GenChem Calcium Reagent is intended for the quantitative determination of total calcium in serum, plasma and urine on the Beckman SYNCHRON CX3® System to aid in the diagnosis of diseases associated with hypercalcemia and hypocalcemia.

Device Description

GenChem's Calcium reagent is a liquid composed of Arsenazo III and buffer for the quantitative determination of Calcium in serum, plasma and urine on the Beckman Synchron CX3® System.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study details for the GenChem Calcium, Azo Dye Reagent, based on the provided 510(k) summary:

Acceptance Criteria and Reported Device Performance

Criteria	Acceptance Criteria (Implied/Standard)	Reported Device Performance
Precision	Low %CV (Coefficient of Variation) for both within-run and total imprecision, indicating consistent and reproducible results across various calcium levels. Specific targets are not explicitly stated but are implicit in good laboratory practice and NCCLS standards.	Serum 1 (7.2 mg/dL): Within-run SD 0.06, %CV 0.7; Total SD 0.10, %CV 1.4Serum 2 (10.6 mg/dL): Within-run SD 0.05, %CV 0.5; Total SD 0.09, %CV 0.9Serum 3 (14.0 mg/dL): Within-run SD 0.05, %CV 0.3; Total SD 0.09, %CV 0.6Urine 1 (4.0 mg/dL): Within-run SD 0.03, %CV 0.7; Total SD 0.16, %CV 4.1Urine 2 (12.7 mg/dL): Within-run SD 0.06, %CV 0.5; Total SD 0.13, %CV 1.0
Linearity	Strong linear relationship (R-squared close to 1.0) across the claimed analytical range, with a slope close to 1 and intercept close to 0 when compared to reference or known values.	Slope: 0.911Intercept: 0.34Standard error of estimate: 0.35R-squared (r²): 1.000 (indicating excellent linearity)
Reportable Range	Defined usable range for accurate measurements.	Conventional Units: 0.1 to 15 mg/dLSI Units: 0.5 – 3.75 mmol/L
Sensitivity	Ability to detect the lowest concentration of calcium accurately. The observed sensitivity should be at or below the claimed limit.	Claimed sensitivity: 0.1 mg/dLObserved sensitivity (3 SD of 21 replicate within-run precision study): 0.05 mg/dL (which is below the claimed limit)
Analytical Specificity	No significant interference from common endogenous substances (hemoglobin, bilirubin, lipemia) or acceptable anticoagulants.	Hemoglobin: Up to 500 mg/dL showed no adverse effect.Bilirubin: Up to 20 mg/dL showed no adverse effect.Lipemia: Up to 1800 mg/dL showed no adverse effect.Acceptable Anticoagulants: Heparin, Lithium Heparin, Ammonium Heparin, EDTA.
Method Comparison	Good correlation with a legally marketed predicate device (Predicate Device Name: HICHEM Calcium Reagent for the CX3). Indicators include R-squared close to 1.0, slope close to 1, and intercept close to 0.	Serum: Intercept -0.1, Slope 0.994, R² 0.971Plasma: Intercept -0.1, Slope 0.973, R² 0.980Urine: Intercept 0.1, Slope 0.999, R² 0.999
Expected Values	Provision of reference ranges for serum/plasma and urine.	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)(Note: Stated that "Each laboratory should establish its own normal ranges.")

Study Details:

Sample sizes used for the test set and the data provenance:
- Precision:
  - 60 data points for each of 5 samples (3 serum controls, 2 urine pools). Total 300 measurements.
  - Data provenance: Not explicitly stated, but implies laboratory-prepared control sera and diluted urine pools, likely internal to GenChem or the testing facility.
- Linearity:
  - Commercially available linearity standards (0 to 15 mg/dL) analyzed in triplicate. Specific number of standards not given, but at least 2 points are needed to determine a slope.
  - Data provenance: Commercially available standards.
- Sensitivity:
  - 21 replicates of a diluted serum control.
  - Data provenance: Diluted serum control.
- Analytical Specificity:
  - Hemoglobin, Bilirubin, Lipemia (stock solutions tested with a base pool containing 9.4 mg/dL calcium). Number of samples not specified, but typically involves a few replicates for each interferent.
  - Data provenance: Prepared stock solutions and a base pool.
- Patient Comparison (Method Comparison):
  - Serum: N = 82 patient specimens
  - Plasma: N = 84 patient specimens
  - Urine: N = 76 patient specimens
  - Data provenance: "collected from adult patients." Country of origin is not specified, but the context implies it was likely from a clinical site in the US. The data is retrospective, as the samples were "collected" and then assayed.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- For Precision, Linearity, Sensitivity, Analytical Specificity: Not applicable. The "ground truth" for these tests comes from known concentrations in control materials or the inherent chemical properties of analytes and interferents.
- For Method Comparison: The ground truth is established by the results obtained from the predicate device (HICHEM Calcium Reagent for the CX3) on the Beckman CX3 Synchron Analyzer. There is no mention of human experts establishing ground truth for these quantitative measurements.
Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- Not applicable. This is a quantitative diagnostic device, not one requiring subjective interpretation that would necessitate adjudication among human readers. The performance is assessed by comparing numerical results to expected values or a predicate device.
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:
- No. This is a chemical reagent for an automated analyzer, not an AI-assisted diagnostic imaging or interpretative device. Therefore, MRMC studies and human reader improvement with AI are not relevant.
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, implicitly. The entire performance evaluation describes the standalone performance of the GenChem Calcium Reagent on the Beckman CX3® System. The test results are generated by the algorithm (reagent and instrument's measurement process) without human interpretive input affecting the quantitative result itself (though human interaction is needed for sample loading, running the test, and interpreting the final numerical value in a clinical context).
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- Precision, Linearity, Sensitivity, Analytical Specificity: Known concentrations of control materials, linearity standards, or stock solutions.
- Method Comparison: Results from a legally marketed predicate device (HICHEM Calcium Reagent for the CX3), assuming the predicate device provides accurate measurements, served as the reference for comparison.
The sample size for the training set:
- Not applicable. This device is a chemical reagent and not an AI/machine learning algorithm that requires a training set in the conventional sense. The development of such reagents relies on chemical formulation, optimization, and validation studies rather than data-driven "training."
How the ground truth for the training set was established:
- Not applicable, as there is no "training set" for this type of device.

Summary

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DEC 27 2004

510(k) SUMMARY K040972

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 § 862.1145 GenChem Calcium Reagent for the Beckman Synchron CX3 System.
3.2 Clasification : Class II
3.3 Product Code: CJY
3.4 Panel: Clinical Chemistry (75)

4.0 Device Description:

GenChem's Calcium reagent is a liquid composed of Arsenazo III and buffer for the quantitative determination of Calcium in serum, plasma and urine on the Beckman Synchron CX3® System.

5.0 Substantial Equivalence Information:

a. Predicate Device Name: HICHEM Calcium Reagent for the CX3
b. Predicate K Number: K941764

Comparison with Predicate: The two products have the same intended C. use, chemical principle, composition, analytical range and stability.

6.0 Performance Characteristics: All studies were performed on the Beckman CX3 Synchron Analyzer

6.1 Precision/Reproducibility:

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Control sera and diluted urine pools were each assayed 3 times per day over 10 days.on a SYNCHRON CX3® System. Estimates of within run and total imprecision were calculated as described in NCCLS publication EP3-T 8

Precision of Total Calcium Recoveries (mg/dL)

Sample	n	mean	SD	%CV	SD	%CV
Serum 1	60	7.2	0.06	0.7	0.10	1.4
Serum 2	60	10.6	0.05	0.5	0.09	0.9
Serum 3	60	14.0	0.05	0.3	0.09	0.6
Urine 1	60	4.0	0.03	0.7	0.16	4.1
Urine 2	60	12.7	0.06	0.5	0.13	1.0

6.2 Linearity/assay reportable range:

Linearity was performed according to NCCLS Guideline EP6-A. Commercially available linearity standards ranging from 0 to 15 mg/dL were analyzed in triplicate on the Beckman CX3® and the results analyzed by the Least Squares method. The results gave a slope of 0.911 with an intercept of 0.34, a standard error of estimate of 0.35 and r2 = 1.000. Samples exceeding these limits should be diluted with normal saline and reanalyzed. Multiply the result by the appropriate dilution factor.

		Usable Range
Specimens	Range	Conventional Units	SI Units
All	Normal	0.1 to 15 mg/dL	0.5 – 3.75 mmol/L

6.3 SENSITIVITY

The sensitivity of this method is 0.1 mg/dL and was documented through the repetitive assay of a diluted serum control. The observed sensitivity limit, calculated as three standard deviations of a 21 replicate within run precision study, is 0.05 mg/dL and is below the claimed limit of 0.1 mg/dL.

6.4 Analytical Specificity

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 a calcium level of 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.

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Heparin, Lithium Heparin Ammonium Heparin, and EDTA are acceptable anticoagulants.

7.0 Patient Comparison

Serum, plasma, and urine specimens, collected from adult patients, ranging from 0 to 15.2 mg/dL were assayed for total calcium on a SYNCHRON CX3® System using GenChem and Beckman® calcium reagents. Results were compared by least squares linear regression and the following statistics were obtained.

VALUE	SERUM	PLASMA	URINE
Intercept	-0.1	-0.1	0.1
Slope	0.994	0.973	0.999
R2 Value	0.971	0.980	0.999
N	82	84	76
Range (mg/dL)	7.0 - 10.6	7.4 - 10.5	0.4 - 15.2

8.0 Expected Values/ Reference Range:

The expected values for total calcium are listed below. Use these ranges only as guides. Each laboratory should establish its own normal ranges.

Normal Ranges

Specimens	Conventional Units	SI Units
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

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Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is a circular emblem with the department's name encircling an abstract symbol. The symbol resembles an eagle or a bird in flight, composed of three stylized human profiles facing right. The profiles are stacked vertically, creating a sense of depth and unity.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

DEC 27 2004

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

Re: K040972

Trade/Device Name: GenChem Calcium, Azo Dye Reagent Regulation Number: 21 CFR 862.1145 Regulation Name: Calcium test system Regulatory Class: Class II Product Code: CJY 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) premarket 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 vours.

Sincerely, yours,

Cornelia B. Lorks

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: K040972

Device Name: GenChem Calcium, Azo Dye Reagent

Indications For Use:

Over-The-Counter Use__________________________________________________________________________________________________________________________________________________________ AND/OR Prescription Use X (21 CFR 807 Subpart C) (Part 21 CFR 801 Subpart D) (PLEASE DO NOT WRITE BELOW THIS LINE – CONTINUE ON ANOTHER PAGE IF NEEDED)

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

Albert Satz
Division Sign-Off

Office of In Vitro Diagr Device Evaluation:

5100k K040972

Regulation Number and Section

§ 862.1145 Calcium test system.

(a)
Identification. A calcium test system is a device intended to measure the total calcium level in serum. 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).(b)
Classification. Class II.