For in vitro diagnostic use with the CARESIDE Analyzer™ to measure CK-MB from whole blood, serum or plasma specimens to aid in the diagnosis and treatment of patients with myopathic disorders including myocardial infarction, myocarditis, Duchenne's muscular dystrophy, polymyosititis, and rhabdomyolysis.

Device Description

CARESIDE™ CKMB cartridges are used with the CARESIDE, Inc. CARESIDE Analyzer™ to measure CK-MB activity in whole blood, serum or plasma specimens. The CARESIDE™ CKMB 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-MB activity. The film cartridge (patent pending) contains all reagents necessary to measure CK-MB activity.

Each CARESIDE™ CKMB cartridge consists of a CK-MB-specific multi-layer reagent film mounted in a plastic base with a hinged lid. The user introduces the specimen into the cartridge Sample 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 Well into the cartridge channels and chambers. 8.5 uL of sample remains in the metering passage. Any excess sample flows into an overflow well.

The sample is automatically dispensed onto the multi-laver reagent film. The spreading layer distributes the specimen uniformly. In this layer CK-M activity is inhibited by the anti-CK-M subunit antibody contained in the layer. The CK-B subunit is not inhibited by the antibody but rather is activated by N-acetylcysteine. The CK-B activity is stoichometrically related to the CK-MB activty. The CK-B catalyzes the reaction of creatine phosphate with ADP, producing creatine and ATP. ATP reacts with endogenous glucose in a hexokinase-catalyzed reaction to produce glucose-6-phosphate and ADP. G-6-P is then oxidized by glucose-6-phosphate dehydrogenase producing nicotinamide adenine dinucleotide (NADH). NADH reduces nitrotetrazolium blue in a diaphorase catalyzed reaction, producing a diformazan dye. The rate of change of the color intensity of the resulting reddish dye, as measured by the amount of reflected light at 570 nanometers, directly relates to the specimen CK-MB activity.

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-MB activity.

AI/ML Overview

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

Acceptance Criteria and Device Performance

Acceptance Criteria	CARESIDE™ CKMB Reported Performance	Predicate Device (Vitros CKMB DT Slides)
Detection Limit	5 U/L	1 U/L
Reportable Range	5 to 300 U/L	1 to 300 U/L
Accuracy	Mean recovery 103%	Not provided
Precision	Total CV, 147 U/L, 10%	Total CV, 105 U/L, 4%
Method Comparison	CARESIDE™ = 1.00 (Paragon) - 8.9 U/L, r = 0.98 (This indicates a good correlation with the Paragon method, with the predicate not provided for this specific direct comparison)	Not provided (The "Paragon" likely refers to a reference or alternative method for comparison, not the predicate device itself in this context)
Linearity	Linearity yielded slope and correlation coefficient within acceptable limits.	Not provided
Interference	No significant interference observed at tested concentration of interferent: Ascorbic acid 5 mg/dL, Bilirubin 20 mg/dL	Various, see package insert

Study Information

Sample Size Used for the Test Set and Data Provenance:
- Test Set Sample Size: Not explicitly stated in the provided text. The "Method comparison" section mentions "CARESIDE™ = 1.00 (Paragon) - 8.9 U/L, r = 0.98," which implies a comparison study was performed, but the number of samples used for this correlation is not provided.
- Data Provenance: Not specified (e.g., country of origin, retrospective or prospective).
Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts: Not applicable. This device is an in vitro diagnostic (IVD) for quantitative measurement of a biomarker, not an interpretative AI device requiring expert adjudication of images or signals. The "ground truth" for its performance is typically established by comparison to reference methods or validated laboratory measurements.
Adjudication Method for the Test Set: Not applicable for this type of IVD device.
If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done: No, this is not an MRMC study. MRMC studies are typically for medical image analysis or diagnostic interpretation by human readers, often comparing performance with and without AI assistance. This device is a quantitative diagnostic test.
If a Standalone Performance Study Was Done: Yes, a standalone performance study was conducted. The "Comparative Performance Characteristics" section directly reports the CARESIDE™ CKMB's performance metrics (detection limit, reportable range, accuracy, precision, linearity, interference) independently, and then compares them against the predicate device where possible. The method comparison with "Paragon" also represents a standalone assessment against an established method.
The Type of Ground Truth Used:
- For Method Comparison: The device's results were compared against an unstated "Paragon" method (likely an established laboratory reference method).
- For Reference Method: The text states the reference method for % CKMB was "Electrophoresis for % CKMB in combination with kinetic spectrophotometric determination of total CK." This is what would be considered the "ground truth" or gold standard for validating the CK-MB measurements.
The Sample Size for the Training Set: Not applicable. This device is an in vitro diagnostic assay, not an AI/ML model that requires a "training set" in the conventional sense. Its "training" is inherent in its chemical design and calibration process.
How the Ground Truth for the Training Set Was Established: Not applicable. As an IVD assay, its accuracy relies on the validated chemical reactions and calibration materials rather than a "training set" with established ground truth labels. Calibration information is "bar-coded on each cartridge" and can change with each lot, indicating internal validation processes.

Summary

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4/19/99

CARESIDE, Inc.
Page 10

R990134

CARESIDE™ CKMB Premarket Notification
January 29, 1999

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

Applicant Information I.

Applicant Name A.
Applicant/Manufacturer Address B.
Telephone Number C.
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™ CKMB

CK-MB test system Clinical chemistry panel CK-MB test system Regulation Number: 21 CFR 862.1215 Regulatory Class II Classification Number: to be assigned None applicable

D. Special controls and performance standards

Substantial Equivalence Claim III.

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.

CK-MB in vitro diagnostic products, in both dry film and other formats, are already on the U.S. market, including CK-MB products which are based upon immunoinhibition.

B. Specific equivalency claim

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

Name of Predicate Device:	Johnson and Johnson's (formerly Eastman Kodak, Inc.) Vitros CKMB Slides for Johnson and Johnson's Vitros DTSC module of the Vitros DT II system (formerly Eastman Kodak's DTSC 60 II).
Predicate Device 510K number:	K912844/A
Product Code:	unknown

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IV. Device Description

Explanation of Device Function A.

Test Reaction Sequence:

Anti –CK –M antibody СК-ММ. СК-МВ > CK-B

CK-B Creatine phosphate + ADP Creatine + ATP NAC Mu-2

Hexokinase > ADP + G-6-P ATP + Glucose Mg "

G6PDH G-6-P + NAD* > 6-phosphogluconic acid + NADH + H*

Diaphorase > Diformazan dye + NAD* NTB + NADH -

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B. Test Summary

Creatine kinase (CK) 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, active CK occurs as 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.

Each CK isoenzyme is found in a particular tissue. CKBB (CK-1) is found in the brain, prostate, gut, lung, bladder, uterus, placenta and thyroid. CKMB (CK-2) is found in the heart muscle and CKMM (CK-3) is found in skeletal and cardiac muscle. Thus, the measurement of CK and its various isoenzymes is important in the diagnosis of several diseases, especially in myocardial infarction.

In myocardial infarction, the first 4 to 6 hours are characterized by a rise in the total CK activity. reaching a peak value between 18 and 30 hours and returning to normal by the third day. This rise is followed by a rise of the CKMB (CK-2) fraction, which reaches a maximum about 12-14 hours after a myocardial infarction. It should be noted that CKMB (CK-2) breaks down faster then CKMM (CK-3), and so may return to normal levels 48-72 hours post-infarction. CKMB levels are used as an indication and measure of myocardial damage. Other cardiac conditions such as angina pectoralis, cardiogenic shock, electrical countershock, tachycardia, myocarditits and congestive heart failure have been reported as having a low occurrence of elevated total CK and CKMB (CK-2). Cardiac trauma resulting from heart surgery will cause an elevation in total CK and CKMB (CK-2) so as to mask elevations subsequent to intraoperative myocardial infarction.

V. Intended Use

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

B. Indications for Use

This product is indicated for use in the diagnosis and treatment of patients with myopathic disorders including myocardial infarction, myocarditis, Duchenne's muscular dystrophy, polymyosititis, and rhabdomyolysis.

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VI. Technological Characteristics

A. Similarities

Similarities
	CARESIDETM CKMB	Vitros CKMB DT Slides
Intended Use	Primarily to aid in the diagnosisand treatment of patients withmyopathic disorders includingmyocardial infarction,myocarditis, Duchenne'smuscular dystrophy,polymyosititis, andrhabdomyolysis.	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 immunoinhibitorymethod using reflectancephotometry for signal detection.	Same
Specimen dilution	Not required	Same
Key Materials	Goat anti-human CK-Mpolyclonal antibody	Goat anti-human CK-Mpolyclonal antibody
Detector	Reflectance (570 nm)	Reflectance (680 nm)
Test time	Approximately 4 minuteswarm-up (on-board) plus5 minutes test time.	15 minutes slide warm-up(off-line) plus 5 minutes testtime.
Sample Type	Anti-coagulated whole blood,serum, or plasma	Serum and Plasma
Specimen volume	8.5 µl test volume(85 ± 15 µl applied volume)	10 µl
Calibration	Calibration informationbar-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	U/L	Same
Reaction Temp.	37 °C	Same

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......

B. Differences

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

C. Comparative Performance Characteristics

	CARESIDE™ CKMB	Vitros CKMB DT Slides
Detection limit	5 U/L	1 U/L
Reportable range	5 to 300 U/L	1 to 300 U/L
Accuracy	Mean recovery 103%	Not provided
Precision	Total CV, 147 U/L, 10%	Total CV, 105 U/L, 4%
Reference Method	Electrophoresis for % CKMBin combination with kineticspectrophotometricdetermination of total CK	Not provided
Method comparison	CARESIDE™ = 1.00 (Paragon) - 8.9 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 5 mg/dLBilirubin 20 mg/dL	Various, see package insert

D. Conclusion

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

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Image /page/5/Picture/2 description: The image is a black and white seal for the Department of Health & Human Services - USA. The seal is circular with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized image of an eagle.

APR 1 9 1999

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

Re: K990434 Trade Name: CARESIDE™ CKMB 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/cdrh/dsma/dsmamain.html"

Sincerely yours,

Steven Putman

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 990434

CARESIDE™ CKMB

Indications for use:

Scaniogen

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K990434

(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.