For in vitro diagnostic use with the CARESIDE™ Analyzer to quantitatively measure inorganic phosphorus from anti-coagulated whole blood, plasma or serum specimens to aid in the diagnosis and treatment of various disorders, including parathyroid gland and kidney diseases, and vitamin D imbalance. It is intended for professional laboratory use: not for point of care or physician office laboratory use.

Device Description

CARESIDE™ Phosphorus cartridges are used with the CARESIDE™ Analyzer to quantitatively measure phosphorus concentration in anti-coagulated whole blood, plasma or serum specimens. The CARESIDE™ Phosphorus 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 phosphorus concentration. The film cartridge (patent pending) contains all reagents necessary to measure phosphorus concentration.

AI/ML Overview

Here's an analysis of the acceptance criteria and study information for the CARESIDE™ Phosphorus device based on the provided text:

CARESIDE™ Phosphorus Device Performance Analysis

1. Acceptance Criteria and Reported Device Performance

The submission focuses on establishing substantial equivalence to a predicate device rather than defining new, explicit numerical acceptance criteria for overall performance. Instead, the acceptance is demonstrated by showing comparable or better performance across various analytical characteristics.

Acceptance Criteria Category	CARESIDE™ Phosphorus Reported Performance	Predicate Device (Vitros PHOS DT Slides) Reported Performance
Detection Limit	0.5 mg/dL	0.5 mg/dL
Reportable Range	0.5 to 15 mg/dL	0.5 to 13 mg/dL
Accuracy	Mean recovery 97%	Not provided
Precision	Total CV, 3.5 mg/dL, 4.0%	Total CV, 4.9 mg/dL, 3.7%
Method Comparison	CARESIDE™ = 0.99 (Vitros PHOS DT) + 0.49, r = 1.00 (against Vitros PHOS DT)	(Implicitly, this is the reference)
Linearity	Linearity by mixing and by dilution yielded slope and correlation coefficients within acceptable limits.	Not provided
Interference	No significant interference observed at tested concentrations of: Ascorbic Acid (10 mg/dL), Bilirubin (20 mg/dL), Hemoglobin (100 mg/dL), d-Mannitol (800 mg/dL), Triglycerides (1500 mg/dL)	Not provided
Specimen Types	No clinically significant difference between sodium heparinized whole blood, serum, sodium heparin plasma, and EDTA plasma.	No clinically significant difference between serum, heparin plasma, or EDTA plasma. Whole blood is unsuitable.
Expected Values	2.2 to 4.4 mg/dL (Central 95%)	2.5 to 4.5 mg/dL (Central 95%)

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

The document does not explicitly state the sample sizes used for the various performance characteristic tests (e.g., accuracy, precision, method comparison, linearity, interference). It only lists the results.

The data provenance (country of origin, retrospective/prospective) is not specified. However, the context of a 510(k) submission to the US FDA implies that the studies were conducted to support US market approval.

3. Number of Experts Used to Establish Ground Truth and Qualifications

This device is an in vitro diagnostic (IVD) for quantitative measurement of a biochemical analyte (phosphorus). The "ground truth" for such devices is typically established through:

Reference methods (e.g., Phosphomolybdate Reduced method mentioned in the document).
Certified reference materials or calibrators.
Comparison to a legally marketed predicate device, which itself would have been validated against established analytical principles and reference methods.

The document does not mention the use of human experts or their qualifications for establishing ground truth for individual test cases, as this is not typically relevant for the analytical validation of a chemical assay. The "experts" in this context are implicitly the developers and clinical chemists who ensured the assay's analytical accuracy.

4. Adjudication Method for the Test Set

Adjudication methods (e.g., 2+1, 3+1) are typically used in studies involving subjective interpretation, such as imaging diagnostics where expert readers review cases and reach a consensus. For a quantitative chemical analyzer like the CARESIDE™ Phosphorus, this type of adjudication is not applicable. The device provides a numerical result, which is then compared against established analytical standards or reference methods.

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

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not conducted or mentioned. This type of study is relevant for diagnostic tools that involve human interpretation (e.g., radiology AI), assessing how AI assistance impacts human reader performance. The CARESIDE™ Phosphorus device is an automated chemical analyzer, not an AI-assisted diagnostic interpretation tool.

6. Standalone (Algorithm Only) Performance Study

Yes, a standalone performance study was conducted. All the reported performance characteristics (detection limit, reportable range, accuracy, precision, method comparison, linearity, interference, specimen types) represent the performance of the CARESIDE™ Phosphorus device and its integrated analyzer without human-in-the-loop interpretation. The device itself performs the measurement and calculation, making its reported performance inherently "standalone." The comparison to the predicate device essentially assesses its standalone performance against another standalone device.

7. Type of Ground Truth Used

The ground truth for this device's performance was established through:

Reference Method Comparison: The "Reference Method" listed for both the CARESIDE™ Phosphorus and the predicate is "Phosphomolybdate Reduced," indicating that this established analytical method would have been used as a benchmark for comparison.
Analytical Standards/Calibrators: The document mentions "lot-specific standard curve to calculate phosphorus concentration" and "Run Vitros DT II calibrators," implying the use of traceable standards and calibrators for accurate quantitative measurement.
Predicate Device Comparison: A significant part of the safety and effectiveness claim is based on its performance in comparison to the legally marketed Vitros PHOS DT Slides. The predicate device's results would serve as a 'clinical ground truth' for the comparative effectiveness.

8. Sample Size for the Training Set

The document does not specify a separate "training set" or its sample size. For an IVD device like this, the development process typically involves:

Method Development & Optimization: Using various samples (unknown quantity) to refine reagents, reaction conditions, and instrument parameters.
Calibration: Using a set of samples with known concentrations to establish the relationship between the measured signal and the analyte concentration. The device uses "lot-specific standard curve" and mentions "Calibration information bar-coded on each cartridge." This implies a calibration process, which could be considered analogous to training in an AI context, but isn't typically referred to as a "training set" with specific sample numbers in IVD submissions unless it's a machine learning algorithm.

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

As noted above, a distinct "training set" as understood in machine learning is not explicitly detailed. However, the "ground truth" for the calibration and development of the device would have been established through:

Reference Methods: Using the Phosphomolybdate Reduced method or other highly accurate, established laboratory techniques to determine the true phosphorus concentration in samples used for calibration curve generation and method development.
Certified Reference Materials: Utilizing commercially available reference materials with precisely known phosphorus concentrations.

Summary

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JUN 25 1998

CARESIDE™ PHOSPHORUS 510(K) SUMMARY: SAFETY AND EFFECTIVENESS

I. Applicant Information

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

II. Device Information

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

CARESIDE, Inc.

6100 Bristol Parkway Culver City, CA 90230 310-338-6767 Kenneth B. Asarch, Pharm.D., Ph.D. 310-338-6789 asarchk @ worldnet.att.net June 11, 1998

CARESIDE™ Phosphorus

Phosphate test system Clinical chemistry panel Phosphate test system Regulation Number: 21 CFR 862.1580 Regulatory Class I Classification Number: 75CEO None applicable

D. Special controls and 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.

Phosphorus in vitro diagnostic products, in both dry film and other formats, are already on the U.S. market. These products utilize dry film and other formats. These products utilize either direct complexation of inorganic phosphate or coupled reactions to form a chromogen. For example,

complexation of inorganic phosphate with ammonium l. Dry film molybdate coupled to conversion to heteropolymolbydate blue dye by reaction with p-methylaminophenol sulfate.
Vitros PHOS DT 60 slides for Vitros DT 60 II example: (formerly Kodak DT 60 II), Johnson & Johnson Clinical Diagnostics, Inc.
1. Wet chemistry complexation of inorganic phosphate with ammonium molybdate. Ammonium molybdate complex is reduced and the resulting change in absorbance at 340/660 nanometers is proportional to the amount of inorganic phosphorous present in the sample.
- Phosphate XTS™ for Olympus AU5200, example: Olympus America, Inc.

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Specific equivalency claim B.

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

Name of Predicate Device:	Johnson and Johnson's (formerly Eastman Kodak,Inc.) Vitros PHOS Slides for Johnson and Johnson'sVitros DT 60 (formerly Eastman Kodak's DT 60 II).
Predicate Device 510K number:	K912844/A
Product Code:	75CEO

IV. Device Description

Explanation of Device Function A.

Each CARESIDE™ Phosphorus cartridge consists of a phosphorus-specific multi-layer reagent film mounted in a plastic base with a hinged lid. The user introduces the anticoagulated whole blood, serum, or plasma specimen into the cartridge sample deposition well, closes the lid and inserts the cartridge into the CARESIDE™ Analyzer.

Once loaded, the CARESIDE™ analyzer scans the cartridge barcode, brings the cartridge and the contained specimen to 37℃, 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 plasma/serum and the cells accumulate in the separation well. Approximately ten microliters of plasma (or serum, as applicable) remain in the metering passage. Any excess sample flows into an overflow well.

The plasma (or serum, as applicable) is automatically dispensed onto the multi-layer reagent film. The test specimen is distributed uniformly by the spreading layer. Large molecular components, such as proteins and dye components are filtered out as the specimen passes into the reaction layer. Purine nucleoside phosphorylase (PNP) catalyzes the reaction of the inorganic phosphorus (H2PO4, HPO4") reacts with xanthosine to form xanthine and ribose-1-phosphoric acid. Xanthine oxidase (XOD) then catalyzes the oxidation of xanthine in the presence of water and oxygen to produce uric acid and hydrogen peroxide. Peroxidase (POD) then catalyzes the conversion of leuco dye and hydrogen peroxide to produce an imidazole blue dye and water. The intensity of the color as measured by the amount of reflected light at 655 nanometers directly relates to the specimen inorganic phosphorus concentration.

Test Reaction Sequence:

Xanthosine + inorganic phosphate -> Xanthine + Ribose-1-phosphoric acid

Xanthine + H2O + Oxygen -> Uric Acid + Hydrogen Peroxide

Hydrogen Peroxide + Leuco-dye -> Imidazole Blue Dye + 2 H20

As the cartridge spins, a photodiode measures film reflectance of light emitted from a wavelength-specific light emitting diode (LED) at a fixed time. The analyzer uses the reflectance measurements and the lot-specific standard curve to calculate phosphorus concentration.

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B. Test Summary

Phosphate is required for generation of bony tissue and functions in the metabolism of glucose and lipids, in the maintenance of acid-base balance, and in the storage and transfer on energy from one site in the body to another. Phosphate enters the cell with glucose and is lowered after carbohydrate ingestion. For these reasons, blood phosphate levels must be controlled within narrow limits.

Determination of whole blood, serum or plasma phosphorus levels is used in the diagnosis and treatment of various disorders including parathyroid gland and kidney diseases, and vitamin D imbalance. Phosphorus levels are always evaluated in relation to calcium levels because there is an inverse relationship between the two. When phosphate rises rapidly and calcium drops, there is a high risk of arrhythmias and muscle twitching. Excess serum levels of one causes the kidneys to excrete the other.

Hypophosphatemia may be seen in hyperparathyroidism, Fanconi's syndrome, vitamin D deficiency in children (rickets) and adults (osteomalacia), chronic use of antacids, chronic alcoholism, malabsorption syndromes, hyperinsulinism and occasionally during hyperalimentation therapy.

Causes of hyperphosphatemia include chronic renal failure, Addison's disease, excessive ingestion of vitamin D. cytotoxic treatment of certain leukemias and lymphomas, metastatic bone tumors, hypocalcemia, diabetic ketoacidosis, and healing bone fractures.

V. Intended Use

A. Intended Use
The CARESIDE™ Phosphorus cartridge is intended for in vitro diagnostic use in conjunction with the CARESIDE™ Analyzer to quantitatively measure phosphorus concentration in anti-coagulated whole blood, plasma or serum. The CARESIDE™ Phosphorus test aids in the diagnosis and treatment of various disorders including parathyroid gland and kidney diseases, and vitamin D imbalance.

B. Indications for Use

For in vitro diagnostic use with the CARESIDE™ Analyzer to quantitatively measure inorganic phosphorus from anti-coagulated whole blood, plasma or serum specimens to aid in the diagnosis and treatment of various disorders. including parathyroid gland and kidney diseases, and vitamin D imbalance. It is intended for professional laboratory use: not for point of care or physician office laboratory use.

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VI. Technological Characteristics

Similarities A.

	CARESIDETM Phosphorus	Vitros PHOS DT Slides
Intended Use	Primarily to aid in the diagnosisand treatment of phosphateregulation disorders such asparathyroid gland disease,kidney disease, or vitamin Dimbalance.	Same
Indications	For in vitro diagnostic use.For laboratory professional use:not for point of care orphysician office laboratory use.	For in vitro diagnostic use
Measurement	Quantitative	Same
Method Principle	Dry film based enzymaticgeneration of hydrogenperoxide from inorganicphosphate. Reaction ofchromogen with hydrogenperoxide to form blue. Dyequantitated by reflectancemeasurement after fixed time.	Dry film, complexation ofinorganic phosphate withammonium molybdate coupledto conversion toheteropolymolbydate blue dyeby reaction with p-methylaminophenol sulfate
Specimen dilution	Not required	Same
Materials	Xanthosine purine nucleosidephosphorylase,Diarylimidazole leuco-dye	p-methylaminophenol sulfate,ammonium molybdate
Detector	Reflectance (655 nm)	Reflectance (660 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	Phosphomolybdate Reduced	Phosphomolybdate Reduced
Sample Type	Serum, plasma, anti-coagulated(wb) [wb applied sample,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 mmol/L	Same
Reaction Temp.	37 °C	Same

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…

B. Differences

	CARESIDE™ Phosphorus	Vitros PHOS DT Slides
Direct bloodspecimen	Yes, whole blood	No, requires separation ofwhole blood prior to sampleapplication
Reportable range	0.5 to 15 mg/dL	0.5 to 13 mg/dL
Accuratepipetting	Not required	Required
Reagent pre-warming	Not required	Required

C. Comparative Performance Characteristics

	CARESIDE™ Phosphorus	Vitros PHOS DT Slides
Detection limit	0.5 mg/dL	0.5 mg/dL
Reportable range	0.5 to 15 mg/dL	0.5 to 13 mg/dL
Accuracy	Mean recovery 97%	Not provided
Precision	Total CV, 3.5 mg/dL, 4.0%	Total CV, 4.9 mg/dL, 3.7%
Methodcomparison	CARESIDE™ = 0.99 (Vitros PHOS DT) + 0.49, r = 1.00
Linearity	Linearity by mixing and bydilution yielded slope andcorrelation coefficients withinacceptable limits.	Not provided
Interference	No significant interferenceobserved at testedconcentration of interferent:Ascorbic Acid, 10 mg/dLBilirubin, 20 mg/dLHemoglobin, 100 mg/dLd-Mannitol 800 mg/dLTriglycerides 1500 mg/dL	Not provided
Specimen Types& Anticoagulants	No clinically significantdifference between sodiumheparinized whole blood,serum, sodium heparinplasma, and EDTA plasma.	No clinically significantdifference between serum,heparin plasma, or EDTAplasma. Whole blood isunsuitable.
Expected Values	2.2 to 4.4 mg/dLCentral 95%	2.5 to 4.5 mg/dLCentral 95%

D. Conclusion

The nonclinical and clinical data provided demonstrate that the CARESIDETM Phosphorus product is as safe, effective, and performs as well as or better than the legally marketed Vitros DT 60.

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Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features the department's name arranged in a circular fashion around a symbol. The symbol is a stylized representation of three human figures, possibly symbolizing health and well-being. The logo is black and white.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JUN 25 1998

Kenneth B. Asarch, Ph.D. . VP Quality Systems and Regulatory Affairs CareSide, Inc. 6100 Bristol Parkway Culver City, California 90230

K981610 Re: CareSide™ Phosphorus Regulatory Class: I Product Code: CEO Dated: April 27, 1998 Received: April 30, 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 The general controls provisions of the Act of the Act. include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions aqainst 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 Requlations, Title 21, Parts 800 to 895. ਸਿ 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 In addition, FDA may publish further announcements action. concerning your device in the Federal Reqister. Please note: 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 requlations.

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Page 2

Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770) 488-7655.

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 regulation (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 premarket notification" (21 CFR 807.97). 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 "http://www.fda.gov/cdrh/dsmamain.html".

Sincerely yours,
Steven Sitman

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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CARESIDE, Inc. Page 5

INDICATIONS FOR USE

K981610 510(k) Number:

Device Name:

CARESIDE™ Phosphorus

For in vitro diagnostic use with the CARESIDE™ Analyzer to quantitatively Indications for use: measure inorganic phosphorus from anti-coagulated whole blood, plasma or serum specimens to aid in the diagnosis and treatment of various disorders, including parathyroid gland and kidney diseases, and vitamin D imbalance. It is intended for professional laboratory use: not for point of care or physician office laboratory use.

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K981610

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use
(Per 21 CFR 801.109)

Over-The-Counter Use (Optional Format 1-2-96)

Regulation Number and Section

§ 862.1580 Phosphorus (inorganic) test system.

(a)
Identification. A phosphorus (inorganic) test system is a device intended to measure inorganic phosphorus in serum, plasma, and urine. Measurements of phosphorus (inorganic) are used in the diagnosis and treatment of various disorders, including parathyroid gland and kidney diseases, and vitamin D imbalance.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.