The intended use for the N-ASSAY CPK-L Reagent is for the quantitative determination of serum creatine phosphokinase (CPK) activity in human serum in the diagnosis and treatment of myocardial infarction and muscle diseases such as muscular dystrophy.

Device Description

The N-ASSAY CPK-L reagent is based on an optimized CPK kinetic method as recommended by the Japan Society of Clinical Chemistry, shows good correlation with similar CPK reagents, practically no interference by coexistent substances, high sensitivity with good reproducibility, wide assay range, and is convenient ready-to-use liquid type reagent. The N-ASSAY CPK-L reagent utilizes an enzymatic method. In this procedure, creatine phosphate is dephosphorylated by creatine phosphokinase (CPK) in the presence of adenosine disphosphate (ADP) to produce creatine and adenosine triphosphate (ATP). ATP is dephosphorylated by hexokinase in the presence of D-glucose to produce glucose-6-phosphate (G-6-P) and adenosine diphosphate. Glucose-6-phosphate dehydrogenase specifically oxidizes G-6-P to 6-phosphogluconate with the concurrent reduction of nicotinamide adenine dinucleotide phosphate (NADP) to nicotinamide adenine dinucleotide phosphate reduced (NADPH). The NADPH produced absorbs light at 340 nm (main) and 405 (sub) and can be detected spectrophotometrically. The increase per minute in absorbance measured at 340 nm (main) and 405 (sub), due to the formation of NADPH, is directly proportional to CPK activity in the sample.

AI/ML Overview

Here's an analysis of the provided text regarding the acceptance criteria and study for the CRESTAT N-ASSAY CPK-L Reagent:

Acceptance Criteria and Device Performance

The provided document describes the safety and effectiveness of the N-ASSAY CPK-L Reagent in relation to a predicate device, the Medical Analysis Systems CK liquid reagent (K781719). The acceptance criteria for this type of medical device are generally framed around demonstrating substantial equivalence to a legally marketed predicate device.

Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria Category	Specific Criteria	Reported Device Performance (N-ASSAY CPK-L)
Substantial Equivalence	Demonstrates comparable performance to a legally marketed predicate device (Medical Analysis Systems CK liquid reagent, K781719).	"demonstrated by its substantial equivalence to the Medical Analysis Systems CK liquid reagent (K781719) which is based on a similar method."
Correlation	A strong correlation with the predicate device for quantitative measurement of CPK in human serum.	"a correlation coefficient of 0.99965... was obtained with serum samples."
Regression Analysis	A regression equation indicating close agreement with the predicate device.	"a regression equation y = 0.9989 x + -0.3488 was obtained with serum samples." (Where 'y' is likely CPK-L and 'x' is the predicate device's result).
Precision	Acceptable day-to-day reproducibility of results.	"Precision studies indicate acceptable values can be obtained on a day to day basis."
Minimum Detectable Level	The lowest concentration of CPK the device can reliably detect.	"The minimum detectable level of this method is 1 IU/L."
Linearity/Assay Range	The range of CPK concentrations over which the device provides accurate and proportional results.	"The N-ASSAY CPK-L reagent is linear to 2,000 IU/L."

Study Details

The information provided describes a comparison study to demonstrate substantial equivalence to a predicate device.

Sample size used for the test set and the data provenance:
- Sample Size: The document mentions "serum samples" but does not specify the exact number of samples used in the comparison study.
- Data Provenance: The document does not specify the country of origin of the data. It does not explicitly state if the study was retrospective or prospective, but comparison studies for K510 submissions often involve collecting prospective samples or using banked samples.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This type of study (comparing a new in-vitro diagnostic reagent against a predicate reagent) does not typically involve human expert adjudication for image interpretation. The "ground truth" is established by the performance of the predicate device. Therefore, no information is provided on experts or their qualifications for establishing ground truth in this context.
Adjudication method for the test set:
- Not applicable as this is a comparison study between two in-vitro diagnostic reagents, not an interpretation task requiring expert adjudication.
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. This is not an AI-assisted diagnostic device, nor does it involve human readers interpreting cases. It is an in-vitro diagnostic reagent.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, implicitly. The performance metrics (correlation, regression, minimum detectable level, linearity, precision) are all derived from the performance of the reagent itself, a "standalone algorithm" in the context of an in-vitro diagnostic. There is no human-in-the-loop component for the measurement itself; the human only performs the assay.
The type of ground truth used:
- The "ground truth" in this context is the results obtained from the predicate device (Medical Analysis Systems CK liquid reagent, K781719). The study seeks to show that the new device's results are substantially equivalent to those of the predicate.
The sample size for the training set:
- The document does not explicitly describe a "training set" in the sense of modern machine learning. For an in-vitro diagnostic reagent, the "training" involves the development and optimization of the reagent formulation and assay parameters based on known chemical principles and experimental trials. The specific sample size for this development phase is not provided.
How the ground truth for the training set was established:
- Not directly applicable in the sense of a medical imaging or AI model "training set." The "ground truth" during the development of this chemical reagent would have been established through well-characterized reference materials, known concentrations of CPK, and established laboratory methods to ensure the reagent's components and reactions are functioning as expected to accurately measure CPK activity.

Summary

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CRESTAT DIAGNOSTICS, INC.

25549 Adams Avenue Murrieta, CA 92562

MAR 2 6 1998

510(K) SUMMARY OF SAFETY AND EFFECTIVENESS

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR § 807.92.

The assigned 510(k) number is: __ K 980500

March 2. 1998 Date:

Colin Getty Submitted by: KAMIYA BIOMEDICAL COMPANY 910 Industry Drive, Seattle WA 98188 TEL: 206-575-8068; FAX: 206-575-8094

For:

Crestat Diagnostics, Inc. 25549 Adams Avenue Murrieta, CA 92562

N-ASSAY CPK-L (Creatine Phosphokinase Assay Reagent) Product:

Creatine phosphokinase (CPK) is an enzyme primarily found in skeletal muscle, cardiac muscle and brain tissue. Elevated serum levels of CPK are associated with myocardial infarction, various muscle diseases, trauma, exercise, and acute cerebrovascular disease. Oliver described the first assay of CPK activity using creatine phosphate. Since then, this method has been modified and optimized by many individuals,

The N-ASSAY CPK-L reagent utilizes an enzymatic method. In this procedure, creatine phosphate is dephosphorylated by creatine phosphokinase (CPK) in the presence of adenosine disphosphate (ADP) to produce creatine and adenosine triphosphate (ATP). ATP is dephosphorylated by hexokinase in the presence of D-glucose to produce glucose-6-phosphate (G-6-P) and adenosine diphosphate. Glucose-6-phosphate dehydrogenase specifically oxidizes G-6-P to 6-phosphogluconate with the concurrent reduction of nicotinamide adenine dinucleotide phosphate (NADP) to nicotinamide adenine dinucleotide phosphate reduced (NADPH). The NADPH produced absorbs light at 340 nm (main) and 405 (sub) and can be detected spectrophotometrically. The increase per minute in absorbance measured at 340 nm (main) and 405 (sub), due to the formation of NADPH, is directly proportional to CPK activity in the sample.

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CRESTAT DIAGNOSTICS, INC.

510(K) SUMMARY OF SAFETY AND EFFECTIVENESS (Continued)

The safety and effectiveness of the liquid Crestat N-ASSAY CPK-L Reagent is demonstrated by its substantial equivalence to the Medical Analysis Systems CK liquid reagent (K781719) which is based on a similar method. Both test systems are intended to quantitatively measure CPK in human serum.

In comparison studies against the predicate assay, a correlation coefficient of 0.99965 and a regression equation y = 0.9989 x + -0.3488 was obtained with serum samples. Precision studies indicate acceptable values can be obtained on a day to day basis. The minimum detectable level of this method is 1 IU/L. The N-ASSAY CPK-L reagent is linear to 2,000 IU/L.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is circular and features the department's name in a ring around the outside. Inside the ring is an image of an eagle with its wings spread.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

MAR 26 1998

Crestat Diagnostics, Inc. C/O Colin Getty KAMIYA Biomedical Company 910 Industry Drive Seattle, Washington, 98188

Re : K980900 N-ASSAY CPK-L (Creatine Phosphokinase Assay Reagent) Requlatory Class: II Product Code: ପ୍ରତିଆରି ବିଧାନ ସଭାକୁ ନିର୍ବାଚନ ହେଇଥିଲେ । ପ୍ରତିଶତ ହେଇଥିଲେ । ପ୍ରତିଶତ ହେଇଥିଲେ । ପ୍ରତିଶତ ହେଇଥିଲେ । ପ୍ରତିଶତ ହେଇଥିଲେ । ପ୍ରତିଶତ ହେଇଥିଲେ । ପ୍ରତିଶତ ହେଇଥିଲେ । ପ୍ରତିଶତ ହେଇଥିଲେ । March 2, 1998 Dated: Received: March 10, 1998

Dear Mr. Getty:

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 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 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 Failure to Administration (FDA) will verify such assumptions. 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.qov/cdrh/dsmamain.html".

Sincerely yours,
Steven Bitman

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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INDICATIONS FOR USE STATEMENT

510(k) Number (if known): _ K 980900

N-ASSAY CPK-L (Creatine Phosphokinase Assay Reagent) Device Name:

Indications For Use:

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number	K980900

Prescription Use(Per 21 CFR 801.109)	✓
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Over-The-Counter Use
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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.