The BUN Reagent is to be used for the quantitative determination of urea nitrogen in serum, plasma and urine on the Beckman SYNCHRON CX3® System to aid in the diagnosis of renal function and pre renal disease states, such as cardiac decompensation and others.

Device Description

The Device is a reagent containing sufficient Urease, surfactants and other ingredients necessary for optimum system operation on the Beckman Synchron CX3® Analyzer.

AI/ML Overview

Acceptance Criteria and Device Performance Study for GenChem, Inc. BUN Reagent

This document outlines the acceptance criteria and the results of a study demonstrating the performance of the GenChem, Inc. Electrode, Ion Specific, Urea Nitrogen (BUN) Reagent (K040973).

1. Table of Acceptance Criteria and Reported Device Performance

Performance Characteristic	Acceptance Criteria (Implicit)	Reported Device Performance
Precision/Reproducibility	Based on NCCLS EP3-T guidelines; generally low %CV for various BUN levels.	Serum 1 (7.1 mg/dL): Within Run %CV = 9.1%, Total %CV = 9.4%Serum 2 (35.4 mg/dL): Within Run %CV = 1.8%, Total %CV = 1.9%Serum 3 (63.8 mg/dL): Within Run %CV = 0.8%, Total %CV = 1.3%Urine 1 (21.7 mg/dL): Within Run %CV = 4.1%, Total %CV = 3.8%Urine 2 (112.2 mg/dL): Within Run %CV = 0.7%, Total %CV = 1.1%
Linearity/Reportable Range	Demonstrates linearity across the stated analytical range with a high correlation coefficient and low intercept/slope deviation from ideal.	Slope = 0.995, Intercept = -0.12, Standard Error of Estimate = 0.49, r² = 1.00Analytical Range: 2 - 150 mgN/dL (Normal); 150 - 300 mgN/dL (ORDAC*)
Sensitivity	Observed sensitivity limit to be ≤ claimed limit.	Claimed Limit = 2 mg/dLObserved Sensitivity Limit (3 SD) = 1.43 mg/dL
Analytical Specificity	No adverse effect from common interferents at specified concentrations.	Hemoglobin (up to 500 mg/dL), Bilirubin (up to 20 mg/dL), Lipemia (up to 1800 mg/dL) showed no adverse effect on 15 mg/dL BUN sample.
Method Comparison (Correlates with Predicate Device)	Strong correlation with the predicate device across the analytical range, indicated by high R² value, slope close to 1, and intercept close to 0.	Serum (N=80): Intercept = -0.3, Slope = 0.995, R² = 0.999Plasma (N=80): Intercept = -0.2, Slope = 0.989, R² = 0.998Urine (N=79): Intercept = 0.9, Slope = 0.979, R² = 1.000

*ORDAC: Off-Range Dilution and Concentration

2. Sample Size and Data Provenance (Test Set)

Precision/Reproducibility:
- Sample Size: 60 replicates for each of 5 samples (3 serum, 2 urine) (N=60 for each sample type). Assayed twice per day in triplicate on 10 different days over a 30-day period.
- Data Provenance: Not explicitly stated, but likely from laboratory controlled samples (control sera, diluted urine pools). This is typically a retrospective analysis of controlled lab materials.
Linearity/Assay Reportable Range:
- Sample Size: Analyzed 7 commercially available linearity standards ranging from 0 to 158 mg/dL in triplicate.
- Data Provenance: Commercially available linearity standards, typically retrospective analysis in a controlled lab setting.
Sensitivity:
- Sample Size: 21 replicates of a diluted serum control.
- Data Provenance: Diluted serum control, typically retrospective analysis in a controlled lab setting.
Analytical Specificity:
- Sample Size: Not explicitly stated as a numerical sample size but involved testing stock samples with varying concentrations of interferents (Hemoglobin, Bilirubin, Lipemia) against a base pool.
- Data Provenance: Laboratory-prepared stock solutions and base pool, typically retrospective analysis in a controlled lab setting.
Patient Comparison (Method Comparison):
- Sample Size: 80 serum specimens, 80 plasma specimens, and 79 urine specimens.
- Data Provenance: "Collected from adult patients." This indicates prospective or retrospective patient sample collection, but the context generally implies real patient samples that were de-identified and used for the study. The country of origin is not specified.

3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications

The studies described in the provided text are for an in vitro diagnostic reagent and system. For such devices, "ground truth" is typically established by comparative analysis with a well-characterized reference method or a legally marketed predicate device, rather than expert interpretation of images or clinical data.

For Precision, Linearity, Sensitivity, and Analytical Specificity: Ground truth is established by the inherent properties of the reference materials used (e.g., certified control sera, linearity standards with known concentrations) or by accepted laboratory analytical methods. No external "experts" (like radiologists) are involved in establishing this type of ground truth.
For Patient Comparison: The "ground truth" for the test set (GenChem BUN reagent) is the measurement obtained from the predicate device (Beckman BUN reagent for the CX3). The "experts" in this context would be the skilled laboratory technicians operating the instruments, but their role is to accurately perform the assays, not to interpret an uncertain "ground truth."

4. Adjudication Method for the Test Set

Adjudication methods like 2+1 or 3+1 are typically used in studies where subjective interpretation (e.g., imaging reads) is involved and discrepancies between readers need to be resolved. For an IVD reagent, data is quantitative and is compared statistically. Therefore, no adjudication method as typically understood in image-based studies was used. The comparison was a direct statistical correlation between the test device and the predicate device's quantitative results.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not performed. This type of study is relevant for diagnostic devices that involve human interpretation of results (e.g., radiologists reading images and improved performance with AI assistance). The GenChem BUN Reagent is an automated in vitro diagnostic assay where the output is a quantitative value, not subject to human interpretation in the same way. Therefore, the concept of "human readers improve with AI vs without AI assistance" does not apply here.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance)

Yes, all performance studies described are essentially standalone performance studies for the reagent on the Beckman CX3® Synchron Analyzer. The analytical performance characteristics (Precision, Linearity, Sensitivity, Analytical Specificity, and Method Comparison) measure the reagent's performance as an "algorithm only" (in the sense of an automated test system yielding a quantitative result without direct human interpretation influencing the result itself). The human "in the loop" would be operating the instrument and performing quality control, but not providing an interpretation that the algorithm augments or replaces.

7. Type of Ground Truth Used

The primary ground truth used for the method comparison study (patient comparison) was the predicate device's measurement (Beckman BUN reagent for the CX3). For other performance characteristics like precision, linearity, and sensitivity, the ground truth was established by reference materials, certified standards, or accepted laboratory methods (e.g., known concentrations of linearity standards, the mean value for precision calculations). This is synonymous with a form of expert consensus if the reference methods are considered the established gold standard.

8. Sample Size for the Training Set

The provided documentation describes performance studies for regulatory submission (510(k)). These are analytical validation studies, not machine learning model development. Therefore, there is no explicit "training set" in the context of an AI/ML algorithm. The "training" in this context refers to the development and optimization of the reagent and its methods, which would typically be done by the manufacturer through various iterations using proprietary internal samples and methodologies, but these are not disclosed as a "training set" in a regulatory submission for an IVD reagent.

9. How the Ground Truth for the Training Set Was Established

As there is no "training set" in the context of an AI/ML algorithm, this question is not applicable. The development of chemical reagents and analytical methods for IVD devices involves extensive R&D and optimization, where "ground truth" is established against known chemical properties, reference methods, and clinical needs during the development phase.

Summary

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DEC 27 2004

510(k) SUMMARY K040973

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

June 1, 2004 2.0 Date of Preparation:

3.0 Regulatory Information:

3.1 Regulation section:
3.2 21 CFR § 862.1770, Electrode, Ion Specific, Urea Nitrogen for Beckman Synchron CX3® System
3.3 Clasification : Class II
Product Code: CDS 3.4
3.5 Panel: Clinical Chemistry (75)

4.0 Device Description:

The Device is a reagent containing sufficient Urease, surfactants and other ingredients necessary for optimum system operation on the Beckman Synchron CX3® Analyzer.

5.0 Substantial Equivalence Information:

Predicate Device Name: a.
b.

Beckman BUN reagent for the CX3.

c. Predicate K number:

K761061.

Comparison with predicate: The two products have the same intended use, C. utilize the conductivity reactions on the same instrument, have the same analytical range, have the same stability

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

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Precision/Reproducibility: 6.1

Control sera and diluted urine pools were each assaved twice per day in triplicate on a SYNCHRON CX3® System. Data were collected on ten different days over a thirty day period. Estimates of within run and total imprecision were calculated analogous to the method in NCCLS publication EP3-T.

Sample	n	mean	Within Run		Total Imprecision
			1SD	%CV	1SD	%CV
Serum 1	60	7.1	0.65	9.1	0.66	9.4
Serum 2	60	35.4	0.62	1.8	0.66	1.9
Serum 3	60	63.8	0.50	0.8	0.80	1.3
Urine 1	60	21.7	0.89	4.1	0.82	3.8
Urine 2	60	112.2	0.75	0.7	1.25	1.1

Precision of BUN Recoveries in (maN/dL)

6.2 Linearity/assay reportable range:

Linearity was performed according to NCCLS Guideline EP6-A. Commercially available linearity standards ranging from 0 to 158 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 0.995 with an intercept of -0.12, a standard error of estimate of 0.49 and re = 1.00 and is shown below. Specimens exceeding these limits should be diluted with normal saline and reanalyzed. Multiply the result by the appropriate dilution factor.

Specimens	Range	Conventional Units	SI Units
All	Normal	2 - 150 mgN/dL	2-53.6mmol/L
All	ORDAC*	150 - 300 mgN/dL	53-107.2mmol/L

6.3 SENSITIVITY:

The sensitivity of this method is 2 mg/dL and is 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 1.43 mg/dL and is below the claimed limit of 2 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 BUN level of 15 mg/dL. Stock solutions

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

7.0 Patient Comparison

Serum and plasma specimens, and urine specimens diluted with 9 parts normal saline, ranging from 4 to 300 mg/dL were collected from adult patients and assayed for urea nitrogen on a SYNCHRON CX3® System using GenChem and Beckman BUN reagents. Results were compared by least squares linear regression and the following statistics were obtained:

VALUE	SERUM	PLASMA	URINE
Intercept	-0.3	-0.2	0.9
Slope	0.995	0.989	0.979
R2 Value	0.999	0.998	1.000
N	80	80	79
Range	4-300	4-300	6-142

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Image /page/3/Picture/1 description: The image shows the seal of the U.S. Department of Health and Human Services. The seal features a stylized caduceus, a symbol often associated with medicine and healthcare. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" are arranged in a circular pattern around the caduceus. The seal is simple and monochromatic.

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: K040973

Trade/Device Name: Electrode, Ion Specific, Urea Nitrogen (BUN) Reagent Regulation Number: 21 CFR 862.1770 Regulation Name: Urea nitrogen test system Regulatory Class: Class II Product Code: CDS 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 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: K040973

Device Name: Electrode, Ion Specific, Urea Nitrogen (BUN) Reagent

Indications For Use:

Alberto Salsi

Office of In Vitro Diagnost Device Evaluation an

510k K040973

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)

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

Regulation Number and Section

§ 862.1770 Urea nitrogen test system.

(a)
Identification. A urea nitrogen test system is a device intended to measure urea nitrogen (an end-product of nitrogen metabolism) in whole blood, serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of certain renal and metabolic diseases.(b)
Classification. Class II.