The intended use for the N-ASSAY Glu-UL Reagent is for the quantitative determination of glucose in serum, plasma, urine, and cerebrospinal fluid in the diagnosis and treatment of diabetes mellitus, neonatal hypoglycemia and idiopathic hypoglycemia, and of pancreatic islet cell carcinoma. For in vitro diagnostic use only.

Device Description

The N-ASSAY Glu-UL reagent is based on an enzymatic hexokinase/glucose-6phosphate dehydrogenase method, shows good correlation with similar glucose reagents, practically no interference by coexistent substances, high sensitivity with good reproducibility, wide assay range, and is a convenient ready-to-use liquid type reagent.

In this method, serum D-glucose is phosphorylated by hexokinase (HK) in the presence of adenosine triphosphate (ATP) to produce glucose-6-phosphate (G-6-P) and adenosine diphosphate (ADP). Glucose-6-phosphate dehydrogenase (G-6-PDH) 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 nm (sub) and can be detected spectrophotometrically. The increase in absorbance measured at 340 nm (main) and 405 (sub), due to the formation of the NADPH, is directly proportional to the glucose concentration in the sample.

AI/ML Overview

The provided text describes a 510(k) submission for the N-ASSAY Glu-UL (Glucose Assay Reagent). It details the device's function and provides comparison studies against predicate devices to demonstrate substantial equivalence.

Here's an analysis of the acceptance criteria and study information:

1. Table of Acceptance Criteria and Reported Device Performance

The submission does not explicitly state pre-defined acceptance criteria in terms of specific thresholds for correlation coefficients or regression equations. Instead, it demonstrates "substantial equivalence" to predicate devices, implying that the performance must be comparable to these already marketed devices.

Acceptance Criteria (Implied by Substantial Equivalence to Predicate)	Reported Device Performance	Comments
Serum Samples: Performance comparable to Medical Analysis Systems Glucose liquid reagent (K853464)	Correlation coefficient: 0.99587	High correlation indicates strong agreement.
	Regression equation: y = 0.8861x + 4.7012	The slope and intercept suggest a slight difference in absolute values compared to the predicate, but with a strong linear relationship.
Precision acceptable on a day-to-day basis	Precision studies indicate acceptable values	No specific metrics for "acceptable" are provided.
Minimum detectable level comparable to predicate	Minimum detectable level: 1 mg/dl	No direct comparison to the predicate's MDL is given, but 1 mg/dl is stated.
Linearity comparable to predicate	Linear to 1,000 mg/dl	No direct comparison to the predicate's linearity range is given, but 1,000 mg/dl is stated.
Urine Samples: Performance comparable to Boehringer Mannheim Glucose assay (K812303)	Correlation coefficient: 0.9989	High correlation indicates strong agreement.
	Regression equation: y = 1.038x + 1.528	The slope close to 1 and small intercept suggest good agreement with the predicate.
Limit of quantitation comparable to predicate	Limit of quantitation: 0.3 mg/dl	No direct comparison to the predicate's LOQ is given, but 0.3 mg/dl is stated.
CSF Samples: Performance comparable to Boehringer Mannheim Glucose assay (K812303)	Correlation coefficient: 0.9923	High correlation indicates strong agreement.
	Regression equation: y = 1.080x + -1.233	The slope close to 1 and small intercept suggest good agreement with the predicate.
Limit of quantitation comparable to predicate	Limit of quantitation: 0.3 mg/dl	No direct comparison to the predicate's LOQ is given, but 0.3 mg/dl is stated.

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

The document does not explicitly state the sample sizes used for the comparison studies for serum, urine, or CSF samples. It only mentions "serum samples," "urine samples," and "CSF samples" in a general sense.

The data provenance is not explicitly mentioned (e.g., country of origin, retrospective or prospective). However, given the context of a 510(k) submission for a diagnostic reagent, it is highly likely these were prospective laboratory studies.

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

This information is not applicable in this context. The "ground truth" for a quantitative diagnostic reagent like N-ASSAY Glu-UL is typically established by:

Reference Methods: Highly accurate and precise laboratory methods.
Predicate Device Results: The results obtained from the legally marketed predicate devices are used as the comparative "truth" to assess the performance of the new device.

There were no human experts evaluating images or making diagnoses against which the device's output would be compared.

4. Adjudication Method for the Test Set

This information is not applicable. Since the "ground truth" is established by reference methods or predicate device results, there is no need for expert adjudication. The comparison is made directly between the quantitative results of the new device and the predicate device.

5. 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 information is not applicable. An MRMC study is relevant for diagnostic imaging devices where human readers interpret images, often with and without AI assistance. The N-ASSAY Glu-UL is a chemical reagent for quantitative blood and fluid analysis, not an imaging device.

6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done

The studies described are inherently "standalone" in the sense that they evaluate the performance of the reagent itself (which is analogous to an "algorithm" in a chemical assay) against predicate methods. There is no "human-in-the-loop" aspect being evaluated in these comparison studies; the studies assess how well the reagent performs in generating quantitative results.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

The ground truth used for the comparison studies was the results obtained from the predicate devices:

For serum samples: Medical Analysis Systems Glucose liquid reagent (K853464)
For urine and CSF samples: Boehringer Mannheim Glucose assay (K812303)

These predicate devices are themselves established glucose measurement methods.

8. The sample size for the training set

The document does not provide information on a "training set" for the N-ASSAY Glu-UL reagent. This is because the device is a chemical reagent, not a machine learning or AI-based system that typically requires a training set. The performance is based on the chemical reactions and optical detection, which are inherent properties of the reagent's formulation.

9. How the ground truth for the training set was established

As there is no mention of a "training set" for this chemical reagent, this information is not applicable. The ground truth for evaluating the reagent's performance (as described in point 7) was established by comparing its results to established predicate methods.

Summary

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SEP 3 1998

CRESTAT DIAGNOSTICS, INC.

K980883

25549 Adams Avenue Murrieta, CA 92562

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:

March 2, 1998 Date:

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

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

N-ASSAY Glu-UL (Glucose Assay Reagent) Product:

Blood qlucose determinations are one of the most frequently performed clinical chemistry laboratory procedures and are commonly used as an aid in the diagnosis and treatment of diabetes. Early methods were based on the reducing properties of glucose: however, these methods are susceptible to positive errors caused by nonglucose-reducing substances present in normal blood. Chemical methods using otoluidine offered improved specificity, but other sugars not normally present in serum can also react with o-toluidine and be a potential source of error. Enzymatic methods using purified enzymes which act on glucose provided greater specificity.

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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 Glu-UL Reagent is demonstrated by its substantial equivalence to the Medical Analysis Systems Glucose liguid reagent (K853464) which is also based on an enzymatic hexokinase/glucose-6phosphate dehydrogenase method. Both test systems are intended to quantitatively measure glucose in human serum.

In comparison studies against the predicate assay, a correlation coefficient of 0.99587 and a regression equation y = 0.8861 x + 4.7012 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 mg/dl. The N-ASSAY Glu UL reagent is linear to 1,000 mg/dl.

For urine and CSF samples, the liquid Crestat N-ASSAY Glu-UL Reagent was compared to the Boehringer Mannheim Glucose assay (K812303) which is also based on an enzymatic hexokinase method. Using urine samples, a correlation coefficient of 0.9989 and a regression equation y = 1.038 x + 1.528 was obtained. Using CSF samples, a correlation coefficient of 0.9923 and a regression equation of y = 1.080 x + -1.233 was obtained. The limit of quantitation is 0.3 mg/dl.

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Image /page/2/Picture/1 description: The image shows the seal of the Department of Health and Human Services (HHS). The seal features the HHS logo, which consists of a stylized caduceus with three snakes intertwined around a staff. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" are arranged in a circular pattern around the logo. The seal is black and white.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

SEP 3 1998

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

K980883 Re : N-ASSAY Glu-UL Requlatory Class: II Product Code: CFR June 30, 1998 Dated: Received: July 2, 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 reqistration, 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. ਉ 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 requlation 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 Litman

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

12980883 510(k) Number (if known): __

N-ASSAY Glu-UL (Glucose 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)

Cun

(Division Sign-Off) Division of Clinical Laborato 510(k) Number .

Prescription Use
(Per 21 CFR 801.109)

Over-The-Counter Use

Optional Format 1-2-96)

Regulation Number and Section

§ 862.1345 Glucose test system.

(a)
Identification. A glucose test system is a device intended to measure glucose quantitatively in blood and other body fluids. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, and idiopathic hypoglycemia, and of pancreatic islet cell carcinoma.(b)
Classification. Class II (special controls). The device, when it is solely intended for use as a drink to test glucose tolerance, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.