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 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.

AI/ML Overview

The provided submission, K040971, describes the performance characteristics of the GenChem ISE Electrolyte Reference device. The studies conducted evaluate precision/reproducibility, linearity/assay reportable range, sensitivity, analytical specificity, and patient comparison.

Here's an analysis of the acceptance criteria and the studies that prove the device meets these criteria:

1. Table of Acceptance Criteria and Reported Device Performance

The submission doesn't explicitly state "acceptance criteria" as pass/fail thresholds for each performance characteristic. Instead, it presents the results of various validation studies, implying that these results are considered acceptable for demonstrating substantial equivalence to the predicate device (K925611). The predicate device comparison (Section 5.e) states, "Both Reagents are similar in design, function and chemical principle as well as ingredient composition and concentration," which suggests the performance targets are implicitly aligned with the predicate's known performance.

However, we can infer performance targets for linearity (high R² value, slope near 1, intercept near 0) and patient comparison (similar m, b, and r to predicate or acceptable clinical correlation). Let's present the reported performance.

Performance Characteristic	Analyte	Implicit Acceptance Criteria (Inferred)	Reported Device Performance
Precision/Reproducibility		Low %CV (acceptable variability)
Within-Day (N=60)	S-1		9.1% CV
	S-2		1.9% CV
	S-3		1.3% CV
	U-1		3.8% CV
	U-2		1.1% CV
Day-To-Day (N=60, 30 Days)	S-1		9.4% CV
	S-2		1.9% CV
	S-3		1.3% CV
	U-1		3.9% CV
	U-2		1.1% CV
Linearity/Reportable Range		R² close to 1, Slope close to 1, Intercept close to 0
Calcium			R²=1.000, Slope=0.911, Intercept=0.34, Range: 0.8 – 14.3 mg/dL
Na			R²=1.000, Slope=0.968, Intercept=2.37, Range: 0 – 200 mmol/L
K			R²=1.000, Slope=1.017, Intercept=-0.09, Range: 0.9 – 15.2 mmol/L
CL			R²=1.000, Slope=0.999, Intercept=-0.71, Range: 0 – 197 mmol/L
CO2			R²=1.000, Slope=1.000, Intercept=0.15, Range: 0 – 40 mmol/L
Sensitivity (Limit of Detection)		Detection limit below clinical relevance
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	All	No adverse effect from interferences	Hemoglobin (up to 500 mg/dL), Bilirubin (up to 20 mg/dL), Lipemia (up to 1800 mg/dL) had no adverse effect. Only Sodium Heparin, Lithium Heparin, and Ammonium Heparin (up to 45 Units/mL) are acceptable anticoagulants.
Patient Comparison		Strong correlation (m near 1, b near 0, r near 1) with predicate
Calcium	Serum		m=0.989, b=0.0, r=0.985
	Plasma		m=0.990, b=0.0, r=0.995
	Urine		m=1.007, b=-0.2, r=0.998
Chloride	Serum		m=0.988, b=1.0, r=0.935
	Plasma		m=0.998, b=0.8, r=0.985
	Urine		m=1.049, b=-5.1, r=0.999
	CSF		m=1.024, b=-3.4, r=0.985
Potassium	Serum		m=0.969, b=0.13, r=1.000
	Plasma		m=0.987, b=0.15, r=1.000
	Urine		m=0.993, b=0.01, r=1.000
Sodium	Serum		m=0.930, b=9.1, r=0.938
	Urine		m=1.000, b=-0.3, r=1.000
Total CO2	Serum		m=0.949, b=1.2, r=0.953
	Plasma		m=0.965, b=0.9, r=0.960

2. Sample sizes used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

Precision/Reproducibility:
- Within-Day: N=60 for each of 5 samples (S-1, S-2, S-3, U-1, U-2).
- Day-to-Day: N=60 over 30 days for each of 5 samples.
Linearity/Assay Reportable Range: Commercially available linearity standards were analyzed in triplicate. The exact number of points in the range for each analyte is not specified beyond "standards."
Sensitivity: Repetitive assay of a serum control, then diluted, run in "replicates of 10."
Analytical Specificity: Tested with varying levels of Hemoglobin, Bilirubin, and Lipemia in stock samples, and different types of Heparin. The exact N for each interference study is not explicitly stated.
Patient Comparison:
- Calcium (Serum/Plasma): 80 samples for each.
- Calcium (Urine): 74 samples.
- Chloride (Serum/Plasma): 80 samples for each.
- Chloride (Urine): 78 samples.
- Chloride (CSF): 44 samples.
- Potassium (Serum/Plasma/Urine): 80 samples for each.
- Sodium (Serum): 80 samples.
- Sodium (Urine): 78 samples.
- Total CO2 (Serum/Plasma): 80 samples for each.
Data Provenance: The document states that specimens were "collected from adult patients." There is no information regarding the country of origin of the data or whether the studies were retrospective or prospective. Given the nature of a 510(k) submission for an IVD for general clinical use, these studies are typically prospective tests on patient samples.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

This device is an In Vitro Diagnostic (IVD) for quantitative measurement of analytes. Ground truth for such devices is typically established through reference methods or established predicate devices, not by human expert interpretation.

For the Precision/Reproducibility, Linearity, Sensitivity, and Analytical Specificity studies, the "ground truth" or reference values are inherent to the controls and standards used, or are derived by diluting known concentrations.
For the Patient Comparison study, the "ground truth" is established by the results obtained from the predicate device, the Beckman CX3® Synchron Analyzer using Beckman flow cell reagents, wash solutions, and calibrators. No human experts are involved in establishing ground truth for these quantitative measurements.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

Not applicable. This is an IVD device for quantitative measurements. Clinical laboratory results are typically determined by automated analyzers or technician analysis against established assay protocols, not by expert adjudication as seen in image analysis or pathology studies.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

Not applicable. This is an In Vitro Diagnostic (IVD) device for quantitative chemical analysis, not an AI-assisted diagnostic imaging or interpretation system involving human readers.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

Yes, directly. The entire performance evaluation focuses on the standalone performance of the GenChem ISE Electrolyte Reference device (reagents) when run on the Beckman CX3® Synchron Analyzer. The reported results for precision, linearity, sensitivity, analytical specificity, and patient comparison reflect the inherent performance of the device itself. There is no human-in-the-loop component being evaluated in the context of improving performance.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

The ground truth used for performance evaluation is primarily:

Reference standards and controls: For precision, linearity, sensitivity.
Predicate device results: For patient comparison, the results from the Beckman CX3 employing the Beckman reagents serve as the comparative "ground truth" to demonstrate substantial equivalence.

8. The sample size for the training set

Not applicable. This is a traditional IVD device (reagent for an analyzer), not a machine learning or AI-driven algorithm that requires a "training set" in the computational sense. The device's performance is based on its chemical and electrical properties and calibration against known standards.

9. How the ground truth for the training set was established

Not applicable, as there is no "training set" in the context of an AI/ML algorithm. Calibration and validation are instead performed using:

Commercially available linearity standards with known concentrations (for linearity).
Serum controls with known concentrations (for sensitivity).
Reference materials for establishing the validity of the testing performed (implicitly for methods like NCCLS EP5-A, EP6-A, EP7-A).

Summary

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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: (714) 529-7125 FAX: (714) 529-3339

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:

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 Ranges1Analyte	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 (301) 594-3084. 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 (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

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:

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/

Regulation Number and Section

§ 862.1665 Sodium test system.

(a)
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.(b)
Classification. Class II.