For in vitro diagnostic use with Exigent Diagnostics CareSide Analyzer to measure creatinine in whole blood, plasma or serum specimens by professionals to aid in the diagnosis and treatment of renal diseases.

Device Description

CareSide™ Creatinine cartridges are used with the Exigent Diagnostics CareSide™ Analyzer to measure creatinine concentration in anti-coagulated whole blood, plasma or serum specimens. The CareSide™ Creatinine cartridge, a single use disposable in vitro diagnostic test cartridge, aids in specimen separation and delivers a measured volume of plasma or serum to a dry film to initiate the measurement of creatinine concentration. The film cartridge (patent pending) contains all reagents necessary to measure creatinine concentration. When used in conjunction with the CareSideTM BUN cartridge on the CareSide™ Analyzer, the analyzer calculates a BUN to creatinine ratio.

AI/ML Overview

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CareSide™ Creatinine Device Performance Study Analysis

1. Table of Acceptance Criteria and Reported Device Performance

The provided document primarily focuses on demonstrating substantial equivalence to a predicate device rather than explicitly defining "acceptance criteria" against which to measure the device's performance in a standalone context. However, it does present comparative performance characteristics between the CareSide™ Creatinine and the predicate device (Vitros Creatinine DT Slides). We can infer "performance standards" or expected performance based on these comparisons and the predicate device's characteristics.

Performance Metric	CareSide™ Creatinine Reported Performance	Predicate Device Performance / Implied Acceptance Criteria
Detection Limit	0.2 mg/dL	Not provided for predicate (but assumed to be comparable or better)
Reportable Range	0.2 to 16 mg/dL	0.01 to 15 mg/dL (CareSide™ exceeds on high end, slightly less on low end)
Accuracy (Mean Recovery)	99%	Not provided for predicate (but an implied expectation of high accuracy)
Precision (Total CV)	4.2% at 9 mg/dL	3.3% at 10 mg/dL (Predicate device shows slightly better precision)
Method Comparison (vs. Predicate)	CareSide™ = 1.08 (Vitros Creatinine DT) - 0.38, r=0.99	Strongly correlated (r=0.99) with predicate, indicating substantial agreement.
Linearity	Mean deviation approx 4%, r>0.99	Not provided for predicate (but implied expectation of good linearity across the reportable range)
Interference	No significant interference observed at tested concentration of interferents (Ammonium PO₄, Ascorbic Acid, Bilirubin, 5-fluorocytosine, Glucose, Hemoglobin, Triglycerides, Urea Nitrogen)	Not provided for predicate (but implied expectation of minimal interference for common substances)
Specimen Types & Anticoagulants	No clinically significant difference between heparinized whole blood, serum, heparin plasma, and EDTA plasma.	No clinically significant difference between serum and heparin plasma. Whole blood is unsuitable for predicate.
Expected Values	0.4 to 0.9 mg/dL (female); 0.6 to 1.3 mg/dL (male) (Central 95% interval)	0.5 to 1.2 mg/dL (female); 0.7 to 1.4 mg/dL (male) (Central 95% interval)

Study Proving Acceptance Criteria:

The document describes several "Comparative Performance Characteristics" that serve as the basis for proving the device meets the implied acceptance criteria for substantial equivalence to the predicate device. These include:

Detection Limit: Directly reported.
Reportable Range: Compared against the predicate.
Accuracy: Mean recovery study reported.
Precision: Total CV reported.
Method Comparison: A regression analysis (CareSide™ vs. Vitros Creatinine DT) showing strong correlation (r=0.99). This is a primary study for demonstrating equivalence.
Linearity: Reported with mean deviation and correlation coefficient.
Interference: A study testing various common interferents at specified concentrations.
Specimen Types & Anticoagulants: A study assessing performance across different sample types.
Expected Values: Clinical range established.

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

The provided text does not explicitly state the sample sizes used for the various tests (e.g., accuracy, precision, method comparison, linearity, interference, specimen type studies). Similarly, the data provenance (country of origin, retrospective/prospective) is not mentioned. These details would typically be found in more comprehensive study reports or validation binders.

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

The document does not mention the use of experts to establish ground truth in the context of radiologists or similar clinical reviewers. This device is an in vitro diagnostic (IVD) for measuring a biochemical marker. Ground truth for such devices is typically established through a reference method, which is stated as HPLC (High-Performance Liquid Chromatography) for both the CareSide™ and the predicate device. Therefore, the "ground truth" is analytical, not based on expert consensus of interpretive results.

4. Adjudication Method for the Test Set

As the ground truth is established analytically (via HPLC) rather than by expert interpretation, an "adjudication method" in the sense of reconciling differing expert opinions (e.g., 2+1, 3+1) is not applicable or described.

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

No MRMC comparative effectiveness study was done or is applicable. This device is an automated in vitro diagnostic system for measuring creatinine levels from blood samples. It is not an AI-assisted diagnostic imaging tool that would involve human readers or interpretation of complex medical images.

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

Yes, this is essentially a standalone (algorithm only) device. The CareSide™ Creatinine cartridge and CareSide™ Analyzer automatically measure creatinine concentration. While a laboratory professional introduces the sample and operates the device, the measurement itself is automated and does not involve human interpretation of the analytical result (e.g., a "human-in-the-loop" for image review). The performance metrics reported (accuracy, precision, linearity, etc.) describe the standalone analytical performance of the device system.

7. The Type of Ground Truth Used

The ground truth used for performance comparison and validation is analytical measurement by High-Performance Liquid Chromatography (HPLC). HPLC is explicitly listed as the "Reference Method" (Page 13b). This is a gold standard laboratory technique for quantifying substances like creatinine.

8. The Sample Size for the Training Set

The document does not provide information on a "training set" sample size. This is common for IVD devices of this nature from this era (1998). While the device's internal algorithms (e.g., for calculating creatinine concentration from reflectance measurements) would have been developed and optimized, the concept of a distinct, labeled "training set" in the context of modern machine learning validation protocols is not explicitly addressed here. The reported "Calibration" mentions "Calibration information bar-coded on each cartridge" and that "Calibration information may change with each lot," implying a continuous process rather than a fixed training set used for a singular AI model.

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

As there is no explicit mention of an identifiable "training set" in the modern AI sense, the method for establishing its ground truth is not described. For the underlying analytical methodology, calibration materials with known creatinine concentrations (traceable to a reference method like HPLC) would be used to establish the relationship between the reflectance signal and creatinine concentration.

Summary

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Mar. 1999 10:040M P7

Exigent Diagnostics, Inc.

Page 13

CareSide™ Creatinine Premarket Notification

MAR 3 0 1998 revised on March 23, 1998

CareSide™ Creatinine Safety and 510(k) Summary: V. Effectiveness

I. Applicant Information

A. Applicant Name
Applicant/Manufacturer Address B,
C. Telephone Number
D. Contact Person
E. FAX Number
F. e-Mail Address
G. Date 510(k) Summary prepared

Device Information 11.

Device Name (Trade) A.
Device Name (Classification) B.
Device Classification C.

CareSide™ Creatinine

asarchk@worldnet.att.net

Exigent Diagnostics, Inc.

Kenneth B. Asarch, Pharm.D., Ph.D.

6100 Bristol Parkway Culver City, CA 90230

310-338-6767

310-338-6789

February 11, 1998

Creatinine test system Clinical chemistry panel Creatinine test system Regulation Number: 21 CFR 862.1225 Regulatory Class II Classification Number: 75JFY Tier 1 None applicable

D. Device Tier
Special controls and E. performance standards

III. Substantial Equivalence Claim

A. General equivalency claim
The ability to monitor analyte-specific biochemical reactions in dry film and other formats is widely recognized and has gained widespread acceptance for use in chemistry assays.

Creatinine in vitro diagnostic products, in both dry film and other formats, are already on the U.S. market, including creatinine products which utilize creatinine deaminasc catalyzed generation of ammonia by reaction non-enzymatically with bromophenol blue indicator dye.

B. Specific equivalency claim

This CareSide™ Creatinine test is substantially equivalent in principle, intended use, and clinical performance to the currently marketed Vitros slides for the quantitative measurement of Creatinine on the Vitros DT 60 II.

Name of Predicate Device:	Johnson and Johnson's (formerly Eastman Kodak,Inc.) Vitros CREA Slides (blank corrected method)for Johnson and Johnson's Vitros DT 60 (formerlyEastman Kodak's DT 60 II).
Predicate Device 510K number:	K912844/A
Product Code:	75JLA

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Exigent Diagnostics, Inc. Page 13a

CareSide™ Creatinine Premarket Notification revised on March 23, 1998

Device Description IV.

Explanation of Device Function A.

Each Exigent Diagnostics CareSide™ Creatinine cartridge consists of a creatininespecific multi-layer reagent film mounted in a plastic base with a hinged lid. The user introduces the anti-coagulated whole blood, serum, or plasma specimen into the cartridge deposition well, closes the lid and inserts the cartridge into the sample Exigent Diagnostics CareSide™ Analyzer.

Once loaded, the CareSide™ analyzer scans the cartridge barcode, brings the cartridge and the contained specimen to 37°C, and spins the cartridge to move the sample from the sample deposition well into the cartridge channels and chambers. As the cartridge continues to spin, the blood cells are separated from the plasmalserum and the cells accumulate in the separation well. Ten microliters of plasma (or serum, as applicable) remain in the metering passage. Any excess sample flows into an overflow well.

The ten microliters of plasma (or serum, as applicable) is automatically dispensed onto the multi-layer reagent film. The spreading layer distributes the sample evenly on the film and filters large molecular weight components such as protein and dye fragments before the specimen enters the ammonia removal layer. Endogenous ammonia is removed by the enzymatic conversion to L-glutamic acid through the action of glutamate dehydogenase (GLDH) in the presence of a-ketoglutaric acid and NADPH. A separation layer prevents mixing the former reaction with the next layer in which the enzymc creatinine deiminase (CD) acts on creatinine in the presence of water to form ammonia gas and N-methylhydantoin. The ammonia gas crosses the gas penneation layer to enter the detection layer where it reacts with bromophenol blue to form a blue dye.

Test Reaction Sequence:

NH3 + a-ketoglutaric acid + NADPH - 040 > L-glutamic acid + NADP* Creatinine + H2O -- > N-Inethylhydantoin + NI3

Bromophenol blue + NH3 -> Blue dye

As the cartridges spin, photodiodes measure reflectance of light emitted by waveleugthspecific light emitting diodes (LEDs) at a fixed time. The analyzer uses the reflectance measurements and the lot-specific standard curve to calculate creatinine concentration.

Test Summary B.

Creatinine is produced during muscle contraction when the high-energy compound phosphocreatine degrades into creatine, which subsequently dehydrates into circulating creatinine. Creatinine levels in blood serve as an indicator of total muscle mass and activity, and of renal function. Decreased levels of creatinine are seen in cases of muscular dystrophy. Increased creatinine levels arc found in cases of kidney disease and urinary tract obstruction. Creatinine concentration in blood is closely correlated with the kidney's glomerular filtration rate (GFR), and the creatinine clearance rate is used as an estimate of the GFR. The creatinine clearance rate, estimated from the blood creatinine concentration, is used to determine or to adjust the dosage of certain drugs which are excreted via glomerular filtration in the kidneys.

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Exigent Diagnostics, Inc. Page 13b

CareSide™ Creatinine Premarket Notification revised on March 23, 1998

V. Intended Use

ん. Intended Use

The CareSide™ Creatinine cartridge is intended for in vitro diagnostic use in conjunction with the Exigent Diagnostics CareSide™ Analyzer to quantitatively measure creatinine cooncentration in anti-coagulated whole blood, plasma or serum by laboratory professionals. When used in conjunction with the Exigent Diagnostics CareSide™ BUN test cartridge on the Exigent Diagnostics CareSide™ Analyzer, the creatinine product may be used to calculate a BUN to creatinine ratio. The CareSide™ Creatinine test aids in the diagnosis and treatment of renal diseases.

Indications for Use B.

This product is indicated for use with patients with various renal diseases.

Technological Characteristics VI.

A. Similarities

	CareSide™ Creatinine	Vitros Creatinine DT Slides
Intended Use	Primarily to aid in the diagnosisand treatment of renal diseases.	Same
Indications	For in vitro diagnostic use.For professional use only.	Same
Measurement	Quantitative	Same
Method Principle	Dry film based creatininedeiminase conversion ofcreatinine to ammonia andreaction with ammoniaindicating dye. Chromogenquantitated by reflectancemeasurement after fixed time.	Same except that endogenouscreatinine is measured andsubtracted rather thanenzymatically eliminated.
Specimen dilution	Not required	Same
Materials Source	Creatinine deiminase(Bacillus sp)Indicator - Bromocresol blus(synthetic)	Creatinine deiminase(source unknown)Indicator - Bromocresol blus(synthetic)
Detector	Reflectance (570 nm)	Reflectance (605 nm)
Test time	Approximately 4 minute warm-up (on-board) plus 5 minute testtime.	15 minutes slide warm-up (off-line) plus 5 minutes test time.
Reference Method	HPLC	HPLC
Sample Type	Serum, plasma, anti-coagulatedwhole blood (wb) [wb appliedsample, plasma test sample]	serum, plasma
Specimen volume	10 µl test volume(85 ± 15 µl applied volume)	10 µl
Calibration	Calibration information bar-coded on each cartridge.Calibration information maychange with each lot.	Run Vitros DT II calibratorswhenever a new slide lot isused or when necessary.
Quality Control	2 levels	Same
Reporting Units	mg/dL or µmol/L	Same
Reaction Temp.	37 °C	Same

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Exigent Diagnostics, Inc. Page 13c

CareSide™ Creatinine Premarket Notification revised on March 23, 1998

B. Differences

	CareSide™ Creatinine	Vitros Creatinine DT Slides
Direct bloodspecimen	Yes, anti-coagulated wholeblood	No, requires separation ofwhole blood prior to sampleapplication
Reportable range	0.2 to 16 mg/dL	0.01 to 15 mg/dL
Accuratepipetting	Not required	Required
Reagent pre-warming	Not required	Required

Comparative Performance Characteristics C.

	CareSide™ Creatinine	Vitros Creatinine DT Slides
Detection limit	0.2 mg/dL	Not provided
Reportable range	0.2 to 16 mg/dL	0.01 to 15 mg/dL
Accuracy	Mean recovery 99%	Not provided
Precision	Total CV, 9 mg/dL, 4.2%	Total CV, 10 mg/dL, 3.3%
Method comparison	CareSide™ = $1.08 (Vitros Creatinine DT) - 0.38, r=0.99$
Linearity	Mean deviation approx 4%,r>0.99	Not provided
Interference	No significant interference observed at tested concentration of interferent:Ammonium PO₄, 500 μMAscorbic Acid, 10 mg/dLBilirubin, 20 mg/dL5-fluorocytosine, 80 μg/mLGlucose, 600 mg/dLHemoglobin, 500 mg/dLTriglycerides 3000 mg/dLUrea Nitrogen (BUN), 100 mg/dL	Not provided
Specimen Types & Anticoagulants	No clinically significant difference between heparinized whole blood, serum, heparin plasma, and EDTA plasma.	No clinically significant difference between serum and heparin plasma. Whole blood is unsuitable.
Expected Values	0.4 to 0.9 mg/dL (female)0.6 to 1.3 mg/dL (male)Central 95% interval	0.5 to 1.2 mg/dL (female)0.7 to 1.4 mg/dL (male)Central 95% interval

D. Conclusion

The nonclinical and clinical data provided demonstrate that the CareSide™ Creatinine product is as safe, effective, and performs as well as or better than the legally marketed predicate device.

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Image /page/4/Picture/1 description: The image contains the text "Public Health Service". The text is black and is centered horizontally. The background is white.

Image /page/4/Picture/2 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo features a stylized eagle or bird-like symbol with three curved lines forming its body and wings. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the bird symbol. The text is in all caps and is in a sans-serif font.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

MAR 3 0 1998

Kenneth B. Asarch, Ph.D. Vice President Quality Systems and Regulatory Affairs Exigent Diagnostics Inc. 6100 Bristol Parkway Culver City, California 90230

K980043 Re : CareSide™ Creatinine Regulatory Class: II Product Code: JFY Dated: December 30, 1997 Received: January 6, 1998

Dear Dr. Asarch:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to 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). 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 (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements Please note: concerning your device in the Federal Register. this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations .

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Paqe 2

This letter will allow you to begin marketing your device as described in your 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 advice for your device on our labeling requlation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "dsmo@fdadr.cdrh.fda.qov".

Sincerely yours,

Steven Autman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Exigent Diagnostics, Inc. Page 15

CareSide™ Creatinine Promarket Notification Revised on March 23, 1998

VII. Indications for Use

510(k) Number: To be assigned
CareSide™ Creatinine Device Name:

For in vitro diagnostic use with Exigent Diagnostics CareSide Analyzer to Indications for use: measure creatinine in whole blood, plasma or serum specimens by professionals to aid in the diagnosis and treatment of renal diseases.

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K980043

/Prescription use

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.