GENCHEM ISE ELECTROLYTE REFERENCE

K040971 · Genchem, Inc. · JGS · Dec 22, 2004 · Clinical Chemistry

Device Facts

• Record ID: K040971
• Device Name: GENCHEM ISE ELECTROLYTE REFERENCE
• Applicant: Genchem, Inc.
• Product Code: JGS · Clinical Chemistry
• Decision Date: Dec 22, 2004
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1665
• Device Class: Class 2

Intended Use

GenChem ISE Electrolyte Reference, when used in conjunction with the GenChem ISE Electrolyte Buffer. GenChem CO2 Acid Reagent, GenChem CO2 Alkaline Buffer, GenChem Wash Concentrate, and appropriate Calibration Standards, is intended for the quantitative determination of sodium, potassium, chloride, and total CO2 in serum and plasma, and sodium, potassium and chloride in urine, and Reference will also determine calcium in serum, plasma and urine. Sodium results are for the diagnosis and treatment of aldosteronism (excessive secretion of the hormone aldosterone), diabetes insipidus (chronic excretion of large amounts of dilute urine, accompanied by extreme thirst), adrenal hypertension, Addison's disease (caused by the destruction of the adrenal glands), dehvdration, inappropriate antidiuretic hormone secretion, or other diseases involving electrolyte imbalance. Potassium results are used to monitor electrolyte imbalance in the diagnosis and treatment of diseases and conditions characterized by low or high blood potassium levels. Chloride results are used in the treatment of electrolyte and metabolic disorders such as cystic fibrosis and diabetic acidosis. Carbon dioxide results are used in the diagnosis and treatment of numerous and potentially serious disorders associated with changes in the body's acid-base balance. Calcium results are used in the diagnosis and treatment of parathyroid diseases, chronic renal disease and tetany (intermittent muscular contractions or spasm).

Device Story

GenChem ISE Electrolyte Reference is a liquid reagent kit used with Beckman SYNCHRON CX DELTA systems to measure electrolytes (Na, K, Cl, CO2, Ca) in clinical samples. The device uses ion-selective electrodes (ISE) to generate potentials proportional to analyte activity, calculated via the Nernst equation. For CO2, the sample is acidified to convert bicarbonate to CO2 gas, which diffuses through a silicone membrane to a pH-sensitive electrode; the rate of pH change is proportional to total CO2. Used in clinical laboratories by technicians to provide quantitative results for diagnosing electrolyte imbalances, acid-base disorders, and renal/parathyroid conditions. The output assists clinicians in monitoring patient metabolic status and guiding treatment decisions.

Clinical Evidence

Bench testing only. Precision/reproducibility evaluated per NCCLS EP5-A (N=60). Linearity evaluated per NCCLS EP6-A using Least Squares method (R2=1.000 for all analytes). Sensitivity (Limit of Detection) established for all analytes. Analytical specificity evaluated per NCCLS EP7-A for hemoglobin, bilirubin, and lipemia interference. Patient comparison study (N=44-80 per analyte/specimen type) performed against Beckman reagents using least squares linear regression; results showed high correlation (r=0.935-1.000).

Technological Characteristics

Liquid reagent kit containing sodium, potassium, chloride, total CO2, calcium, surfactants, and preservatives. Operates via potentiometric ion-selective electrodes (ISE) and pCO2 electrode. Energy source provided by the host Beckman SYNCHRON CX DELTA system. Storage at room temperature. No software algorithm details provided; system relies on standard Nernst equation-based potentiometric measurement.

Indications for Use

Indicated for quantitative determination of sodium, potassium, chloride, total CO2, and calcium in serum, plasma, urine, and cerebrospinal fluid (CSF) for patients requiring electrolyte monitoring or diagnosis of metabolic/electrolyte disorders, including aldosteronism, diabetes insipidus, hypertension, Addison’s disease, cystic fibrosis, diabetic acidosis, parathyroid disease, and renal disease.

Regulatory Classification

Identification

A sodium test system is a device intended to measure sodium in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of aldosteronism (excessive secretion of the hormone aldosterone), diabetes insipidus (chronic excretion of large amounts of dilute urine, accompanied by extreme thirst), adrenal hypertension, Addison's disease (caused by destruction of the adrenal glands), dehydration, inappropriate antidiuretic hormone secretion, or other diseases involving electrolyte imbalance.

Predicate Devices

• Hi Chem Electrolyte Reference Reagent (k925611)

Submission Summary (Full Text)

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# DEC 22 2004

# 510(k) SUMMARY K040971

### 1.0 Submitted By:

C.C. Allain, Ph.D. Chief Scientific Officer GenChem. Inc. 471 W. Lambert Road, Ste 107 Brea, CA 92821 Telephone: [phone] FAX: [phone]

#### 2.0 Date of Preparation: June 1, 2004

### 3.0 Regulatory Information:

- 3.1 Regulation section: 21 CFR § 862.1665 Electrode, Ion Specific, Sodium, Potassium, Chloride, CO2, Calcium
- 3.2 Clasification : Class II
- 3.3 Product Code: JGS
- 3.4 Panel: Clinical Chemistry (75)

### 4.0 Device Description:

Sodium, Potassium, Chloride, CO2 and Calcium are determined by the use of Ion Specific Electrodes, the conductivity of which is proportional to the concentration of electrolyte in the sample which is mixed with high ionic strength buffer using the ISE Solution as the reference.

- 5.0 a. Predicate Device Name: Electrode, Ion Specific, Sodium, Potassium, Chloride, CO2, Calcium
b. Predicate K Number: K925611

e. Comparison with Predicate: Both Reagents are similar in design, function and chemical principle as well as ingredient composition and concentration.

- 6.0 Performance Characteristics: All studies were performed on the Beckman CX3® Synchron Analyzer
- 6.1 Precision/Reproducibility: Within-Day and Day-to-Day precision was determined according to NCCLS EP5-A. Results are summarized below:

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| Within-Day; N=60 | S-1 | S-2 | S-3 | U-1 | U-2 |
|------------------|------|------|------|------|-------|
| Mean (mmol/L) | 7.1 | 35.4 | 63.8 | 21.7 | 112.2 |
| SD | 0.65 | 0.62 | 0.50 | 0.89 | 0.75 |
| %CV | 9.1 | 1.9 | 1.3 | 3.8 | 1.1 |

Day-To-Day (30 Days); N=60

| | S-1 | S-2 | S-3 | U-1 | U-2 |
|---------------|------|------|------|------|-------|
| Mean (mmol/L) | 7.1 | 35.4 | 63.8 | 21.7 | 112.2 |
| SD | 0.66 | 0.66 | 0.80 | 0.82 | 1.25 |
| %CV | 9.4 | 1.9 | 1.3 | 3.9 | 1.1 |

6.2 Linearity/assay reportable range:

> Linearity was performed according to NCCLS Guideline EP6-A. Commercially available linearity standards were analyzed in triplicate on the Beckman CX3 and the results analyzed by the Least Squares method. The results are shown below. Specimens exceeding these limits should be diluted with normal saline and reanalyzed. Multiply the result by the appropriate dilution factor.

| | Intercept | Slope | R2 | Sey | Range |
|---------|-----------|-------|-------|------|-------------------|
| Calcium | 0.34 | 0.911 | 1.000 | 0.35 | 0.8 – 14.3 mg/dL |
| Na | 2.37 | 0.968 | 1.000 | 2.61 | 0 – 200 mmol/L |
| K | -0.09 | 1.017 | 1.000 | 0.03 | 0.9 – 15.2 mmol/L |
| CL | -0.71 | 0.999 | 1.000 | 0.99 | 0 – 197 mmol/L |
| CO2 | 0.15 | 1.000 | 1.000 | 0.41 | 0 – 40 mmol/L |

The results show this method is linear as shown below:

| Calcium | 0.8 to 14.3 mg/dl |
|----------|-------------------|
| Chloride | 0 to 150 mmol/L |

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| Potassium | 0.9 to 15.2 mmol/L |
|-----------|--------------------|
| Sodium | 0 to 200 mmol/L |
| Total CO2 | 0 to 40 mmol/L |

### 6.3 SENSITIVITY:

The sensitivity of this methodology was documented through the repetitive assay of a serum control first with a known concentration and then diluting the sample until the minimum result was obtained and then run in replicates of 10 on the Beckman Synchron CX3® System. Under the conditions described, the following limits of detection were established:

### Analyte

# Limit of Detection

| Calcium | 1.5 mg/dL |
|-----------|------------|
| Sodium | 10 mmol/L |
| Potassium | 1.0 mmol/L |
| Chloride | 15 mmol/L |
| Total CO2 | 5.0 mmol/L |

- Analytical Specificity: 6.4
Determined according to NCCLS EP7-A. Hemoglobin levels up to 500 mg/dL, Bilirubin levels up to 20 mg/dL, and Lipemia levels up to 1800 mg/dL were tested and did not show any adverse effect on a stock sample with levels of sodium at 148 mmol/L, potassium at 5.2 mmol/L, chloride at 119 mmol/L, CO2 at 19 mmol/L, and calcium at 9.4 mg/dL. Stock solutions of the substance to be tested were prepared at 20x concentrations and 0.5 ml of this stock was placed in a 10 ml volumetric flask and made up to volume with the base pool. The control stock was prepared similarly but with water as the diluent. Only Sodium Heparin, Lithium Heparin and Ammonium Heparin up to 45 Units/mL are acceptable anticoagulants.

### 7.0 PATIENT COMPARISON

Serum, plasma, cerebrospinal fluid and urine specimens, collected from adult patients, were assayed for calcium, chloride, potassium, sodium, and total CO2 on a SYNCHRON CX3® System using GenChem and Beckman flow cell reagents, wash solutions and calibrators. Results were compared by least squares linear regression where X = Beckman Results and Y = GenChem Results.

> Regression Statistics Summary Statistics

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| AnalyteSpecimen | Unit | n | m | b | r | range |
|-----------------|--------|----|-------|------|-------|------------|
| Calcium | | | | | | |
| Serum | mg/dL | 80 | 0.989 | 0.0 | 0.985 | 7.1 - 10.6 |
| Plasma | mg/dL | 80 | 0.990 | 0.0 | 0.995 | 7.1 - 10.7 |
| Urine | mg/dL | 74 | 1.007 | -0.2 | 0.998 | 2.4 - 15.2 |
| Chloride | | | | | | |
| Serum | mmol/L | 80 | 0.988 | 1.0 | 0.935 | 98 - 127 |
| Plasma | mmol/L | 80 | 0.998 | 0.8 | 0.985 | 98 - 127 |
| Urine | mmol/L | 78 | 1.049 | -5.1 | 0.999 | 22 - 289 |
| CSF | mmol/L | 44 | 1.024 | -3.4 | 0.985 | 113 - 152 |
| Potassium | | | | | | |
| Serum | mmol/L | 80 | 0.969 | 0.13 | 1.000 | 3.2 - 10.8 |
| Plasma | mmol/L | 80 | 0.987 | 0.15 | 1.000 | 3.2 - 10.8 |
| Urine | mmol/L | 80 | 0.993 | 0.01 | 1.000 | 3.5 - 136 |
| Sodium | | | | | | |
| Serum | mmol/L | 80 | 0.930 | 9.1 | 0.938 | 132 - 159 |
| Urine | mmol/L | 78 | 1.000 | -0.3 | 1.000 | 17 - 288 |
| Total CO2 | | | | | | |
| Serum | mmol/L | 80 | 0.949 | 1.2 | 0.953 | 9.5 - 29 |
| Plasma | mmol/L | 80 | 0.965 | 0.9 | 0.960 | 9.5 - 29 |

8.0 Expected Values/ Reference Range:

The expected values for calcium, chloride, potassium, sodium, and total CO2 are listed below. Use these ranges only as guides. Each laboratory should establish its own reference ranges.

| Reference Ranges1<br>Analyte | Specimen | Conventional Units | SI Units |
|------------------------------|--------------|--------------------|--------------------|
| Calcium | Serum/Plasma | 8.4 - 10.2 mg/dL | 2.10 - 2.55 mmol/L |
| | Urine | 100 - 300 mg/day | 2.5 - 7.5 mmol/day |
| Chloride | Serum/Plasma | 101 - 111 mmol/L | same |
| | Urine | 110 - 250 mmol/day | same |
| | CSF | 118 - 132 mmol/L | same |
| Potassium | Serum/Plasma | 3.5 - 5.1 mmol/L | same |
| | Urine | 25 - 125 mmol/day | same |
| Sodium | Serum/Plasma | 136 - 145 mmol/L | same |
| | Urine | 40 - 220 mmol/day | same |
| Total CO2 | Serum/Plasma | 22 - 28 mmol/L | same |

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Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" arranged around the perimeter. Inside the circle is a stylized image of an eagle with three lines representing its wings.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

DEC 22 2004

C.C. Allain, Ph.D. Chief Scientific Officer GenChem, Inc. 471 W. Lambert Road, Suite 107 Brea, CA 92821

Re: k040971

Trade/Device Name: GenChem ISE Electrolyte Reference Regulation Number: 21 CFR 862.1665 Regulation Name: Sodium test system Regulatory Class: Class II · Product Code: JGS, CEM, CGZ, JFL, JFP Dated: October 15, 2004 Received: October 15, 2004

Dear Dr. Allain:

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. 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.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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 requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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# Page 2 -

This letter will allow you to begin marketing your device as described in your Section 510(k) I mo teter notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Sincerely yours,

Cornelia B. Lorke

Cornelia B. Rooks, MA Acting Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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## INDICATIONS FOR USE

510(k) Number: K040971

### Device Name: GenChem ISE Electrolyte Reference

Indications For Use:

GenChem ISE Electrolyte Reference, when used in conjunction with the GenChem ISE Electrolyte Buffer. GenChem CO2 Acid Reagent, GenChem CO2 Alkaline Buffer, GenChem Wash Concentrate, and appropriate Calibration Standards, is intended for the quantitative determination of sodium, potassium, chloride, and total CO2 in serum and plasma, and sodium, potassium and chloride in urine, and Reference will also determine calcium in serum, plasma and urine.

Sodium results are for the diagnosis and treatment of aldosteronism (excessive secretion of the hormone aldosterone), diabetes insipidus (chronic excretion of large amounts of dilute urine, accompanied by extreme thirst), adrenal hypertension, Addison's disease (caused by the destruction of the adrenal glands), dehvdration, inappropriate antidiuretic hormone secretion, or other diseases involving electrolyte imbalance. Potassium results are used to monitor electrolyte imbalance in the diagnosis and treatment of diseases and conditions characterized by low or high blood potassium levels. Chloride results are used in the treatment of electrolyte and metabolic disorders such as cystic fibrosis and diabetic acidosis. Carbon dioxide results are used in the diagnosis and treatment of numerous and potentially serious disorders associated with changes in the body's acid-base balance. Calcium results are used in the diagnosis and treatment of parathyroid diseases, chronic renal disease and tetany (intermittent muscular contractions or spasm).

Prescription Use X

AND/OR

Over-The-Counter Use

(Part 21 CFR 801 Subpart D)

(21 CFR 807 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE

IF NEEDED)

Carol C. Bensen

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

2 Millia Commento Discroostic

K04097/