The GenChem Creatinine Test Reagent System is intended for the quantitative determination of creatinine in serum, plasma and urine on the Beckman SYNCHRON CX3® System and as an aid in the diagnosis of renal impairment and diseases such as chronic glomerulonephritis, diabetic nephropathy, chronic interstitial nephritis and as an indicator of glomerular filtration rate.

Device Description

The Device is a Reagent containing alkaline picrate for the determination of creatinine for optimum system operation on the Beckman Synchron CX3® System.

AI/ML Overview

Here's an analysis of the provided text regarding the GenChem Creatinine Test Reagent, structured to address your specific questions.

It's important to note that this document is a 510(k) Summary for an in vitro diagnostic (IVD) reagent, not an AI/ML device. Therefore, many of your questions related to AI-specific aspects (such as ground truth establishment by experts, adjudication methods, MRMC studies, training set, etc.) are not applicable to this type of submission. The performance criteria for IVDs typically revolve around analytical performance characteristics.

Acceptance Criteria and Device Performance for GenChem Creatinine Test Reagent

1. Table of Acceptance Criteria and Reported Device Performance:

Performance Characteristic	Acceptance Criteria (Implicit from Predicate)**	Reported Device Performance
Precision/Reproducibility	Comparable to predicate device (Beckman Creatinine Reagent for the CX3) and acceptable for clinical use.	Serum 1: Mean 0.5 mg/dL, Within Run SD 0.05, %CV 9.8, Total SD 0.05, %CV 9.8 Serum 2: Mean 4.0 mg/dL, Within Run SD 0.02, %CV 0.5, Total SD 0.02, %CV 0.5 Serum 3: Mean 7.4 mg/dL, Within Run SD 0.03, %CV 0.5, Total SD 0.05, %CV 0.7 Urine 1: Mean 40.3 mg/dL, Within Run SD 0.41, %CV 1.0, Total SD 0.56, %CV 1.4 Urine 2: Mean 222.9 mg/dL, Within Run SD 2.29, %CV 1.0, Total SD 2.79, %CV 1.3
Linearity/Reportable Range	Demonstrates linearity across the clinical range and comparable to predicate.	Slope 0.994, Intercept -0.05, Standard Error of Estimate 0.11, r = 1.00 Serum/Plasma: 0.2 to 25 mg/dL Urine: 10 to 400 mg/dL
Sensitivity	Detects creatinine at clinically relevant low levels.	0.2 mg/dL (claimed limit), observed sensitivity 0.01 mg/dL (lower is better)
Analytical Specificity (Interference)	No significant interference from common exogenous or endogenous substances at tested concentrations.	No adverse effect on 1.1 mg/dL creatinine sample from: Hemoglobin up to 500 mg/dL Bilirubin up to 20 mg/dL Lipemia up to 1800 mg/dL
Method Comparison (Patient Samples)	Results compare favorably with the predicate device on patient samples, demonstrating substantial equivalence.	Serum: Intercept 0.0, Slope 0.991, R2 0.997 (N=80, Range 0.4 - 30.4 mg/dL) Plasma: Intercept 0.05, Slope 0.998, R2 0.998 (N=80, Range 0.4 - 30.4 mg/dL) Urine: Intercept -0.3, Slope 1.000, R2 1.000 (N=79, Range 12.1 - 400 mg/dL)

Notes on Acceptance Criteria:

For IVD devices seeking 510(k) clearance, the primary acceptance criterion is substantial equivalence to a legally marketed predicate device. This means the new device must perform as well as or better than the predicate, or perform similarly without raising new questions of safety or effectiveness.
The document implies that the "acceptance criteria" for each performance characteristic were that the results should be consistent with the expected performance for a creatinine assay and demonstrate equivalence to the predicate device (Beckman Creatinine Reagent for the CX3). Specific numeric acceptance thresholds are not explicitly stated as they might be for a novel device, but rather implied by the successful comparison to the predicate.

2. Sample Size Used for the Test Set and Data Provenance:

Precision/Reproducibility:
- Serum samples: 60 data points each for Serum 1, Serum 2, Serum 3 (assayed twice per day in triplicate over 10 days).
- Urine samples: 59 data points for Urine 1, 60 data points for Urine 2 (assayed twice per day in triplicate over 10 days).
- Data Provenance: Not explicitly stated, but likely from laboratory-prepared control sera/urine pools. This would be considered retrospective in the sense that the controls were pre-defined, but the testing was prospective.
Linearity: Commercially available linearity standards (0 to 25.7 mg/dl) analyzed in triplicate. Not specified how many distinct standards were used beyond the range.
Sensitivity: A diluted serum control was used, with 21 replicates for the within-run precision study.
Analytical Specificity: Stock samples with 1.1 mg/dL creatinine were tested. Not specified how many replicates or distinct samples.
Patient Comparison:
- Serum: 80 patient samples (ranging from 0.4 to 30.4 mg/dl).
- Plasma: 80 patient samples (ranging from 0.4 to 30.4 mg/dl).
- Urine: 79 patient samples (ranging from 12.1 to 400 mg/dL).
- Data Provenance: "collected from adult patients." This would be considered prospective data collection for the method comparison study. Country of origin is not specified but presumed to be the USA, given the FDA submission.

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

Not Applicable. This is an in vitro diagnostic (IVD) reagent for chemical analysis, not an AI/ML device that requires expert human interpretation of images or other subjective data to establish ground truth. The "ground truth" for an IVD device's performance is established by the analytical method (e.g., using known concentrations in linearity standards, measuring against a reference standard in patient comparison studies using a legally marketed predicate device).

4. Adjudication Method for the Test Set:

Not Applicable. See explanation in point 3. Adjudication is typically used to resolve discrepancies in human expert interpretations, which is not relevant for this type of device.

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 not an AI-assisted diagnostic device.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done:

Not Applicable. This is an IVD reagent, not an algorithm. The device is the reagent; its performance is in its chemical reaction and subsequent detection, which is inherently "standalone" in its analytical function (meaning it provides a result without human interpretation of the underlying chemistry).

7. The Type of Ground Truth Used:

Analytical Reference/Comparative Method:
- Precision: Statistical calculations (SD, %CV) from repeated measurements of control materials with known or expected values.
- Linearity/Sensitivity: Measurements against commercially available linearity standards or diluted controls with known concentrations.
- Analytical Specificity: Measurements of samples spiked with known interferents against an unspiked control sample.
- Patient Comparison: The "ground truth" in this context is the result obtained from the predicate device (Beckman Creatinine Reagent on the SYNCHRON CX3® System). The study aimed to show that the GenChem reagent produced results that were statistically equivalent to those produced by the predicate device when testing the same patient samples.

8. The Sample Size for the Training Set:

Not Applicable. This is not an AI/ML device that requires a training set. The "development" of the reagent would involve chemical formulation and optimization, not machine learning training.

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

Not Applicable. See explanation in point 8.

Summary

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DEC 27 2004

510(k) SUMMARY K040976

1.0 Submitted Bv:

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:
3.2 21 CFR § 862.1225, Creatinine, Alkaline Picrate, Colorimetry Reagent for Beckman Synchron CX3® System
3.3 Clasification : Class II
3.4 Product Code: CGX
3.5 Panel: Clinical Chemistry (75)

4.0 Device Description:

The Device is a Reagent containing alkaline picrate for the determination of creatinine for optimum system operation on the Beckman Synchron CX3® System.

5.0 Substantial Equivalence Information:

a. Predicate Device Name: Beckman Creatinine Reagent for the CX3
b. Predicate K Number: K915077
c. Comparison with Predicate: Both Reagents are similar in design, function and chemical principle as well as ingredient composition and concentration.

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

6.1 Precision/Reproducibility:

Control sera and urine pools were each assayed twice per day in triplicate on a SYNCHRON CX3® System. Data were collected on ten different days over a thirty day

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period. Estimates of within run and total imprecision were calculated as described in NCCLS publication EP3-T.

Precision of Creatinine Recoveries (mg/dL)

Sample	n	Within Runmean SD %CV	TotalSD	%CV
Serum 1	60	0.5 0.05 9.8	0.05	9.8
Serum 2	60	4.0 0.02 0.5	0.02	0.5
Serum 3	60	7.4 0.03 0.5	0.05	0.7
Urine 1	59	40.3 0.41 1.0	0.56	1.4
Urine 2	60	222.9 2.29 1.0	2.79	1.3

Precision of Creatinine Recoveries (mg/dl )

6.2 Linearity/assay reportable range:

Linearity was performed according to NCCLS Guideline EP6-A. Commercially available linearity standards ranging from 0 to 25.7 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 0.994 with an intercept of -0.05, a standard error of estimate of 0.11 and r = 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	Conventional Units	SI Units
Serum/Plasma	0.2 to 25 mg/dL	0.2 - 2210 mmol/L
Urine	10 - 400 mg/dL	0.88 - 35.36 mmol/L

SENSITIVITY: 6.3

The sensitivity of this method is 0.2 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 0.01 mg/dL and is below the claimed limit of 0.2 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 creatinne level of 1.1 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 and plasma, ranging from 0.4 to 30.4 mg/dl and urine specimens ranging from 12.1to 400 mg/dL were collected from adult patients and assayed for creatinine on a SYNCHRON CX3® System using GenChem and Beckman creatinine reagents. Results were compared by least squares linear regression and the following statistics were obtained:

VALUE	SERUM	PLASMA	URINE
Intercept	0.0	0.05	-0.3
Slope	0.991	0.998	1.000
R2 Value	0.997	0.998	1.000
N	80	80	79
Range	0.4 - 30.4	0.4 - 30.4	12.1 – 400 mg/dl

8.0 Expected Values

The expected values for creatinine 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	0.6 - 1.3 mg/dL	53 - 115 mmol/L
Urine	11 - 26 mg/day/kg	97 - 230 mmol/day/kg

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Image /page/3/Picture/1 description: The image shows the logo for the Department of Health & Human Services-USA. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES-USA" around the perimeter. Inside the circle is a stylized image of a caduceus, which is a symbol of medicine.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

DEC 27 2004

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

Re: K040976

Trade/Device Name: GenChem Creatinine Test Reagent Regulation Number: 21 CFR 862.1225 Regulation Name: Creatinine test system Regulatory Class: Class II Product Code: CGX 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. Parks

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: K040976

Device Name: GenChem Creatinine Test Reagent

Indications For Use:

Division Sign-Off

Office of In Vitro Diag Device Evaluation an

5100k K040976

Prescription Use X

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

AND/OR

IF NEEDED)

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

Regulation Number and Section

§ 862.1225 Creatinine test system.

(a)
Identification. A creatinine test system is a device intended to measure creatinine levels in plasma and urine. Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.(b)
Classification. Class II.