The intended use for the N-ASSAY L D-BIL Reagent is for the quantitative measurement of direct bilirubin in human serum in the diagnosis and treatment of various liver diseases. For in vitro diagnostic use only.

Device Description

The N-ASSAY L D-BIL reagent is based on a chemical oxidation method, utilizing sodium nitrite as an oxidizing agent, shows good correlation with similar direct bilirubin reagents, practically no interference by coexistent substances, high sensitivity with good reproducibility, wide assay range, and is convenient ready-to-use liquid type reagent. In this method, a serum sample containing direct bilirubin is mixed with the reagent containing sodium nitrite. Direct billrubin is oxidized by nitrite at pH 3.7 to produce biliverdin which causes the absorbance at 450 nm (main) and 546 (sub), specific to bilirubin, to decrease. Therefore, the direct bilirubin concentration in the sample can be obtained by measuring the absorbance before and after the sodium nitrite oxidation.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the N-ASSAY L D-BIL (Direct Bilirubin Assay Reagent), based on the provided text:

Acceptance Criteria and Device Performance

Acceptance Criteria Category	Acceptance Criteria	Reported Device Performance
Correlation with Predicate	Not explicitly stated as a numerical AC, but generally implies a strong linear relationship.	Correlation coefficient of 0.98476 with predicate assay (WAKO Chemicals Direct Bilirubin liquid reagent). Regression equation: y = 1.0882 x + 0.1574.
Precision	Acceptable precision.	Precision studies indicate acceptable values can be obtained on a day-to-day basis.
Minimum Detectable Level	Not explicitly stated as a numerical AC.	Minimum detectable level of 0.05 mg/dl.
Linearity	Not explicitly stated as a numerical AC.	Linear to 20 mg/dl.
Interference by Coexistent Substances	Practically no interference by coexistent substances.	Shows practically no interference by coexistent substances.
Reagent Stability	Good reagent stability.	Good reagent stability.
Sensitivity	High sensitivity.	Shows high sensitivity.
Reproducibility	Good reproducibility.	Shows good reproducibility.
Assay Range	Wide assay range.	Shows wide assay range.
Convenience	Convenient ready-to-use liquid type reagent.	Is convenient ready-to-use liquid type reagent.

Study Details

2. Sample size used for the test set and the data provenance:

Sample Size: Not explicitly stated. The text mentions "serum samples" for the correlation study but doesn't provide the number of samples.
Data Provenance: Not explicitly stated. Given it's a 510(k) submission for a diagnostic device, the samples would typically be human serum. It's not specified if they were retrospective or prospective, nor their country of origin.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

Not applicable. This is not a study requiring expert interpretation of images or other qualitative data. The comparison is against a legally marketed predicate device using quantitative measurements.

4. Adjudication method for the test set:

Not applicable. This is not a study requiring adjudication of expert opinions. The comparison is analytical performance against a 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:

No. This is a 510(k) submission for an in vitro diagnostic reagent, not an AI-based imaging or analytical device that would involve human readers or AI assistance in interpretation.

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

Yes, implicitly. The performance metrics (correlation, precision, minimum detectable level, linearity) describe the analytical performance of the N-ASSAY L D-BIL reagent itself, without human intervention in the measurement process after sample introduction. It's a "device only" performance assessment.

7. The type of ground truth used:

The "ground truth" for the comparison study was the measurements obtained from the predicate device, the WAKO Chemicals Direct Bilirubin liquid reagent (K970986). The study aimed to demonstrate substantial equivalence by correlating the new device's results with the predicate's results.

8. The sample size for the training set:

Not applicable. This is a chemical reagent, not an algorithm that requires a training set in the sense of machine learning. The "development" would involve chemical formulation and optimization, not data training.

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

Not applicable, as there's no training set in the context of an algorithm.

Summary

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CRESTAT DIAGNOSTICS, INC.

981276

25549 Adams Avenue Murrieta, CA 92562

1 1998 MAY

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:

April 2, 1998 Date:

Colin Gettv Submitted bv: 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

Product: N-ASSAY L D-BIL (Direct Bilirubin Assay Reagent)
Serum bilirubin measurement is widely used as a screening test for liver functions. The diazo coupling method and bilirubin oxidase enzymatic method are widely used; however, these methods have disadvantages such as interference by coexistent serum substances and poor reagent stability.

In this method, a serum sample containing direct bilirubin is mixed with the reagent containing sodium nitrite. Direct billrubin is oxidized by nitrite at pH 3.7 to produce biliverdin which causes the absorbance at 450 nm (main) and 546 (sub), specific to bilirubin, to decrease. Therefore, the direct bilirubin concentration in the sample can be obtained by measuring the absorbance before and after the sodium nitrite oxidation.

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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 L D-BIL Reagent is demonstrated by its substantial equivalence to the WAKO Chemicals Direct Bilirubin liquid reagent (K970986) which is also based on chemical oxidation. Both test systems are intended to quantitatively measure direct bilirubin in human serum.

In comparison studies against the predicate assay, a correlation coefficient of 0.98476 and a regression equation y = 1.0882 x + 0.1574 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 0.05 mg/dl. The N-ASSAY L D-BIL reagent is linear to 20 mg/dl.

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Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a stylized eagle with its wings spread, enclosed within a circle. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged around the upper portion of the circle.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

1 1698 MAY

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

K981276 Re : N-ASSAY L D-BIL (Direct Bilirubin Assay Reagent) Requlatory Class: II Product Code: CIG Dated: April 2, 1998 Received: April 8, 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 requlations affecting your device can be found in the Code of Federal Regulations, 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 regulation may result in regulatory In addition, FDA may publish further announcements action. 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/dsmamain.html".

Sincerely yours,
Steven Ditman

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

12981276 510(k) Number (if known):

N-ASSAY L D-BIL (Direct Bilirubin Assay Reagent) Device Name:

Indications For Use:

The intended use for the N-ASSAY L D-BIL Reagent is for the quantitative The intended use for the re room in the diagnosis and treatment of various liver diseases. For in vitro diagnostic use only.

(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. 1981276

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Prescription Use (Per 21 CFR 801.109) OR

Over-The-Counter Use _

Optional Format 1-2-96)

3/2/98

Regulation Number and Section

§ 862.1110 Bilirubin (total or direct) test system.

(a)
Identification. A bilirubin (total or direct) test system is a device intended to measure the levels of bilirubin (total or direct) in plasma or serum. Measurements of the levels of bilirubin, an organic compound formed during the normal and abnormal distruction of red blood cells, if used in the diagnosis and treatment of liver, hemolytic hematological, and metabolic disorders, including hepatitis and gall bladder block.(b)
Classification. Class II.