ELITECH CLINICAL SYSTEMS CARBON DIOXIDE ELECTRODE, ELITECH CLINICAL SYSTEMS ISE CALIBRATORS

K111960 · Elitechgroup · KHS · Nov 18, 2011 · Clinical Chemistry

Device Facts

• Record ID: K111960
• Device Name: ELITECH CLINICAL SYSTEMS CARBON DIOXIDE ELECTRODE, ELITECH CLINICAL SYSTEMS ISE CALIBRATORS
• Applicant: Elitechgroup
• Product Code: KHS · Clinical Chemistry
• Decision Date: Nov 18, 2011
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1160
• Device Class: Class 2

Intended Use

The carbon dioxide electrode for the ELITech Clinical Systems Selectra ProM is intended for use for the quantitative in vitro diagnostic determination of Total CO2 in human serum and plasma. Bicarbonate/carbon dioxide measurements are used in the diagnosis and treatment of numerous potentially serious disorders associated with changes in body acid-base balance. ELITech Clinical Systems ISE Calibrators are used for the calibration of sodium (Na+), potassium (K+), chloride (Cl-) and carbon dioxide (Total CO2) on ELITech Clinical Systems Selectra ProM analyzer equipped with ISE module.

Device Story

The ELITech Clinical Systems ISE Total CO2 Electrode system is an accessory for the Selectra ProM analyzer. It utilizes indirect potentiometry with an Ion-Selective Electrode (ISE) to measure carbon dioxide levels in human serum or lithium heparinized plasma. The system includes electrodes, ISE reference solution, ISE diluent, and ISE calibrators. The device is operated by laboratory personnel in a clinical setting. The analyzer processes the electrochemical signals from the electrode to provide a quantitative concentration of CO2. Healthcare providers use these results to diagnose and monitor metabolic and respiratory acid-base disorders. The device benefits patients by providing rapid, accurate electrolyte and CO2 data necessary for clinical decision-making regarding fluid and electrolyte therapy.

Clinical Evidence

No clinical data. Bench testing only. Precision studies (N=80) showed within-run CV 2.3-3.9% and total CV 5.2-6.8%. Linearity confirmed 10.8–43.0 mEq/L (r=0.9998). Method comparison (N=99) against predicate yielded y = 0.908x + 2.2 (r=0.985). Matrix comparison (N=40) confirmed lithium heparin plasma equivalence to serum (r=0.995). Interference testing performed per CLSI EP7-A.

Technological Characteristics

Indirect potentiometry using Ion-Selective Electrodes (ISE). Reagents include buffered solution with surfactant and 1.75 mmol/L CO2. Calibration via multi-analyte aqueous solutions traceable to NIST SRM 924a (CO2), 919b (Na+), and 918b (K+/Cl-). System is designed for the Selectra ProM analyzer. Storage requirements: 10-30 °C for reference solution, 2-30 °C for calibrators. No performance standards under Section 514 finalized.

Indications for Use

Indicated for quantitative in vitro diagnostic determination of Total CO2 in human serum and plasma for patients requiring assessment of acid-base balance. Used for diagnosis and treatment of disorders associated with acid-base changes.

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

• Roche Diagnostics CO2-L, Bicarbonate liquid (k031879)
• Roche Diagnostics Ammonia/Ethanol/CO2 calibrator (k031879)

Submission Summary (Full Text)

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510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
ASSAY AND INSTRUMENT COMBINATION TEMPLATE

A. 510(k) Number:
k111960

B. Purpose for Submission:
New Device

C. Measurand:
Carbon dioxide (CO2)

D. Type of Test:
Quantitative

E. Applicant:
ELITech Vital Scientific

F. Proprietary and Established Names:
ELITech Clinical Systems ISE Total CO2 Electrode
ELITech Clinical Systems ISE Calibrators

G. Regulatory Information:

| Name | Regulation section: | Classification: | Product code: | Panel: |
| --- | --- | --- | --- | --- |
| ELITech Clinical Systems ISE Total CO2 Electrode | 21 CFR 862.1160 | Class II | KHS | Chemistry 75 |
| ELITech Clinical Systems ISE Calibrators | 21 CFR 862.1150 | Class II | JIX | Chemistry 75 |

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H. Intended Use:

1. Intended use(s):

See Indications for Use

2. Indication(s) for use:

ISE CO2 electrode:

The carbon dioxide electrode for the ELITech Clinical Systems Selectra ProM is intended for use for the quantitative in vitro diagnostic determination of Total CO2 in human serum and plasma. Bicarbonate/carbon dioxide measurements are used in the diagnosis and treatment of numerous potentially serious disorders associated with changes in body acid-base balance

ELITech Clinical Systems ISE CALIBRATORS:

ELITech Clinical Systems ISE Calibrators are used for the calibration of sodium (Na+), potassium (K+), chloride (Cl-) and carbon dioxide (Total CO2) on ELITech Clinical Systems Selectra ProM analyzer equipped with ISE module.

3. Special conditions for use statement(s):

For prescription use only

4. Special instrument requirements:

ELITech Clinical Systems Selectra Pro M analyzer

I. Device Description:

The ELITech Clinical Systems ISE Total CO2 is a dry electrode system that employs the principle of indirect potentiometry measurement using a Total CO2 Ion-Selective Electrode installed in the ISE module of equipped Selectra analyzers along with liquid reagents. Total CO2 reagent system is composed of two (2) different reagent kits:

ISE Diluent: Diluent is supplied in liquid ready-to-use form and consists in a buffered solution with surfactant.

ISE Reference Solution: Solution is supplied in liquid ready-to-use form and consists in a buffered solution with surfactant containing sodium, potassium, chloride and carbon dioxide.

The ELITech Clinical Systems ISE Calibrators consists of 2 levels, CAL L and CAL H. Calibrators are supplied in liquid ready-to-use form and are aqueous solutions containing sodium, potassium, chloride and Total CO2. ELITech Clinical Systems ISE Calibrators were previously cleared for sodium, potassium and chloride in k102647.

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J. Substantial Equivalence Information:

1. Predicate device name(s):
Roche Diagnostics CO2-L, Bicarbonate liquid.
Roche Diagnostics Ammonia/Ethanol/CO2 calibrator.

2. Predicate 510(k) number(s):
k031879

3. Comparison with predicate:

| | ELITech Clinical Systems Device
(Candidate device) | Predicate device
(ROCHE Diagnostics CO2-L, Bicarbonate liquid and Roche Diagnostics calibrators, Ammonia/Ethanol/CO2 |
| --- | --- | --- |
| Intended use/Indication for Use | Same | It is intended for the quantitative determination of carbon dioxide in serum and plasma Bicarbonate/Carbon dioxide measurements are used in the diagnosis and treatment of numerous potentially serious disorders associated with changes in body acid-base balance. |
| Assay protocol | Indirect, potentiometry measurement with Ion-Selective Electrode | Enzymatic colorimetric test |
| Sample type | Serum and lithium heparin plasma | Same |
| Expected values | 23-29 mEq/L | 22-29 mmol/L |
| Measuring range | 10.8 – 43.0 mEq/L | 0.5-50 mmol/L |
| Traceability | According to the following reference material: Total CO2: NIST SRM 924a | This method has been standardized against primary standard traceable to NIST or NERL. |

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| ISE Calibrators | Composition: Aqueous solutions containing sodium, potassium, chloride and total CO2 with 2 different levels of concentrations. Concentrations are lot-specific. The values are given in the vial labels. Storage: Store at 2-30 °C. Stability: - After opening, calibrators is stable 30 days when stored at 2-30 °C capped to prevent contamination and evaporation. | Calibrator kit Composition: Aqueous buffer solution containing ammonia, ethanol and sodium bicarbonate with preservative. Liquid ready-to-use calibrators The concentrations of the calibrators components have been adjusted to ensure optimal calibration of the appropriate Roche methods on clinical chemistry analyzers. Storage Store at 2-8°C. Stability: - After opening, calibrators are stable 8 weeks when stored at 2-8 °C provided that dispensing of the calibrator takes place without microbial contamination, e.g. by pouring out . |
| --- | --- | --- |

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

| Number | Title |
| --- | --- |
| EP05-A2 | CLSI Evaluation of precision performance of quantitative measurement methods; Approved guideline – Second Edition |
| EP06-A | CLSI Evaluation of the linearity of the measurement of quantitative procedures: a statistical approach |
| EP07-A2 | CLSI Interference Testing in Clinical Chemistry; Approved Guideline, Second Edition |
| EP09-A2 | CLSI Method comparison and Bias estimation using patient samples; Approved guideline, Second Edition |

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| 13640:2002 | FDA Guidance Document ”Stability Testing of in vitro Diagnostic Reagents” |
| --- | --- |

## L. Test Principle:

Indirect potentiometric measurement with Ion-Selective Electrode i.e., ISE measurements are based on the potentiometric and Nernst Equation principle. The sample is diluted with a diluent and aspirated into ion-selective electrodes. The measured potential difference between the reference electrode and the ion specific electrodes is proportional to the Logarithm of the concentration of the measured ions.

## M. Performance Characteristics (if/when applicable):

### 1. Analytical performance:

#### a. Precision/Reproducibility:

Precision studies were performed with three pooled human serum samples at three different concentrations of CO2, on two separate Selectra ProM analyzers, over twenty operating days. Samples were tested in duplicate twice a day (N=80). The results are summarized in the tables below:

**Within-run**

| | n | Mean (mEq/L) | Within-run SD | Within-run CV% |
| --- | --- | --- | --- | --- |
| Low level | 80 | 12.1 | 0.5 | 3.9 |
| Medium level | 80 | 19.9 | 0.5 | 2.3 |
| High level | 80 | 27.5 | 0.6 | 2.3 |

**Total precision**

| | n | Mean (mEq/L) | Total SD | Total CV% |
| --- | --- | --- | --- | --- |
| Low level | 80 | 12.1 | 0.8 | 6.8 |
| Medium level | 80 | 19.9 | 1.1 | 5.4 |
| High level | 80 | 27.5 | 1.4 | 5.2 |

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b. Linearity/assay reportable range:

The linearity of CO2 System was studied by mixing a sample with high value (43.0 mEq/L) and a sample with low value (10.8 mEq/L) to obtain 11 levels with equidistant concentrations of CO2. All samples were tested in triplicate on the Selectra ProM analyzer. The expected values were plotted against the observed values and a linear regression line was fitted with the following regression:

$$
Y = 1.0387 - 0.9 \text{ mEq/L}
$$

$$
r = 0.9998
$$

The Standard error of the estimate, Sy.x is equal to 0.2 mEq/L.

The results of the linearity study support the CO2 assay measuring range from 10.8 to 43.0 mEq/L

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

**Traceability**

CO2 value is traceable to the Standard Reference Material SRM 924a (of the National Institute of Standards and Technology).

**Stability:**

Calibrator material is purchased from a commercial vendor (previously cleared under k033501). The sponsor claimed the following for stability: ELITech Clinical Systems ISE Calibrators is stable until the expiration date printed on the label when stored at 2-8°C prior to reconstitution. After reconstitution the stability is 8 hours when stored at 15-25°C, 2 days at 2-8°C or 4 weeks (when frozen once) at -25° and -15°C. The labeling stated that the Calibrators should be stored tightly capped and protected from light when not in use.

**Value Assignment**

ELITech Clinical Systems ISE Calibrators are value assigned using multiple Vital Scientific Selectra ProM analyzers. Each sample is tested in triplicate over several days. The target value of Level I and II are the median of the observed values range. After validation of the target value, a confidence range (high and low values) is then calculated.

It is recommended to recalibrate after setting-up of a new vial of ISE Reference Solution or of ISE Diluent then every 4 hours when quality control results fall outside the established range, after replacing electrode, and after ISE cleaning and maintenance

d. Detection limit:

Detection limit is based on linearity study performed above. In addition, method comparison study also supports the low end measuring claims of 10.8 mEq/L.

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The sponsor's claimed measuring range of the device is 10.8 – 43.0 mEq/L

e. Analytical specificity:

An endogenous interfering substances study was performed according to the CLSI EP7-A guideline. Serum samples containing the analyte at two levels (low and high) of the test were spiked with the potentially interfering substance unconjugated bilirubin, conjugated bilirubin, turbidity, ascorbic acid, hemoglobin and acetylsalicylate to several concentrations. Samples were then run in triplicate using the ProM analyzer. The recovery of the test at each concentration of interferents was calculated by comparing the mean result of testing with no interferents to the mean result at each level tested. The sponsor defines non-significant interference as bias < 10% between the spiked and unspiked samples. The highest level tested with no significant interference is listed in the table below.

| Interferents | Highest level tested with no interference |
| --- | --- |
| Turbidity | 614 mg/dL |
| Unconjugated bilirubin | 30.0 mg/dL, (513 μmol/L) |
| Conjugated bilirubin | 29.5 mg/dL, (504 μmol/L) |
| Ascorbic acid | 16.0 mg/dL
Concentrations above the therapeutic levels will interfere and cause erroneous results |
| Acetylsalicylic acid | 40 mg/dL.
Concentrations above the therapeutic levels will interfere and cause erroneous results |
| Hemoglobin | 300 mg/dL |

f. Assay cut-off:

Not applicable

2. Comparison studies:

a. Method comparison with predicate device:

A method comparison study was performed between the predicate device (ROCHE CO2-L reagent) on a cobas c111 analyzer and the candidate device (Elitech Clinical Systems CO₂) on a Selectra ProM according to the CLSI guideline EP9-A2. This study was performed using 99 serum patient samples (including 5 spiked and 3 diluted samples) and over a span of 5 days.

Regression analysis of the results yielded the following:

$$
y = 0.908 x + 2.2 \text{ mEq/L}
$$

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r = 0.985
r² = 0.970
Standard error of the estimate Sy.x = 1.3 mEq/L.
Sample range tested from 11.1 to 42.9 mEq/L

b. Matrix comparison:
40 paired serum and plasma (lithium heparin) samples, ranging from 11.7 to 39.7 mEq/L (including 2 spiked and 2 diluted), were tested on Selectra ProM according to the CLSI guideline EP9-A2.

Regression analysis of the results yielded the following:
y = 0.973 x - 0.1 mEq/L
r = 0.995
r² = 0.991
Standard error of the estimate Sy.x = 0.9 mEq/L.

The sponsor claimed that lithium heparin is an acceptable anticoagulant to be used with the CO2 assay.

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):
Not applicable

4. Clinical cut-off:
Not applicable

5. Expected values/Reference range:
Total CO2: 22-29 mEq/L for both serum and plasma

It is recommended each laboratory establishes and maintains its own reference values. The data given here are only for information.
Wu, A.H.B., Tietz Clinical guide to laboratory test, 4th Ed., (W.B. Saunders Company), (2006), 214, 234, 880, 992.

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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.