VITROS CHEMISTRY PRODUCTS CO2 DT SLIDES; VITROS CHEMMISTRY PRODUCTS DT CALIBRATOR KIT, MODELS CO2 DT SLIDES, 172 0002;

K093611 · Ortho-Clinical Diagnostics, Inc. · KHS · Apr 15, 2010 · Clinical Chemistry

Device Facts

• Record ID: K093611
• Device Name: VITROS CHEMISTRY PRODUCTS CO2 DT SLIDES; VITROS CHEMMISTRY PRODUCTS DT CALIBRATOR KIT, MODELS CO2 DT SLIDES, 172 0002
• Applicant: Ortho-Clinical Diagnostics, Inc.
• Product Code: KHS · Clinical Chemistry
• Decision Date: Apr 15, 2010
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1160
• Device Class: Class 2

Indications for Use

VITROS Chemistry Products CO₂ DT Slides quantitatively measure carbon dioxide (CO₂) concentration in serum and plasma using VITROS DT60 and DT60 II Chemistry Systems. Total carbon dioxide measurements are used in the diagnosis and treatment of numerous potentially serious disorders associated with changes in body acid-base balance. For in vitro diagnostic use only.

Device Story

The VITROS Chemistry Products CO2 DT Slide is a multilayered analytical element for in vitro diagnostic measurement of ionic carbon dioxide in serum and plasma. The device uses direct potentiometry; 10 uL of reference fluid and 10 uL of sample fluid are deposited on separate halves of the slide. A paper bridge forms a liquid junction between the fluids, allowing ion migration to silver/silver chloride layers to establish equilibrium. The VITROS DT60/DT60 II Chemistry System electrometer measures the potential difference between reference and indicator electrodes. A microprocessor calculates CO2 concentration (mmol/L) using stored calibration parameters. The device is used in clinical laboratory settings. Results assist healthcare providers in diagnosing and managing acid-base balance disorders.

Clinical Evidence

Bench testing only. Precision study (n=84 per level) showed CV% 1.9-3.0%. Linearity confirmed across 5-50 mmol/L range (r=0.999). Method comparison against predicate using 119 clinical samples yielded y = 0.975x + 0.48 (r² = 0.978). Interference testing evaluated numerous endogenous/exogenous substances; specific biases noted for iodide, bromide, and nitrate. Matrix comparison across five tube types showed 100% of samples within ± 3 mmol/L of reference.

Technological Characteristics

Dry, multilayered slide on polyester support. Sensing principle: direct potentiometry via ion-selective electrodes. Reactive ingredients: silver, silver chloride, sodium chloride, potassium chloride, trioctylpropylammonium chloride, decyltrifluoroacetophenone. ISE baseweb manufactured via magnetic sputter deposition. Nickel-chromium (80% Ni, 20% Cr) stripes. Measuring range: 5-50 mmol/L. Designed for VITROS DT60/DT60 II Chemistry Systems.

Indications for Use

Indicated for the quantitative measurement of CO2 in serum and plasma for the diagnosis and treatment of disorders associated with acid-base balance changes in patients.

Regulatory Classification

Identification

A bicarbonate/carbon dioxide test system is a device intended to measure bicarbonate/carbon dioxide in plasma, serum, and whole blood. Bicarbonate/carbon dioxide measurements are used in the diagnosis and treatment of numerous potentially serious disorders associated with changes in body acid-base balance.

Predicate Devices

• VITROS Chemistry Products CO2 DT Slides (k802376)

Submission Summary (Full Text)

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510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
ASSAY ONLY TEMPLATE

A. 510(k) Number:
k093611

B. Purpose for Submission:
Modification to a marketed device (k802376)

C. Measurand:
Carbon dioxide

D. Type of Test:
Quantitative, potentiometric

E. Applicant:
Ortho-Clinical Diagnostics, Inc.

F. Proprietary and Established Names:
VITROS Chemistry Products CO₂ DT Slide assay
Bicarbonate / carbon dioxide assay

G. Regulatory Information:
1. Regulation section:
21 CFR 862.1160, Bicarbonate/carbon dioxide test system
2. Classification:
Class II
3. Product code:
KHS
4. Panel:
Clinical Chemistry (75)

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H. Intended Use:

1. Intended use(s):

See indication(s) for use below.

2. Indication(s) for use:

VITROS Chemistry Products CO₂ DT Slides quantitatively measure carbon dioxide (CO₂) concentration in serum and plasma using VITROS DT60 and DT60 II Chemistry Systems. Total carbon dioxide measurements are used in the diagnosis and treatment of numerous potentially serious disorders associated with changes in body acid-base balance. For in vitro diagnostic use only.

3. Special conditions for use statement(s):

For prescription use only

4. Special instrument requirements:

For use on the VITROS DT60 and DT60 II Chemistry Systems only

I. Device Description:

The VITROS CO₂ DT Slide method is performed using the VITROS CO₂ DT Slides and the VITROS Chemistry Products DT Calibrator Kit on VITROS DT60/DT60 II Chemistry Systems.

The VITROS DT60/DT60II Chemistry Systems and reagents are designed specifically for use with the VITROS Chemistry Products range of products. The following materials are required to perform a carbon dioxide test on the VITROS DT60/DT60 II Chemistry System:

- VITROS DT60/DT60 II Chemistry System
- VITROS Chemistry Products CO₂ DT Slides:

**Reactive ingredients**

Silver 0.4 mg; silver chloride 0.2 mg; sodium chloride 0.2 mg; potassium chloride 63 μg; trioctylpropylammonium chloride 0.5 mg; and decyltrifluoroacetophenone 0.8 mg.

**Other ingredients**

Binders, plasticizers, surfactants, stabilizer, buffers, nickel-chromium and cross-linking agent.

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- VITROS Chemistry Products DT Calibrator Kit (cleared under k841503)
- VITROS Chemistry Products DT Electrolyte Diluent
- VITROS DT Reference Fluid

# J. Substantial Equivalence Information:

1. Predicate device name(s):

VITROS Chemistry Products $\mathrm{CO}_{2}$ DT Slides

2. Predicate $510(\mathbf{k})$ number(s):

k802376

3. Comparison with predicate:

| Similarities | | |
| --- | --- | --- |
| Item | New Device VITROS Chemistry Products CO2 DT Slide (Modified) | Predicate Device VITROS Chemistry Products CO2DT Slide |
| Intended Use | Same | For in vitro diagnostic use only. VITROS CO2 DT Slides quantitatively measure carbon dioxide (CO2) concentration in serum and plasma. |
| Fundamental scientific technology | Same | Dry, multilayered slide utilizing direct potentiometry |
| Reactive Ingredients per square cm | Same | Silver 0.4 mg; silver chloride 0.2 mg; sodium chloride 0.2 mg; potassium chloride 63 μg; trioctylpropylammonium chloride 0.5 mg; and decyltrifluoroacetophenone 0.8 mg. |
| Sample type | Same | Serum, plasma |
| Instrumentation | Same | VITROS DT Systems |
| Measuring Range | Same | 5 – 50 mmol/L |
| Reference Range | Same | 22 – 30 mmol/L |

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| Differences | | |
| --- | --- | --- |
| Item | New Device VITROS Chemistry Products CO_{2} DT Slide (Modified) | Predicate Device VITROS Chemistry Products CO_{2}DT Slide |
| Manufacturing Process of the ISE baseweb (Ag/AgCl and Support Layers of the Na+ DT Slide) | Magnetic sputter deposition | Electron beam evaporation |
| Composition of ISE baseweb component | Ag/AgCl concentration: No change; Nickel Stripes: NiCr (80% Nickel, 20% Chromium) | Ag/AgCl concentration: Silver 0.4 mg and silver chloride 0.2 mg Nickel Stripes: Ni (99+% Nickel) |

## K. Standard/Guidance Document Referenced (if applicable):

- Interference Testing in Clinical Chemistry; Approved Guideline (CLSI EP 7-A)
- Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline (CLSI EP09-A2)
- Evaluation of Precision Performance of Clinical Chemistry Devices; Approved Guideline (CLSI EP5-A)
- Protocols for Determination of Limits of Detection and Limits of Quantitation (CLSI EP17-A)

## L. Test Principle:

The VITROS CO₂ DT Slide method is performed using the VITROS CO₂ DT Slides and the VITROS Chemistry Products DT Calibrator Kit on VITROS DT60/DT60 II Chemistry Systems. The VITROS CO₂ DT Slide is a multilayered, analytical element coated on a polyester support that uses direct potentiometry for measurement of ionic carbon dioxide.

The slide consists of two ion-selective electrodes, each containing a buffer layer, an ion selective membrane layer, a reference layer, and a silver and a silver chloride layer coated on a polyester support. The buffer layer adjusts the sample pH to 8.4 and maintains CO₂, HCO₃⁻, and CO₃⁻ in proper equilibrium. The ion-selective membrane layer contains an ion exchanger trioctylpropylammonium chloride (TOPA Cl) and a CO₃⁻ ionophore decyltrifluoroacetophenone (DTFA). A drop of patient sample and a drop of VITROS DT Reference Fluid on separate halves of the slide results in migration of both fluids toward the center of the paper bridge. A stable liquid junction is formed connecting the reference electrode to the sample indicator electrode. Each electrode produces an electrical potential in response to the concentration of carbon dioxide applied to it. The potential difference poised between the two electrodes is proportional to the carbon dioxide concentration in the sample.

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M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

The precision study was performed using two quality control fluids and two levels of calibrator fluids. Samples were analyzed in duplicate, twice a day for 21 days. One VITROS DT 60 II instrument was used to collect the data. Results are summarized below:

| Concentration (mmol/L) | Within Day SD | Within Day CV% | Within Lab SD | Within Lab CV% | n |
| --- | --- | --- | --- | --- | --- |
| 10 | 0.2 | 2.0 | 0.2 | 2.0 | 84 |
| 20 | 0.6 | 3.0 | 0.6 | 3.0 | 84 |
| 25 | 0.6 | 2.4 | 0.7 | 2.8 | 84 |
| 36 | 0.7 | 1.9 | 0.9 | 2.5 | 84 |

b. Linearity/assay reportable range:

The measuring range of the $\mathrm{CO}_{2}$ assay is $5 - 50\ \mathrm{mmol/L}$. A linearity study was performed as follows. Two serum pools were prepared with total carbon dioxide concentrations near the extremes of the calibration range. The high pool was $7\%$ BSA with an approximate $\mathrm{CO}_{2}$ concentration of $62.7\ \mathrm{mmol/L}$. The low pool was $7\%$ BSA with an approximate $\mathrm{CO}_{2}$ concentration of $0.5\ \mathrm{mmol/L}$. The low and high pools were mixed to obtain six admixtures of intermediate concentrations. Two to four determinations of the six admixtures were tested on the VITROS DT60 II Chemistry System. The experiment was performed three times, each test using one reagent lot of $\mathrm{CO}_{2}$ slides. The measured $\mathrm{CO}_{2}$ values were plotted as the dependent variable against the $\%$ high pool values as the independent variable. Linear regression produced the following:

Lot 1 $y = 0.94x + 3$ $r = 0.999$

Lot 2 $y = 0.96x + 3$ $r = 0.999$

Lot 3 $y = 0.94x + 4$ $r = 0.999$

c. Traceability, Stability, Expected values (controls, calibrators, or methods):

Unopened VITROS $\mathrm{CO}_{2}$ DT Slides are stable until the expiration date on the carton when stored refrigerated $(2-8^{\circ}\mathrm{C})$ or frozen $(\leq-18^{\circ}\mathrm{C})$, and for less than 48 hours when stored at room temperature $(18-28^{\circ}\mathrm{C})$. Once opened, the VITROS $\mathrm{CO}_{2}$ Slides are stable at room temperature $(18-28^{\circ}\mathrm{C})$ for up to 15 minutes.

d. Detection limit:

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The sponsor performed Limit of Blank (LOB), Limit of Detection (LOD) and Limit of Quantitation (LOQ) studies based on the CLSI EP17-A guideline.

LOB determinations were made using an ultra filtered plasma sample devoid of analyte on four reagent lots of VITROS CO₂ DT Slides. Sample was assayed in 20 replicates per day for five test days on one VITROS DT60II Chemistry System for a total of 100 replicates for each lot. LOB was determined to be 5.0 mmol/L.

LOD and LOQ was determined for four reagent lots of VITROS CO₂ DT Slides by evaluation of three low plasma samples having concentrations near or greater than the LOB by increments of approximately two standard deviations. Samples were assayed 10 replicates per day over five days on two VITROS DT60 II Chemistry Systems for a total of 50 replicates. LOD and LOQ were determined to be 5.0 mmol/L.

The claimed measuring range of the candidate device is 5 to 50 mmol/L.

e. Analytical specificity:

Interference studies were performed using clinical serum samples to determine the effect of various endogenous and exogenous substances using VITROS DT 60 II analyzer. The following equations were used by the sponsor to calculate bias:

For exogenous substances: Bias = ("spike": mean concentration of interfering substance pool) – ("blank": mean concentration of "control" pool).

For endogenous substances: Bias = (mean concentration of VITROS method) – (mean concentration of reference method).

The following substances were tested with the VITROS CO₂ DT Slides at a carbon dioxide concentration of 28 mmol/L and found to cause a bias of ≤ 2 mmol/L at the concentration shown.

| Compound | Concentration | |
| --- | --- | --- |
| acetaminophen | 20 mg/dL | 1.3 mmol/L |
| acetylsalicylic acid | 35 mg/dL | 1.9 mmol/L |
| alprazolam | 20 μg/dL | 648 nmol/L |
| 5 - aminosalicylic acid | 23 mg/dL | 1.5 mmol/L |
| amitriptyline | 1 μg/mL | 3.6 μmol/L |
| amoxicillin | 1500 μg/mL | 4.1 mmol/L |
| ascorbic acid | 3 mg/dL | 170 μmol/L |
| atenolol | 20 μg/mL | 75.1 μmol/L |
| bilirubin | 40 mg/dL | 684 μmol/L |
| calcium | 16 mg/dL | 4 mmol/L |

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| Compound | Concentration | |
| --- | --- | --- |
| carbamazepine | 60 μg/mL | 254 μmol/L |
| cephalexin | 400 μg/mL | 1.2 mmol/L |
| ciprofloxacin | 5 mg/dL | 151 μmol/L |
| clarithromycin | 25 mg/dL | 334 μmol/L |
| codeine | 4 μg/mL | 13.4 μmol/L |
| dextran | 3000 mg/dL | 750 μmol/L |
| dextromethorphan | 3.8 μg/mL | 14.0 μmol/L |
| digoxin | 3 μg/dL | 38.4 nmol/L |
| diltiazem | 5 μg/mL | 12.1 μmol/L |
| diphenhydramine | 10 μg/mL | 39.1 μmol/L |
| enalapril | 1.2 μg/mL | 3.2 μmol/L |
| ethanol | 394 mg/dL | 85.7 mmol/L |
| fluoxetine | 0.8 mg/dL | 25.9 μmol/L |
| furosemide | 10 mg/dL | 302 μmol/L |
| gentisic acid | 0.5 mg/dL | 32.4 μmol/L |
| glucose | 600 mg/dL | 33.3 mmol/L |
| glutathione | 1 mg/dL | 32.5 μmol/L |
| glyburide | 6.4 μg/mL | 13.0 μmol/L |
| guaifenesin | 100 mg/dL | 5 mmol/L |
| hemoglobin | 1000 mg/dL | 10 g/L |
| hydrochlorothiazide | 2 mg/dL | 67.2 μmol/L |
| hydrocodone | 250 ng/mL | 835 nmol/L |
| ibuprofen | 70 mg/dL | 3.4 mmol/L |
| intralipid | 800 mg/dL | 8 g/L |
| isoniazid | 0.4 mg/dL | 29.2 μmol/L |
| L-dopa | 0.6 mg/dL | 30.4 μmol/L |
| lithium | 1 mEq/L | 1 mmol/L |
| loratadine | 100 ng/mL | 261 nmol/L |
| magnesium | 4.5 mg/dL | 1.85 mmol/L |
| meprobamate | 2 mg/dL | 91.6 μmol/L |
| 6-mercaptopurine | 1.5 mg/dL | 98.5 μmol/L |
| naproxen | 900 μg/mL | 3.9 mmol/L |
| nifedipine | 0.2 mg/dL | 5.8 μmol/L |
| omeprazole | 20 mg/dL | 579 μmol/L |
| phenobarbital | 3 mg/dL | 129 μmol/L |
| phenytoin | 10 mg/dL | 396 μmol/L |
| phospholipids as lecithin | 500 mg/dL | 5 g/L |
| prednisone | 0.1 mg/dL | 2.8 μmol/L |
| propoxyphene | 0.4 mg/dL | 11.8 μmol/L |
| pseudoephedrine | 20 μg/mL | 121 μmol/L |
| ranitidine | 20 μg/mL | 63.8 μmol/L |

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| Compound | Concentration | |
| --- | --- | --- |
| simvastatin | 500 mg/L | 1.2 mmol/L |
| sulfamethoxazole | 40 mg/dL | 1.6 mmol/L |
| sulfathiazole | 6 mg/dL | 235 μmol/L |
| terazosin | 1 mg/dL | 25.8 μmol/L |
| tolbutamide | 22 mg/dL | 814 μmol/L |
| total protein | 4 g/dL | 40 g/L |
| total protein | 10 g/dL | 100 g/L |
| triamterene | 6 mg/dL | 237 μmol/L |
| triglycerides | 800 mg/dL | 9 mmol/L |
| trimethoprim | 40.1 μg/mL | 138 μmol/L |
| tyrosine | 24 mg/dL | 1.3 mmol/L |
| urea | 214 mg/dL | 35.7 mmol/L |
| warfarin | 10.7 mg/dL | 347 μmol/L |

Iodide was tested at a carbon dioxide concentration of 25 mmol/L and found to cause a bias of 6 mmol/L CO₂ at an iodide concentration of 2 mmol/L. This is noted in the labeling.

In the labeling, the sponsor also notes the following:

- Lactate, hippurate, and other organic acids at significantly elevated concentrations have been reported to increase CO₂ results.
- Bromide from therapeutic drugs and ointments may cause a positive bias of approximately 2 mmol/L for each mmol of bromide.
- Nitrate may cause a positive bias of approximately 3 mmol/L for each mmol of nitrate.

f. Assay cut-off:

Not applicable.

2. Comparison studies:

a. Method comparison with predicate device:

A comparison of 119 samples, ranging in concentration from 8 to 49 mmol/L, was performed using the new device on the VITROS DT 60 II analyzer and the predicate. Spiked, diluted, and unaltered clinical samples were analyzed. The linear regression line was calculated, with the following results:

$$
y = 0.975x + 0.48
$$

$$
r^2 = 0.978
$$

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b. Matrix comparison:

The assay may be performed using serum, lithium heparin plasma, or sodium heparin plasma. To demonstrate this, the sponsor performed a study in which five tube types (plain serum red top, serum separator tubes (SST), LiHep tubes, NaHep tubes, and LiHep plasma separator tubes (PST)) were collected from each of 10 individual donors. Serum or plasma was separated from the cells. The bias for each tube type was calculated using the plain serum red top as the reference when analyzed using the VITROS DT 60 II analyzer. Across all tube types, 63% of the comparisons to the reference red top tube were with ± 1 mmol/L, 89% were ± 2 mmol/L, and 100% were within ± 3 mmol/L.

3. Clinical studies:

a. Clinical Sensitivity:

Not applicable.

b. Clinical specificity:

Not applicable.

c. Other clinical supportive data (when a. and b. are not applicable):

4. Clinical cut-off:

Not applicable.

5. Expected values/Reference range:

22 – 30 mmol/L from Tietz NW (ed). Fundamentals of Clinical Chemistry. ed. 4. Philadelphia: WB Saunders; 780; 1996.

N. Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

O. Conclusion:

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.