The Direct Bilirubin assay is used for the quantitation of direct bilirubin in human serum and plasma. Measurement of direct bilirubin, an organic compound formed during the normal and abnormal destruction of red blood cells, is used in the diagnosis and treatment of liver, hemolytic hematological, and metabolic disorders, including hepatitis and gall bladder block.

Device Description

Direct Bilirubin is an in vitro diagnostic assay for the quantitative determination of direct bilirubin in human serum and plasma. Direct (conjugated) bilirubin couples with a diazonium salt in the presence of sulfamic acid to form the colored compound, azobilirubin. The increase in absorbance at 548 nm due to azobilirubin formation is proportional to the direct bilirubin concentration.

AI/ML Overview

Here's an analysis of the provided information regarding the acceptance criteria and study for the Direct Bilirubin assay:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined "acceptance criteria" but rather describes the performance characteristics that demonstrate substantial equivalence to a predicate device. The performance is presented as correlation and precision which are compared to a predicate device.

Performance Metric	Acceptance Criteria (Implied by Predicate Equivalence)	Reported Device Performance (AEROSET System)	Reported Device Performance (ARCHITECT c8000 System)
Correlation Coefficient (r)	High correlation with predicate device	0.995	0.996
Slope	Close to 1 (when comparing to predicate)	1.08	1.08
Y-intercept	Close to 0 (when comparing to predicate)	0.21 mg/dL	0.21 mg/dL
Total %CV (Precision)	Acceptable (e.g., similar to predicate or within clinical limits)	Level 1: 3.6-4.1% Level 2: 0.9-2.6% Level 3: 1.0-2.7% Level 4: 0.7-2.6%	Level 1: 3.0-3.6% Level 2: 0.9-1.2% Level 3: 1.3-1.5% Level 4: 0.8-1.1%
Assay Range	Not explicitly stated as acceptance criteria, but reported	0.1 to 16.9 mg/dL	0.1 to 16.9 mg/dL
Limit of Quantitation (Sensitivity)	Not explicitly stated as acceptance criteria, but reported	0.04 mg/dL	0.04 mg/dL

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

The document states "Comparative performance studies were conducted," but does not specify the sample size for these studies. It also does not mention the country of origin of the data or whether it was retrospective or prospective.

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

This information is not provided in the document. For an in vitro diagnostic assay like this, "ground truth" would typically be established by comparison to a reference method or a legally marketed predicate device, rather than a panel of human experts in the way it might be for image analysis. The document refers to the "Roche Direct Bilirubin assay on the Hitachi® 717 Analyzer" as the predicate device used for comparison.

4. Adjudication Method for the Test Set

This concept is not applicable to this type of in vitro diagnostic device study. Adjudication methods (like 2+1 or 3+1) are typically used in studies involving human readers, for example, to resolve disagreements in image interpretation. Here, the comparison is between the new device and an existing automated assay.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study was not done. This type of study involves multiple human readers evaluating cases and is not relevant for an automated in vitro diagnostic assay that determines a quantitative measurement like bilirubin levels. The study is a comparison of instrument performance.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, this study describes the standalone performance of the Direct Bilirubin assay. It evaluates the device's ability to measure direct bilirubin quantitatively on its own, without direct human interpretation influencing the measurement result itself (though human operators would run the tests). The performance metrics (correlation, slope, y-intercept, precision) are all indicative of the device's inherent analytical capability.

7. The Type of Ground Truth Used

The ground truth for the comparative performance studies was established by comparison to a legally marketed predicate device: the Roche Direct Bilirubin assay on the Hitachi 717 Analyzer. This is a common approach for demonstrating substantial equivalence for in vitro diagnostic devices.

8. The Sample Size for the Training Set

This information is not provided in the document. For in vitro diagnostic assays, the "training set" would typically refer to the data used during the development and calibration of the assay, which is distinct from the validation studies presented for regulatory submission.

9. How the Ground Truth for the Training Set Was Established

This information is not provided in the document. Similar to point 8, the ground truth for an assay's development and calibration would typically involve a combination of reference materials, spiked samples, and comparison to established methods to ensure accuracy and precision across the measuring range.

Summary

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6 2002 SEP

510(k) Summary

Submitter's Name/Address Abbott Laboratories 1920 Hurd Drive Irving, TX 75038

Contact Person Michele Smith-Waheed Senior Regulatory Specialist MS 1-8 Regulatory Affairs (972) 518-7466 Fax (972) 753-3367

Date of Preparation of this Summary:	June 28, 2002
Device Trade or Proprietary Name:	Direct Bilirubin
Device Common/Usual Name or Classification Name:	Direct Bilirubin
Classification Number/Class:	CIG, Class II

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: KO 22180

Test Description:

Section II Page 1

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Substantial Equivalence:

The Direct Bilirubin assay is substantially equivalent to the Roche Direct Bilirubin assay on the Hitachi® 717 Analyzer.

Both assays yield similar Performance Characteristics.

Similarities:

. Both assays are in vitro colorimetric assays.
Both assays can be used for the quantitative determination of direct bilirubin. .
Both assays yield similar clinical results. .
Both assays are based on the reaction of bilirubin with a diazonium salt in the . presence of acid.

Differences:

. Human serum and plasma are suitable specimens for the Direct Bilirubin assay and only human serum is a suitable specimen for Roche Direct Bilirubin assay.
. There is a difference between the assay ranges.
. There is a difference in the use of calibrators.

Intended Use:

The Direct Bilirubin assay is used for the quantitation of direct bilirubin in human serum and plasma.

Section II Page 2

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Performance Characteristics:

Comparative performance studies were conducted using the AEROSET® System and ARCHITECT® c8000™ System. The Direct Bilirubin assay method comparison yielded acceptable correlation with the Roche Direct Bilirubin assay on the Hitachi 717 Analyzer. On the AEROSET System, the correlation coefficient = 0.995, slope = 1.08, and the Y-intercept = 0.21 mg/dL. On the ARCHITECT c8000 System, the correlation coefficient = 0.996, slope = 1.08, and the Y-intercept = 0.21 mg/dL. Precision studies were conducted using the Direct Bilirubin assay. Within-run, between-run, and between-day studies were performed using four levels of control material. On the AEROSET System, the total %CV for Level 1 ranged from 3.6 to 4.1%, Level 2 ranged from 0.9 to 2.6%, Level 3 ranged from 1.0 to 2.7%, and Level 4 ranged from 0.7 to 2.6 %. On the ARCHITECT c8000 System, the total %CV for Level 1 ranged from 3.0 to 3.6%, Level 2 ranged from 0.9 to 1.2%, Level 3 ranged from 1.3 to 1.5%, and Level 4 ranged from 0.8 to 1.1 %. The Direct Bilirubin assay range is 0.1 to 16.9 mg/dL. The limit of quantitation (sensitivity) of the Direct Bilirubin assay is 0.04 mg/dL on the AEROSET System and 0.04 mg/dL on the ARCHITECT c8000 System. These data demonstrate that the performance of the Direct Bilirubin assay is substantially equivalent to the performance of the Roche Direct Bilirubin assay on the Hitachi 717 Analyzer.

Conclusion:

The Direct Bilirubin assay is substantially equivalent to the Roche Direct Bilirubin assay on the Hitachi 717 Analyzer as demonstrated by results obtained in the studies.

Section II Page 3

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DEPARTMENT OF HEALTH & HUMAN SERVICES

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Food and Drug Administration 2098 Gaither Road Rockville MD 20850

6 2002

Ms. Michele Smith-Waheed Senior Regulatory Specialist Abbott Laboratories 1920 Hurd Drive Irving, TX 75038

Re: K022180

Trade/Device Name: Direct bilirubin Regulation Number: 21 CFR 862.1110 Regulation Name: Bilirubin (total and direct) Test System Regulatory Class: Class II Product Code: CIG, JIT Dated: June 28, 2002 Received: July 3, 2002

Dear Ms. Smith-Waheed:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and 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) that do not require approval of a premarket approval application (PMA). 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 (PMA), 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 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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Page 2 -

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" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrb/dsmamain.html".

Sincerely yours,

Steven Butman

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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510(k) Number (if known): KO22-180

Direct Bilirubin 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)

Prescription Use (Per 21 CFR 801.109)

Over-The-Counter Use

(Optional Format 1-2-96)

Veronica P. O'Brien for Di Juan Cooper

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K022180

Direct Bilirubin 510(k) 6/28/2002 Bil D 5 RI doc

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.