO for GLU was ≤ 4.8 mg/dL for serum, ≤ 3.9 mg/dL for urine and ≤ 4.6 mg/dL for CSF. The Total Error goal used to accept the LoQ for Ca was ≤ 0.15 mg/dL for serum and ≤ 0.42 mg/dL for urine.

| | GLU (mg/dL) | | | Ca (mg/dL) | |
|-------------|-------------|-------|------|------------|-------|
| | Serum | Urine | CSF | Serum | Urine |
| LOB | 1.0 | 2.5 | 1.0 | 0.10 | 0.05 |
| LOD | 1.9 | 3.0 | 1.9 | 0.14 | 0.09 |
| LOQ | 15.9 | 13.0 | 15.2 | 0.49 | 0.60 |
| Claimed LOQ | 20 | 20 | 20 | 1.0 | 1.0 |

The results of this analysis are summarized below:

#### Linearitv

Linearity studies were performed according to CLSI EP06-A, Evaluation of the Linearity of Ouantitative Measurement Procedures: A Statistical Approved Guideline (2003). VITROS XT GLU-Ca Slides were tested on the VITROS XT 7600 Integrated System. A series of twenty proportionally related admixtures of low and high test fluids were tested to verify linearity of the GLU and Ca serum and urine tests and the GLU CSF test; each sample was tested in quadruplicate. The linearity studies support the claimed measuring ranges for the individual tests within the VITROS XT GLU-Ca Slides.

| Assay | Fluid | Measuring Range<br>(mg/dL) | Linear Range<br>(mg/dL) |
|-------|--------------|----------------------------|-------------------------|
| GLU | Serum/plasma | 20-625 | 19.3-635.3 |
| | Urine | 20-650 | 15.4-776.1 |
| | CSF | 20-650 | 19.2-650.9 |
| Ca | Serum/plasma | 1.0-14.0 | 0.85-15.82 |
| | Urine | 1.0-17.8 | 0.75-20.67 |

Serum and plasma samples with values greater than the measuring range may be diluted with one part sample to one part diluent. A 7% BSA solution was found to be an acceptable diluent for the GLU test within the VITROS XT Chemistry Products GLU-Ca Slides. Isotonic saline and reagent-grade water were found to be acceptable diluents for the Ca test within the VITROS XT Chemistry Products GLU-Ca Slides.

Urine samples with values greater than the measuring range may be diluted with one part sample to one part diluent. Isotonic saline and reagent-grade water were found to be acceptable diluents for the GLU test within the VITROS XT Chemistry Products GLU-Ca Slides. Reagent-grade water was found to be an acceptable diluent for the Ca test within the VITROS XT Chemistry Products GLU-Ca Slides.

#### Expected Values

The expected values of the GLU and Ca tests within the VITROS XT GLU-Ca 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.

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#### GLU Reference Interval

GLU reference intervals for serum, urine and CSF are based on external studies 1.

| GLU Test Expected Values | |
|--------------------------|---------------|
| Serum | |
| Fasting adults | 74-100 mg/dL |
| Urine | |
| Random | 1-15 mg/dL |
| 24 hour | < 500 mg/day* |
| CSF | 40-70 mg/dL |

* Glucose concentration (mg/dL) x 24-hour volume (dL) = mg/day.

#### Ca Reference Interval

Ca reference intervals are based on external studies for serum and urine .

| Ca Test Expected Values | |
|----------------------------|-----------------|
| Serum | 8.6-10.3 mg/dL |
| Urine - Dietary Ca Intake: | |
| Ca-free | 5-40 mg/day* |
| Low to average | 50-150 mg/day* |
| Average | 100-300 mg/day* |

* Calcium concentration (mg/dL) x 24-hour volume (dL) = mg/day.

Each laboratory should confirm the validity of these intervals for the population it serves.

#### References

1. Tietz NW. Fundamentals of Clinical Chemistry and Molecular Diagnostics. 7ª ed. St. Louis: Elsevier; 2015.

2. Tietz NW (ed). Fundamentals of Clinical Chemistry. ed. 5. Philadelphia: WB Saunders; 968; 2001.

#### Specificity

The GLU and Ca tests within the VITROS XT Chemistry Products GLU-Ca Slides were screened for interfering substances following CLSI document EP07, 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 GLU-Ca Slides were made using the paired difference method. Dose-response analysis was conducted to characterize the degree of interference for each substance that interfered at the initial EP37 level screening test, and expected bias was reported at the lowest test level which did not meet acceptance criteria for bias as shown in the product claims.

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#### GLU Test

For the GLU test within VITROS XT GLU-Ca Slides, interference was observed for three (3) substances with serum. 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.

| GLU Serum Known Interfering Substances | | | | | |
|----------------------------------------|------------------------------|-------------------------------------|-----------------|--|--|
| Interferent | Interferent<br>Concentration | Glucose<br>Concentration<br>(mg/dL) | Bias<br>(mg/dL) | | |
| Glutathione | 92 mg/dL | 73 | -10.4 | | |
| Hemoglobin | 1000 mg/dL | 79 | 7.6 | | |
| Total Protein | 15 g/dL | 74 | 8.8 | | |
| | | 217 | 20.4 | | |

- . When using samples with visible hemolysis (Hb > 200 mg/dL), there may be a negative bias due to catalase released from the lysis of red blood cells. The VITROS XT Systems can perform Sample Indices using the MicroSensor module, and the GLU result from samples with visible hemolysis will be flagged with H (Hemolysis).
- Elevated lipids may limit diffusion of oxygen to the reactants. Dilute grossly lipemic samples twofold before analysis.

Interference was observed with four (4) substances tested in urine.

| GLU Urine Known Interfering Substances | | | |
|----------------------------------------|------------------------------|-------------------------------------|-----------------|
| Interferent | Interferent<br>Concentration | Glucose<br>Concentration<br>(mg/dL) | Bias<br>(mg/dL) |
| Ascorbic acid | 50 mg/dL | 31 | -14.0 |
| Ascorbic acid | 13 mg/dL | 171 | -13.7 |
| Dextran | 7.5 g/dL | 31 | 8.0 |
| Dextran | 2.5 g/dL | 169 | 14.4 |
| Hemoglobin | 250 mg/dL | 33 | 8.5 |
| N-Acetylcysteine | 25 mg/dL | 166 | -14.0 |

{12}------------------------------------------------

| GLU CSF Known Interfering Substances | | | |
|--------------------------------------|------------------------------|----------------------------------|-----------------|
| Interferent | Interferent<br>Concentration | Glucose Concentration<br>(mg/dL) | Bias<br>(mg/dL) |
| Hemoglobin | 250 mg/dL | 47 | 5.0 |
| Hemoglobin | 1000 mg/dL | 69 | 12.1 |
| Hemoglobin | 1000 mg/dL | 87 | 10.2 |

One (1) substance was tested and found to cause interference in cerebrospinal fluid (CSF).

For the GLU test within VITROS XT GLU-Ca Slides, no interference was observed for seventy-nine (79) substances tested in serum, bias < 7.0 mg/dL at approximately 80 mg/dL glucose and bias < 14 mg/dL at approximately 200 mg/dL glucose. No interference was observed for eighteen (18) substances tested in urine, bias < 7.0 mg/dL at approximately 30 mg/dL glucose and bias < 11.9 mg/dL at approximately 170 mg/dL glucose.

#### Ca Test

For the Ca test within VITROS XT GLU-Ca Slides, interference was observed for seven (7) substances with serum. 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.

| Ca Serum Known Interfering Substances | | | |
|---------------------------------------|------------------------------|----------------------------------|-----------------|
| Interferent | Interferent<br>Concentration | Calcium Concentration<br>(mg/dL) | Bias<br>(mg/dL) |
| Cefoxitin | 663 mg/dL | 7.7 | 0.28 |
| Cefoxitin | 663 mg/dL | 11.3 | 0.50 |
| Cholesterol | 525 mg/dL | 6.3 | 0.34 |
| Cholesterol | 625 mg/dL | 9.5 | 0.34 |
| Gadodiamide | 86 mg/dL | 7.4 | 0.35 |
| Hemoglobin | 1000 mg/dL | 8.3 | -0.30 |
| Sodium | 391 mg/dL | 7.4 | 0.35 |
| Sodium | 391 mg/dL | 11.1 | 0.52 |
| Sorbitol | 1800 mg/dL | 11.9 | -0.37 |
| Total Protein | 15 g/dL | 12.1 | -0.45 |

For the Ca test within VITROS XT GLU-Ca Slides, no interfering compounds were observed for urine. For the Ca test within VITROS XT GLU-Ca Slides, no interference was observed for seventy-five (75) substances tested in serum, bias < 0.23 mg/dL at approximately 8 mg/dL calcium and bias < 0.27 mg/dL at approximately 12 mg/dL calcium. No interference was observed for twenty (20) substances tested in urine, bias < 0.79 mg/dL at approximately 5 mg/dL calcium and bias < 1.2 mg/dL at approximately 12 mg/dL calcium.

{13}------------------------------------------------

#### Other Limitations

Keeping the sample in an open container at room temperature may increase the reported calcium concentration by up to 0.4 mg/dL. Changes are due to the loss of carbon dioxide, which results in an increase in pH of the specimen. The increase in pH is minimized by anaerobic handling procedures followed by prompt analysis. Adherence to these procedures is especially important for pediatric samples where the sample volume is small. Certain drugs and clinical conditions are known to alter glucose and calcium 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 GLU-Ca 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.