Diazyme Creatinine Liquid Reagents Assay, in conjunction with Diazyme Creatinine Calibrator, is intended for the quantitative determination of creatinine in serum 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. For in vitro diagnostic use only.

Diazyme Creatinine Control is an assayed QC material for use in quantitative in vitro diagnostic determination of creatinine in human serum and urine. It is intended as a reference sample for monitoring the Diazyme Creatinine Liquid Reagents Assay for gross systematic errors. For in vitro diagnostic use only.

Device Description

This enzymatic assay for creatinine involves a series of coupled enzymatic reactions including creatininase enzymatic conversion of creatinine into the product creatine. which itself is converted to sarcosine by creatine amidinohydrolase (creatinase), followed by oxidation of sarcosine by sarcosine oxidase (SOD) producing hydrogen peroxide. In the presence of peroxidase (POD) the hydrogen peroxide is quantified at 550mm by the formation of a colored dye.

AI/ML Overview

Here's an analysis of the Diazyme Creatinine Assay based on the provided 510(k) summary, structured to address your specific questions:

Device: Diazyme Creatinine Liquid Reagents Assay

Acceptance Criteria and Reported Device Performance

The acceptance criteria are implied by the comparison to the predicate device, Roche Creatinine Plus (K003261). The study aims to demonstrate substantial equivalence, meaning its performance characteristics should be similar to or better than the predicate's.

Performance Characteristic	Predicate Device (Roche Creatinine Plus) Criteria/Performance	Diazyme Creatinine Liquid Reagents Assay Performance	Conclusion (Equivalency)
Recovery	Average of 105.0%	Average of 102.6% (Analytical recoveries for 11 serum samples: 97.8% - 109.4%; for 22 urine samples: 97.0% - 104.3%)	Similar
Reportable Range (Serum)	2.7 - 2652 µmol/L	0.14 - 13.56 mg/dL (12 - 1200 µmol/L)	Not explicitly stated as equivalent, range presented differently
Reportable Range (Urine)	27 - 35360 µmol/L	0.14 - 141.25 mg/dL (12 - 12500 µmol/L)	Not explicitly stated as equivalent, range presented differently
Precision/Serum (Within Run)	0.7% - 0.9%	0.1% - 2.1% (Values provided for various concentrations)	Similar
Precision/Serum (Total)	1.6% - 2.5%	1.4% - 3.0% (Values provided for various concentrations)	Similar
Precision/Urine (Within Run)	0.8% - 1.0%	0.31% - 0.46% (Values provided for various concentrations)	Similar
Precision/Urine (Total)	2.1% - 3.7%	0.61% - 2.64% (Values provided for various concentrations)	Similar
Accuracy/Serum (Correlation Coefficient)	0.999	0.9981 (Study states "0.99 for both serum samples")	Similar
Accuracy/Serum (Slope/Intercept)	y = 0.989x + 0.036	y = 0.9467x + 0.0643	Similar
Accuracy/Urine (Correlation Coefficient)	0.999	0.9969 (Study states "0.99 for both urine samples")	Similar
Accuracy/Urine (Slope/Intercept)	y = 0.999x + 0.037	y = 1.005x - 0.2979	Similar

The "Equivalency" column in the original document is based on a direct comparison of characteristics, essentially serving as a statement of acceptance criteria by the submitter. The document explicitly states: "The minor differences in the performances of the tests should not affect the safety and effectiveness of the Diazyme Creatinine Liquid Reagents Assay and offers users a rapid device to measure creatinine in human serum."

1. Sample sizes used for the test set and the data provenance:

Accuracy/Recovery Studies:
- Serum samples: 11 samples were used for analytical recovery.
- Urine samples: 22 samples were used for analytical recovery.
Interference studies: "Pooled human serum and urine" were used for testing. Specific number of samples beyond "pooled" is not provided.
Precision studies: Not explicitly stated as "test set" samples, but these are performance characteristics based on multiple measurements of specific samples/concentrations.
- For serum: Measurements at 4 concentrations (0.75, 1.41, 3.91, 10.28 mg/dL).
- For urine: Measurements at 3 concentrations (30, 87.13, 196.70 mg/dL).
Provenance: The document ("510(k) Summary") does not specify the country of origin of the data or whether the studies were retrospective or prospective. Given that it's a pre-market submission, these performance tests are typically prospective.

2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

This device is an in vitro diagnostic (IVD) assay for measuring a specific biomarker (creatinine). The "ground truth" for such assays is established by reference measurement procedures or highly accurate predicate devices, not by expert consensus (like in image analysis).
The ground truth in this study was established using the Roche Creatinine Plus (K003261) predicate device. No human experts were involved in establishing the ground truth for the numeric values of creatinine.

3. Adjudication method for the test set:

Not applicable as this is an IVD assay where ground truth is based on a predicate device or reference method, not human interpretation.

4. 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/CAD (Computer-Aided Detection) device meant to assist human readers. It's a standalone in vitro diagnostic assay.

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

Yes, this was a standalone performance study. The Diazyme Creatinine Liquid Reagents Assay's performance (accuracy, precision, recovery, reportable range, interference) was evaluated as a standalone product and compared directly to the predicate device's performance. There is no human-in-the-loop component for this type of chemical assay.

6. The type of ground truth used:

The ground truth was established by comparison to a legally marketed predicate device (Roche Creatinine Plus, K003261). This is a common and accepted method for demonstrating substantial equivalence for IVD devices, where the predicate serves as the "truth" for comparison. The predicate itself would have been validated against a reference method (e.g., isotope dilution mass spectrometry (IDMS) or other highly accurate chemical methods).

7. The sample size for the training set:

Not applicable in the typical sense for machine learning/AI. This is a chemical assay, not an algorithm that requires a "training set" to learn. The assay relies on established biochemical reactions and calibration. The "training" in this context would refer to internal analytical validation and optimization during the assay development process, not a distinct medical data training set for a "model."

8. How the ground truth for the training set was established:

Not applicable. As explained above, there isn't a "training set" for this type of chemical assay. The system is calibrated, and its ground truth for evaluation is the predicate device's results.

Summary

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Kol62105

Pre-market Notification Diazyme Creatinine Assay

510(k) Summary

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92

Submitter's name:	Diazyme Laboratories
Submitter's address:	3550 General Atomics CourtSan Diego, CA 92121USA	APR 23 2007
Name of Contact Person:	Dr Abhijit DattaDiazyme Laboratories3550 General Atomics CourtSan Diego, CA 92121Phone: 858-455-4762Fax: 858-455-2120
Date the Summary was Prepared:	Revised on March 27, 2007
Name of the Device	In Vitro Diagnostic Creatinine Test System
Trade Name:	Diazyme Creatinine Liquid Reagents AssayDiazyme Creatinine Control
Common/Usual Name	Creatinine Test System
Device Classification Name	Enzymatic Method, CreatinineSingle (specified) analyte controls (assayed and unas-sayed
Product code:	JFY, JJX
Submission Type	510k
Regulation Number	862.1225, 862.1660
Device Class	II (Enzymatic Method, Creatinine)I (Single (specified) analyte controls (assayed and unas-sayed)
Predicate Device:	For the Creatinine test system, we are claiming equiva-lence [807.92(a) (3) to CREATININE PLUS (K003261)manufactured by Roche Diagnostics GmbH, D-68298Mannheim, Germany.For the Diazyme Creatinine control which is a single(specified) analyte controls (assayed), the predicate isK063206

R 3/29/07

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Substantial Equivalence Information

1. Predicate device name(s):

Roche Creatinine Plus

Dimension Vista Protein Control L, M, H

2. Predicate 510(k) number(s):

K003261, K063206

3. Comparison with predicate:

Indications for Use

Diazyme Creatinine Liquid Reagents Assay Roche Creatinine plus test	Equivalency
Diazyme Creatinine Liquid Reagents Assay For the quantitative in vitro determinationin conjunction with Diazyme Creatinine of creatinine in human serum or urine.Calibrator, is intended for the quantitativedetermination of creatinine in serum andurine. Creatinine measurements are used inthe diagnosis and treatment of renaldiseases, in monitoring renal dialysis, and asa calculation basis for measuring other urineanalytes. For in vitro diagnostic use only.	Same

Diazyme Creatinine Liquid Reagents Assay Roche Creatinine plus test

Equivalency

Diazyme Creatinine Liquid Reagents Assay For the quantitative in vitro determinationin conjunction with Diazyme Creatinine of creatinine in human serum or urine.Calibrator, is intended for the quantitativedetermination of creatinine in serum andurine. Creatinine measurements are used inthe diagnosis and treatment of renaldiseases, in monitoring renal dialysis, and asa calculation basis for measuring other urineanalytes. For in vitro diagnostic use only.

Same

Principle

Diazyme Creatinine Liquid Reagents Assay	Roche Creatinine plus test	Equivalency
The enzymatic assay for creatinine involvesa series of coupled enzymatic reactions in-cluding creatininase enzymatic conversionof creatinine into the product creatinewhich itself is converted to sarcosine bycreatine amidinohydrolase (creatinase), fol-lowed by oxidation of sarcosine by sarco-sine oxidase (SOD), producing hydrogenperoxide. In the presence of peroxidase(POD), the hydrogen peroxide is quantifiedat 550 nm by the formation of a coloreddye. Any endogenous creatine present inthe sample is removed by creatinase andsarcosine oxidase during preincubation.	The enzymatic method is based on the es-tablished determination of sarcosine afterconversion of creatinine with the aid ofcreatininase, creatinase, and sarcosine oxi-dase. The liberated hydrogen peroxide ismeasured via a modified Trinder reaction.Endogenous creatine is metabolized withthe addition of R1 to the sample.	Same

Test Objective

Diazyme Creatinine Liquid Reagents Assay	Roche Creatinine plus test	Equivalency
For the quantitative in vitro determination of creatinine in human serum or urine.	For the quantitative in vitro determination of creatinine in human serum or urine.	Same

Type of Test

Diazyme Creatinine Liquid Reagents Assay	Roche Creatinine plus test	Equivalency
Quantitative	Quantitative	Same

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Specimen Type

Specimen Type
Diazyme Creatinine Liquid Reagents Assay	Roche Creatinine plus test	Equivalency
Human serum or urine.	Human serum or urine.	Same

Product Type

Diazyme Creatinine Liquid Reagents Assay	Roche Creatinine plus test	Equivalency
Calibrator, Controls, Reagent, Instrument	Calibrator, Controls, Reagent, Instrument	Same

Performance Comparison

Diazyme Creatinine Liquid Reagents Assay	Roche Creatinine plus test	Equivalency
Recovery: Average of 102.6%	Recovery: Average of 105.0%	Similar
Reportable Range:Serum: 0.14-13.56mg/dL(12-1200 µmol/L)Urine: 0.14-141.25 mg/dL(12-12500 µmol/L)	Reportable Range:Serum/Plasma: 2.7-2652 µmol/LUrine: 27-35360 µmol/L
Precision/Serum:Within Run: 0.1%-21.1%Total: 1.4%-3.0%	Precision/Serum:Within Run: 0.7%-0.9%Between Run: 1.6%-2.5%
Precision/Urine:Within Run: 0.31%-0.46%Total: 0.61%-2.64%	Precision/Urine:Within Run: 0.8%-1.0%Between Run: 2.1%-3.7%
Accuracy/Serum:Correlation Coefficient: 0.9981Slope/Intercept:$y = 0.9467x + 0.0643$	Accuracy/Serum:Correlation Coefficient: 0.999Slope/Intercept:$y = 0.989x + 0.036$
Accuracy/Urine:Correlation Coefficient: 0.9969Slope/Intercept:$y = 1.005x - 0.2979$	Accuracy/Urine:Correlation Coefficient: 0.999Slope/Intercept:$y = 0.999x + 0.037$

Control Comparison

Diazyme Creatinine Control	Dimension Vista Protein Control L, M, H	Equivalency
Liquid form	Liquid form	Same
Analyte specific Creatinine constituent	Analyte specific, C3, C4, Homocysteine,IGA, IGG, IGM and prealbuminconstituents	Same
Traceable to purified Creatinine -NISTSRM 914a standard	Traceable to purified S-adenosylhomocysteine standard	Same

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Rationale for Considering the Device Substantially Equivalent to Devices Approved for Inter-state Commerce

Roche Creatinine plus test method (K003261) was selected for comparing serum and urine samples with to the results generated by Diazyme Creatinine Liquid Reagents Assay. Detailed performance characteristics and comparison analysis are given in this filing and demonstrate substantial equivalence to predicate device that is currently being legally marketed.

The Diazyme Creatinine Liquid Reagents Assay is similar to the approved predicate test. The minor differences in the performances of the tests should not affect the safety and effectiveness of the Diazyme Creatinine Liquid Reagents Assay and offers users a rapid device to measure creatinine in human serum.

In summary, the dissimilar features between the Diazyme Creatinine Liquid Reagents Assay and devices currently legally marketed do not affect the safety or effectiveness of the device. This is supported by the accuracy data comparing serum and urine sample values obtained using the Diazyme Creatinine Liquid Reagents Assay with those obtained using the predicate device, Roche Creatinine plus test (K003261). Comparison analysis presented in this 510k submission together with the stability data also demonstrates that the Diazyme Creatinine control is substantially similar to the legally marketed device Dimension Vista Control (K063206).

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Description of the Device

Image /page/4/Figure/3 description: This image shows a series of chemical reactions. In the first reaction, Creatinine and H2O react with Creatininase to produce Creatine. In the second reaction, Creatine and H2O react with Creatinase to produce Sarcosine and Urea. In the third reaction, Sarcosine, H2O, and O2 react with SOD to produce Formaldehyde, Glycine, and H2O2. In the fourth reaction, 2H2O2, 4-AA, and TOOS react with POD to produce 4H2O and Quinone dye (λ max 556).

Intended Use of the Device:

Performance Characteristics

Diazyme Creatinine Liquid Reagents Assay is a two-reagent (R1 / R2) based kinetic assay system. The results are obtained in 10 minutes by measuring absorbance at 550nm. On line pretreatment removes endogenous creatine. The assay has a wide measuring range of 0.14-13.56 mg/dL (12-1200 umol/L) for Serum samples and 0.14 -- 141 mg/dL (12 to12500 umol/L) for Urine samples. The assay offers excellent precision as shown in the tables below:

Serum Testing	0.75 mg/dL(66.3 μM)	1.41 mg/dL(125 μM)	3.91 mg/dL(346 μM)	10.28 mg/dL(908.7 μM)
Within-Run Precision	$C_V% = 2.1%$	$C_V% = 1.1%$	$C_V% = 0.7%$	$C_V% = 0.1%$
Total Precision	$C_V% = 3.0%$	$C_V% = 1.9%$	$C_V% = 1.4%$	$C_V% = 1.4%$
Urine Testing	30 mg/dL(2652 μM)	87.13 mg/dL(7711 μM)	196.70 mg/dL(17407 μM)
Within-Run Precision	$C_V% = 0.36%$	$C_V% = 0.31%$	$C_V% = 0.46%$
Total Precision	$C_V% = 2.64%$	$C_V% = 0.76%$	$C_V% = 0.61%$

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Pre-market Notification Diazyme Creatinine Assay In method comparison studies, samples tested with Diazyme Creatinine Liquid Reagents Assay showed good correlation with Roche Creatinine plus (K003261) with correlation coefficients of 0.99 for both serum samples and urine samples. The average analytical recoveries were 97.8% to 109.4% for 11 creatinine serum samples and 97.0% to 104.3% for 22 creatinine urine samples.

Serum Urine Substance Concentration Substance Concentration Triglycerides 1000 mg/dL Triglycerides 1000 mg/dL Ascorbic acid 10 mmol/L Ascorbic acid 10 mmol/L Bilirubin 40 mg/dL Bilirubin 40 mg/dL Bilirubin Conjugated Bilirubin Conjugated 30 mg/dL 40 mg/dL Hemoglobin 500 mg/dL Hemoglobin 1000 mg/dL

We have conducted interference studies by spiking the substances to be tested to pooled human serum and urine, and found little interference at the indicated concentrations.

Conclusion: Comparison analysis presented in this 510k submission filing in the comparison section, together with linearity, precision and interference and other detailed studies, demonstrates that the Diazyme Creatinine Liquid Reagents Assay has excellent accuracy and is safe and effective. There is no significant deviation between the results obtained by Diazyme Creatinine Liquid Reagents Assay and the legally marketed predicate device (K003261) when testing clinical patient samples and is therefore substantially similar. Comparison analysis presented in this 510k submission together with the stability data demonstrates that the Diazyme Creatinine control is substantially similar to legally marketed device (K063206).

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/6/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with three overlapping wings, symbolizing health, services, and people. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the eagle.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

APR 2 3 2007

Diazyme Laboratories c/o Dr. Abhijit Datta Associate Director 3550 General Atomic Court San Diego, CA 92121

Re: K062105

Trade/Device Name: Diazyme Creatinine Liquid Reagents Assay Diazyme Creatinine Control Regulation Number: 21 CFR 862.1225 Regulation Name: Creatinine Test System Regulatory Class: Class II Product Code: JFY, JJX Dated: March 19, 2007 Received: March 21, 2007

Dear Dr. Datta:

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 vour 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 (240) 276-0490. 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 (240) 276-3150 or at its Internet address at http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Jean M. Cooper, M.S., D.V.M.

Jean M. Cooper, M.S., D.V.M. 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:

K062105

Device Name:

Indications for Use:

Diazyme Creatinine Liquid Reagents Assay Diazyme Creatinine Control

Prescription Use X AND/OR

Over-The-Counter Use (21 CFR 801 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)
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Carol C Benson
Division Sigh Off

Division Sigh-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

K062105

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.