For in vitro diagnostic use with the CARESIDE Analyzer™ to quantitatively measure CK from anti-coagulated whole blood, plasma, or serum specimens to aid in the diagnosis and treatment of patients with myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy.

Device Description

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

AI/ML Overview

Here is a summary of the acceptance criteria and the study details for the CARESIDE™ CK device, based on the provided text:

Acceptance Criteria and Device Performance

Acceptance Criteria	CARESIDE™ CK Performance
Detection limit	20 U/L
Reportable range	20 to 1600 U/L
Accuracy	Mean recovery 101%
Precision	Total CV, 168 U/L, 10%
Linearity	Linearity yielded slope and correlation coefficient within acceptable limits.
Interference	No significant interference observed at tested concentrations of interferent: Ascorbic Acid, 10 mg/dL; Bilirubin, 20 mg/dL; Triglycerides 2000 mg/dL

Note: The provided document does not explicitly state pre-defined "acceptance criteria" against which these performance metrics were tested, but rather reports the device's performance. The conclusion states that the data demonstrates the device "performs as well as or better than the legally marketed predicate device," implying these results met the necessary thresholds for substantial equivalence to the predicate (Vitros CK DT Slides). The predicate device's specific values for Accuracy, Linearity, and Reference Method are not provided for direct comparison, but the detection limit and reportable range are identical.

Study Details

Sample sizes used for the test set and the data provenance:
- The document does not specify the sample size used for the test set (e.g., for accuracy, precision, linearity, or interference studies).
- The data provenance (e.g., country of origin, retrospective or prospective) is also not specified.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The document does not mention the use of experts or their qualifications for establishing ground truth in the context of the device's performance evaluation. The reference method used for comparison is a "Kinetic determination with enzymatically coupled spectrophotometric detection of creatine." This suggests a laboratory-based method of higher accuracy was used as the ground truth.
Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- No adjudication method is described. The performance is reported against a "Reference Method."
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:
- This is a diagnostic device for measuring Creatine Kinase (CK) activity, not an AI-assisted imaging or diagnostic tool that involves "human readers." Therefore, an MRMC comparative effectiveness study involving human readers or AI assistance in that context is not applicable and was not performed.
If a standalone (i.e., algorithm only without human-in-the loop performance) was done:
- Yes, the performance characteristics (detection limit, reportable range, accuracy, precision, linearity, interference) are reported for the CARESIDE™ CK device as a standalone analytical instrument. This device is an in vitro diagnostic test system; its performance metrics describe the algorithm/device's ability to measure CK activity independently.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The ground truth for accuracy and method comparison was established using a "Reference Method: Kinetic determination with enzymatically coupled spectrophotometric detection of creatine." This is a laboratory-based analytical method considered highly accurate for CK measurement.
The sample size for the training set:
- The document does not mention a "training set" in the context of device development. This device is a chemical assay system, not a machine learning model that typically requires a separate training set. Its calibration is mentioned as "bar-coded on each cartridge" and "may change with each lot," indicating a manufacturer-defined calibration rather than a trained algorithm.
How the ground truth for the training set was established:
- As no "training set" is described for this type of device, this question is not applicable. The device relies on a pre-defined chemical reaction and established spectrophotometric principles for its measurement and calibration.

Summary

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4/19/99

CARESIDE, Inc.

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510(K) SUMMARY: CARESIDE™ CK SAFETY AND IV. EFFECTIVENESS

I. Applicant Information

A. Applicant Name
Applicant/Manufacturer Address B.
C. Telephone Number
D. Contact Person
E. FAX Number
F. e-Mail Address
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@CARESIDE.com January 29, 1999

CARESIDE™ CK

Creatine phosphokinase/creatine kinase or isoenzymes test system Clinical chemistry panel CK test system Regulation Number: 21 CFR 862.1215 Regulatory Class II Classification Number: 75JFX None applicable

D. Special controls and performance standards

III. Substantial Equivalence Claim

General equivalency claim A.
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.

CK in vitro diagnostic products, in both dry film and other formats, are already on the U.S. market, including CK products that utilize enzymatic coupling to convert the reaction product, ATP, to a colored dye.

B. Specific equivalency claim

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

Name of Predicate Device:	Johnson and Johnson's (formerly Eastman Kodak, Inc.) Vitros CK DT Slides for use on theVitros DTSC module of the Virtos DT II system(formerly Eastman Kodak's DT 60 II).
Predicate Device 510K number:	K912844/A
Product Code:	75JFX

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IV. Device Description

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

Explanation of Device Function A.

Fach CARESIDE™ CK cartridge consists of a CK-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. 8.5 µL microliters of sample remains in the metering passage. Any excess sample flows into an overflow well.

The sample is automatically dispensed onto the multi-layer reagent film. The spreading and substrate layer distributes the specimen which in turn catalyzes the reaction of creatine phosphate with ADP to form creatine and ATP. In the reagent layer, glucose-6phosphate (G-6-P) is formed by the hexokinase catalyzed reaction of glucose with ATP. G-6-P then reduces NAD+ to NADH in a glucose 6-phosphate dehydrogenase (G6PDH) catalyzed reaction. NADH then reduces NTB to diformazan dye in a diaphorase catalyzed reaction. The color intensity of the resulting reddish dye, as measured by the amount of reflected light at 570 nanometers directly relates to the CK activity of the specimen.

Test Reaction Sequence:

Creatine phosphate + ADP - CPK -> Creatine + ATP Hexokinase > ADP + G-6-P ATP + Glucose Mg+2 G-6-P + NAD* -- Gepul-> 6-phosphogluconic acid + NADH + H* NTB + NADH -- Diaphorase > Diformazan dye + NAD*

As the cartridges spin, a photodiode measures reflectance of light emitted by a wavelength-specific light emitting diode (LED) over a fixed time period. The analyzer uses the reflectance measurements and the lot-specific standard curve to calculate CK activity.

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B. Test Summary

Creatine kinase (CK), also known as creatine phosphokinase, is an enzyme consisting of two sub-units (termed B and M) that catalyzes the reversible phosphorylation of creatine by adenosine-triphosphate (ATP) to creatine phosphate and adenosine-diphosphate (ADP). Only the CK dimer has enzymatic activity. Thus, total active CK is the combination of CKBB, CKMB and CKMM isoenzymes. These are also referred to as CK-1, CK-2 and CK-3 respectively, according to their differential mobility on an electrophoretic gel. CK is distributed in various organs; the highest activities are found in skeletal muscle, heart, and brain. Considerably lower activities are present in the urinary bladder, stomach, ileum, colon, and uterus. The CK content of liver, erythrocytes, and kidney is less that 1% of the amount found in skeletal muscle.

Measurement of total CK activity is important in the diagnosis of cardiac and skeletomuscular disorders, and is increased after muscle trauma, intramuscular injections, exercise, and in other conditions. CK level is also increased after acute alcohol intoxication, surgery-induced muscle injury, drug overdoses and poisoning, trauma to muscle or brain, hypothermia, hyperthermia, Reye's syndrome, infectious diseases, and hypothyroidism. Abnormal CK activities have been described in all forms of muscular dystrophy as well as polymyositis, dermatomyositis, and other myopathies. Many non-affected carriers of muscular dystrophy have abnormal CK activity in the blood. which provides a method for identifying such carriers.

V. Intended Use

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

B. Indications for Use

For in vitro diagnostic use with the CARESIDE Analyzer™ to quantitatively measure CK activity from anti-coagulated whole blood, plasma, or serum specimens to aid in the diagnosis and treatment of patients with myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy. It is intended professional laboratory use: not for point of care or physician office laboratory use.

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VI. Technological Characteristics

A. Similarities

	CARESIDE™ CK	Vitros CK DT Slides
Intended Use	Primarily to aid in the diagnosis	Diagnosis of skeletal muscle
	and treatment of patients with	disease, myocardial infarction,
	with myocardial infarction	and cerebrovascular accidents.
	and muscle diseases such as
	progressive, Duchenne-type
	muscular dystrophy.
Indications	For in vitro diagnostic use.	For in vitro diagnostic use
	For professional laboratory:
	for point of care ornot
	physician office laboratory use.
Measurement	Quantitative	Same
Method Principle	Reflectometry of enzymaticallycoupled production of dye from	Same
	CK reaction product.
Specimen dilution	Not required	Same

Materials	Creatine phosphate,	Glycerophosphate oxidase,peroxidase, gycerol kinase,
	nitrotetrazorium blue, ADP,	creatine phosphate,
	glucose, hexokinase, glucose-	N-acetylsysteine, magnesium
	6-phosphate dehydrogenase	acetate, glycerol, ADP.
	(G6PDH), NAD*, diaphoraseReflectance (570 nm)
Detector		Reflectance (680 nm)
Test time	Approximately4-minutewarm-up (on-board)plus	15 minutes slide warm-up
	4 minute test time.	(off-line) plus 5 minutes testtime.
Sample Type	Anti-coagulatedwhole blood,	Plasma or serum
	plasma, or serum
Specimen volume	8.5 ul test volume	10 µl
	(85 ± 15 ul applied volume)
Calibration	Calibrationinformation	Run Vitros DT II calibrators
	bar-coded on each cartridge.	whenever a new slide lot is
	Calibration informationmay	used or when necessary.
	change with each lot.
Quality Control	2 levels	Same
Reporting Units	U/L	Same
Reaction Temp.	37°C	Same

B. Differences

	CARESIDE™ CK	Vitros CK DT Slides
Accuratepipetting	Not required	Required
Reagentpre-warming	Not required	Required

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: ・・・

C. Comparative Performance Characteristics

	CARESIDE™ CK	Vitros CK DT Slides
Detection limit	20 U/L	20 U/L
Reportable range	20 to 1600 U/L	20 to 1600 U/L
Accuracy	Mean recovery 101%	Not provided
Precision	Total CV, 168 U/L, 10%	Total CV, 175 U/L, 3%
Reference Method	Kinetic determination withenzymatically coupledspectrophotometric detection ofcreatine.	Not provided
Methodcomparison	CARESIDE™ CK = 1.03 (Trace) – 22.4 U/L, r = 0.98
Linearity	Linearity yielded slope andcorrelation coefficient withinacceptable limits.	Not provided
Interference	No significant interferenceobserved at testedconcentration of interferent:Ascorbic Acid, 10 mg/dLBilirubin, 20 mg/dLTriglycerides 2000 mg/dL	Elevated carbon dioxide(> 40mmol/L) may decreaseCK results.

D. Conclusion

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

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Image /page/5/Picture/1 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with three lines forming its body and wings. The eagle is enclosed within a circle, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged around the upper half of the circle.

Public Health Service

APR 1 9 1995

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

Kenneth B. Asarch, Pharm. D., Ph.D. Vice President, Quality Systems/ Regulatory Affairs Careside Inc. 6100 Bristol Parkway Culver City, California 90230

K990439 Re: Trade Name: CARESIDE™ CK Regulatory Class: II Product Code: JHS Dated: January 29, 1999 Received: February 11, 1999

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 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 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.

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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/cdrl/dsma/dsmamain.html".

Sincerely yours,

Steven Dutman

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 16

INDICATIONS FOR USE VI.

510(k) Number:

Device Name:

K 990439

CARESIDE™ CK

Indications for use:

Sean Cooper
(Division Sign-Off)
Division of Clinical Laboratory Devices
K99 0439

510(k) Number

(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

§ 862.1215 Creatine phosphokinase/creatine kinase or isoenzymes test system.

(a)
Identification. A creatine phosphokinase/creatine kinase or isoenzymes test system is a device intended to measure the activity of the enzyme creatine phosphokinase or its isoenzymes (a group of enzymes with similar biological activity) in plasma and serum. Measurements of creatine phosphokinase and its isoenzymes are used in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy.(b)
Classification. Class II.