For in vitro diagnostic use with the CARESIDE Analyzer™ to quantitatively measure total calcium from heparinized whole blood, heparin plasma or serum specimens to aid in diagnosis and treatment of patients with parathyroid disease, a variety of bone diseases, chronic renal disease, and tetany. It is intended for professional laboratory use: not for point of care or physician office laboratory use.

Device Description

CARESIDE™ Calcium cartridges are used with the CARESIDE Analyzer™ to measure calcium concentration in heparinized whole blood, heparin plasma or serum specimens. The CARESIDE™ Calcium cartridge, a single use disposable in vitro diagnostic test carridge, delivers a measured volume of serum or plasma to a dry film to initiate the measurement of calcium concentration. The film cartridge (patent pending) contains all reagents necessary to measure calcium concentration.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the CARESIDE™ Calcium device, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly define strict, numerical "acceptance criteria" for precision or accuracy that the device must meet in a pre-defined way. Instead, it presents performance characteristics and concludes that the device is "as safe, effective, and performs as well as or better than the legally marketed predicate device." The comparison is primarily done against the predicate device's characteristics and general expectations for such a device.

However, we can infer some "acceptance" in terms of reported performance:

Performance Metric	Acceptance Criteria (Implicitly based on comparison or general expectation)	Reported Device Performance (CARESIDE™ Calcium)
Detection Limit	Comparable to predicate (3 mg/dL) or acceptable for clinical use	4.2 mg/dL
Reportable Range	Comparable to predicate (3 to 14 mg/dL) or acceptable for clinical use	4.2 to 14 mg/dL
Accuracy (Mean Recovery)	Acceptable for clinical use (not explicitly stated for predicate)	98%
Precision (Total CV)	Comparable to predicate (1.6% at 11.9 mg/dL) or acceptable for clinical use	7.8% at 6.5 mg/dL
Method Comparison	Strong correlation (r) to a reference method, slope and intercept close to 1 and 0, respectively.	CARESIDE™ = 0.90 (Reference Method) + 1.09 mg/dL, r = 0.95
Linearity	Slope and correlation coefficient within acceptable limits	Linearity yielded slope and correlation coefficient within acceptable limits.
Interference	No significant interference from common substances	No significant interference observed at tested [Ascorbic Acid, 10 mg/dLBilirubin, 10 mg/dLHemoglobin, 250 mg/dLMagnesium 2.5 mmol/LTriglycerides 600 mg/dL]

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

The document does not explicitly state the sample size used for the test set for any of the performance metrics (accuracy, precision, method comparison, linearity, interference).

The data provenance is also not specified. It's unclear if the data is from a specific country, or if it is retrospective or prospective.

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

This information is not provided in the document. For an in vitro diagnostic device like this, ground truth is typically established by comparing the device's measurements to a recognized "gold standard" laboratory method, rather than expert consensus on interpretation.

4. Adjudication Method for the Test Set

This is not applicable and not provided for this type of in vitro diagnostic device study. Adjudication methods like "2+1" or "3+1" are typically used in studies involving human interpretation (e.g., radiology reads) where there can be disagreement among experts. For quantitative measurements, the comparison is made directly to a reference method.

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

A MRMC comparative effectiveness study was not done. This type of study is relevant to imaging or diagnostic devices where human readers interpret results, and the AI's impact on their performance is being assessed. The CARESIDE™ Calcium is a diagnostic test kit for quantitative measurement and does not involve human interpretation in the same way.

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

Yes, a standalone study was done. The performance metrics (detection limit, reportable range, accuracy, precision, method comparison, linearity, interference) provided for the CARESIDE™ Calcium directly represent the algorithm’s (device's) performance without human intervention in the measurement process. The CARESIDE Analyzer™ automatically performs the analysis.

7. Type of Ground Truth Used

The ground truth used for performance evaluation appears to be a "Reference Method."

For the method comparison, the document states: "CARESIDE™ = 0.90 (Reference Method) + 1.09 mg/dL, r = 0.95."
The "Reference Method for the predicate device is explicitly stated as "Atomic Absorption Spectrophotometry," and for the CARESIDE™ Calcium, it's "2-cresolphthalein complexone colorimetric." While the document doesn't explicitly state that the CARESIDE™ Calcium was compared against Atomic Absorption Spectrophotometry (which is generally considered a gold standard for calcium), it refers to a "Reference Method" in its method comparison, which implies a highly accurate and accepted laboratory method.

8. Sample Size for the Training Set

The document does not provide any information regarding a "training set" or its sample size. For an in vitro diagnostic device like this, the calibration information is bar-coded on each cartridge and may change with each lot, implying a manufacturing and calibration process rather than a machine learning "training set" in the common sense.

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

Since no training set information is provided or explicitly indicated as being part of an AI model in the modern sense, the method for establishing its ground truth is not applicable based on the provided text. The device uses "lot-specific standard curve to calculate calcium concentration," which implies a traditional calibration process rather than machine learning model training based on a labeled training set.

Summary

{0}------------------------------------------------

CARESIDE, Inc.

Page 13

CARESIDE™ Calcium (K983789) Premarket Notification Addendum December 11, 1998

K983789

Attachment 3: Revised 510(k) Summ

510(K) SUMMARY: CARESIDE™ CALCIUM SAFETY AND EFFECTIVENESS 1

I. Applicant Information

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

Device Information II.

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

D. Special controls and performance standards

111. Substantial Equivalence Claim

General equivalency claim A.

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

Calcium in vitro diagnostic products, in both dry film and other formats, are already on the U.S. market, including calcium products that utilize and dye reactions.

B. Specific equivalency claim

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

Name of Predicate Device:

Predicate Device 510K number: Product Code:

Johnson and Johnson's (formerly Eastman Kodak, Inc.) Vitros Ca DT Slides for Johnson and Johnson's Vitros DTSC II (formerly Eastman Kodak's DTSC II).

K912844/A 75CJY

CARESIDE, Inc. 6100 Bristol Parkway

Culver City, CA 90230 310-338-6767 Kenneth B. Asarch, Pharm.D., Ph.D. 310-338-6789 AsarchK@CARESIDE.com December 11, 1998

CARESIDE™ Calcium
Calcium test system Clinical chemistry panel Calcium test system Regulation Number: 21 CFR 862.1145 Regulatory Class II Classification Number: 75CJY None applicable

{1}------------------------------------------------

CARESIDE, Inc. Page 14

IV. Device Description

Explanation of Device Function A.

Each CARESTDE™ Calcium cartidge consists of a calcium-specific multi-layer reagent film mounted in a plastic base with a hinged lid. The user introduces the 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°C, and spins the cartridge to move the sample from the sample deposition well into the cartridge channels and chambers. 8.5uL of sample remains 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 spreading layer distributes the sample evenly on the film, and the sample moves through a reagent layer and a detection layer where a dye complex forms in the presence of calcium. The color intensity of the resulting blue dye, as measured by the amount of reflected light at 615 nanometers directly relates to the calcium concentration of the specimen.

Test Reaction Sequence: Ca + Bound-Ca -> Ca +2 Ca-2 + chlorophosphonazo (III) -> Ca-chlorophosphonazo (III)

As the cartidges spin, a photodiode measures reflectance of light emitted by 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 calcium concentration.

B. Test Summary

Calcium is an element found in fairly fixed proportions in the mineral phase of the human hard tissues (bone, dentine, and enamel) as well as in dynamic exchange with the intracellular and extracellular tissue fluids. Over 95% of the body calcium store is in the skeleton and tecth. Of the blood calcium, 45-50% is ionized, 40-45% is protein-bound and about 10% is chelated with ligands like citrate, lactate, phosphate and bicarbonates".

Intracellularly, calcium (Ca 1) is a prime inorganic messenger for cell function regulation, Extracellular Cat2 at the cell surface controls secretions from several endocrine glands including the parathyroid and pancreas. Calcium also plays a key role in blood coagulation.

The three main regulators of calcium homeostasis are parathyroid hormone, vitamin D, and calcitonin. Disorders involving these regulators directly impact calcium levels. Calcium level determination in human body fluids is used to measure parathyroid function, to assess vitamin D status; to evaluate calcium metabolism; to diagnose Addison's disease and to investigate malignancies . Increased calcium levels are seen in cases of hyperparathyroidism and malignancy. Reduced levels are commonly seen in cases of hypoalbuminemia

{2}------------------------------------------------

CARESIDE, Inc. Page 15

CARESIDE™ Calcium (K983789) Premarket Notification Addendum December 11, 1998

Intended Use V.

A. Intended Use
The CARESIDE™ Calcium cartridge is intended for in vitro diagnostic use in conjunction with the CARESIDE Analyzer™ to quantitatively measure calcium concentration in heparinized whole blood, heparin plasma, or serum.

B. Indications for Use

For in vitto diagnostic use with the CARESIDE Analyzer™ to quantitatively mensure total calcium from heparinized whole blood, heparin plasma or serum specimens to aid in diagnosis and treatment of patients with parathyroid disease, a variety of bone diseases, chronic renal disease, and tetany. It is intended for professional laboratory use: not for point of care or physician office laboratory use.

VI. Technological Characteristics

Similarities A.

	CARESIDE™ Calcium	Vitros CA DT Slides
Intended Use	Primarily to aid in the diagnosis and treatment of patients with parathyroid disease, a variety of bone diseases, chronic renal disease, and tetany (intermittent muscular contractions or spasms).	Same
Indications	For in vitro diagnostic use.For professional laboratory:not for point of care orphysician office laboratory use.	For in vitro diagnostic use
Measurement	Quantitative	Same
Method Principle	Dry film based already on the U.S. market, including calcium products that utilize azo dye reactions.	Same
Specimen	Not required	Same
Materials	Chlorophosphonazo (III)	Arsenazo (III) dye
Detector	Reflectance (615)	Reflectance (680 nm)
Test time	Approx. 4-minute warm-up(on-board) plus 4 minute testtime.	15 minutes slide warm-up(off-line) plus 5 minutes testtime.
Reference Method	2-cresolphthalein complexonecolorimetric	Atomic AbsorptionSpectrophotometry
Sample Type	Heparinized whole blood,heparin plasma or serum	Same
Specimen volume	8.5 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 DTSC IIcalibrators whenever a newslide lot is used or whennecessary.
Quality Control	2 levels	Same
Reporting Units	mg/dL or mmol/L	Same
Reaction Temp.	37 °C	Same

{3}------------------------------------------------

CARESIDE, Inc. Page 16

CARESIDE™ Calcium (K983789) Premarket Notification Addendum December 11, 1998

B. Differences

	CARESIDE™ Calcium	Vitros CA DT Slides
Specimen pre-treatment	Required	Required
Reportable range	4.2 to 14 mg/dL	3 to 14 mg/dL
Accuratepipetting	Not required	Required
Reagent pre-warming	Not required	Required

Comparative Performance Characteristics C.

	CARESIDE™ Calcium	Vitros Ca DT Slides
Detection limit	4.2 mg/dL	3 mg/dL
Reportable range	4.2 to 14 mg/dL	3 to 14 mg/dL
Accuracy	Mean recovery 98%	Not provided
Precision	Total CV at 6.5mg/dL, 7.8%	Total CV at 11.9 mg/dL = 1.6%
Method comparison	CARESIDE™ = 0.90 (Reference Method) + 1.09 mg/dL, r = 0.95
Linearity	Linearity yielded slope and correlation coefficient within acceptable limits.	Not provided
Interference	No significant interference observed at tested concentration of interferent:Ascorbic Acid, 10 mg/dLBilirubin, 10 mg/dLHemoglobin, 250 mg/dLMagnesium 2.5 mmol/LTriglycerides 600 mg/dL	Not provided

Conclusion D.

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

{4}------------------------------------------------

DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/4/Picture/2 description: The image is a black and white logo for the Department of Health & Human Services - USA. The logo is circular with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter of the circle. In the center of the circle is a stylized image of an eagle.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

DEC 1 7 1998 Kenneth B. Asarch, Pharm. D., Ph.D. Vice President Quality Systems and Regulatory Affairs CARESIDE, Inc. 6100 Bristol Parkway Culver City, California 90230

Re: K983789 CARESIDE™ Calcium for use on the CARESIDE Analyzer™ Trade Name: Regulatory Class: II Product Code: CJY Dated: October 26, 1998 Received: October 27, 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 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). 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 Requlations, Title 21, Parts 800 A substantially equivalent determination assumes compliance to 895. with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General requlation (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 requlatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. 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 regulations.

{5}------------------------------------------------

Page 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 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.qov/cdrh/dsma/dsmamain.html".

Sincerely yours,

Steven Sutman

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

{6}------------------------------------------------

VI. INDICATIONS FOR USE

510(k) Number:

K983789

Device Name:

CARESIDE™ Calcium

For in vitro diagnostic use with the CARESIDE Analyzer™ to measure total Indications for use: calcium from heparinized whole blood, heparin plasma or serum specimens to aid in the diagnosis and Catchin from nepartnized whole brood, nepa a variety of bone diseases, chronic renal disease, and tetany. u catinent of pations with paraly of ences, at for point of care or physician office laboratory use.

(Division Sign-Off)
---------------------

Divi al Labora vices

510(k) Number	K983789
---------------	---------

(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

§ 862.1145 Calcium test system.

(a)
Identification. A calcium test system is a device intended to measure the total calcium level in serum. Calcium measurements are used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany (intermittent muscular contractions or spasms).(b)
Classification. Class II.