The Total Bilirubin assay is used for the quantitation of total bilirubin in human serum and plasma. Measurement of total 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

Total Bilirubin is an in vitro diagnostic assay for the quantitative determination of total bilirubin in human serum and plasma. Total (conjugated and unconjugated) bilirubin couples with the diazo reagent in the presence of a surfactant to form azobilirubin. The increase in absorbance at 548 nm due to azobilirubin formation is directly proportional to the total bilirubin concentration.

AI/ML Overview

Here's an analysis of the provided 510(k) summary regarding the Total Bilirubin assay, structured to address your questions.

1. Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state "acceptance criteria" in a numerical target format (e.g., "correlation coefficient must be >=X"). Instead, it demonstrates substantial equivalence by showing that the new device's performance characteristics are "similar" and "acceptable" when compared to a legally marketed predicate device. The implied acceptance is that the correlation and precision results are sufficiently close to generally accepted standards for a diagnostic assay and comparable to the predicate.

Performance Metric	Acceptance Criteria (Implied)	Reported Device Performance (AEROSET® System)	Reported Device Performance (ARCHITECT® c8000™ System)
Method Comparison/Correlation	High correlation with predicate device (Roche Total Bilirubin)	Correlation coefficient = 0.999	Correlation coefficient = 0.999
Slope	Close to 1.0 (indicating proportional agreement)	Slope = 0.93	Slope = 0.93
Y-intercept	Close to 0.0 (indicating minimal constant bias)	Y-intercept = 0.16 mg/dL	Y-intercept = 0.15 mg/dL
Precision (Total %CV) Level 1	Low %CV, generally acceptable for clinical assays	2.5 to 4.6%	2.2 to 3.4%
Precision (Total %CV) Level 2	Low %CV, generally acceptable for clinical assays	1.0 to 1.9%	1.1 to 1.2%
Precision (Total %CV) Level 3	Low %CV, generally acceptable for clinical assays	0.9 to 1.3%	0.7 to 0.9%
Precision (Total %CV) Level 4	Low %CV, generally acceptable for clinical assays	0.9 to 1.2%	0.6 to 0.9%
Assay Range	Appropriate for clinical use	0.1 to 35.7 mg/dL	0.1 to 35.7 mg/dL
Limit of Quantitation (Sensitivity)	Clinically appropriate low detection	0.03 mg/dL	0.08 mg/dL

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

Sample Size for Test Set: The document does not explicitly state the number of samples used for the comparative performance studies (method comparison). For precision studies, four levels of control material were used, but the number of replicates per level is not specified.
Data Provenance: Not specified. It's common for such studies to use a mix of patient samples and spiked controls to cover the assay range, but the origin (e.g., country, specific populations) and whether they were retrospective or prospective are not mentioned. Given the date of submission (2002), it's highly likely these were retrospective samples or controlled proficiency testing samples.

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

Not applicable. This is an in vitro diagnostic (IVD) assay for a quantitative measurement (total bilirubin). The "ground truth" for method comparison studies in IVDs is typically established by comparing the new device's results to a legally marketed predicate device (the Roche Total Bilirubin assay in this case), often itself validated against a reference method. It does not involve human expert interpretation of images or clinical findings.

4. Adjudication Method for the Test Set:

Not applicable for a quantitative IVD assay. Adjudication methods (like 2+1, 3+1) are common in studies involving subjective interpretation (e.g., radiology, pathology) to reach a consensus ground truth. For this device, the "truth" is the measured concentration.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done:

No, an MRMC study was not done. MRMC studies are used to evaluate the impact of a system (often AI) on human reader performance, typically in diagnostic imaging. This device is a standalone quantitative lab assay.

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

Yes, the performance characteristics described (correlation, precision, assay range, sensitivity) represent the standalone performance of the Total Bilirubin assay itself on the specified automated systems (AEROSET and ARCHITECT c8000), without human interpretation as part of the primary measurement.

7. The Type of Ground Truth Used:

The primary "ground truth" for the comparative performance study was the results obtained from the legally marketed predicate device, the Roche Total Bilirubin assay on the Hitachi 717 Analyzer, combined with established analytical methods for precision and sensitivity. For IVD assays, predicate comparison is a common method for demonstrating substantial equivalence.

8. The Sample Size for the Training Set:

Not applicable. This is a traditional IVD assay, not an AI/ML algorithm that requires a "training set" in the computational sense. The assay is based on a well-established chemical reaction (diazo reagent coupling) rather than a learned model from data.

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

Not applicable. As mentioned, there is no "training set" in the context of an AI/ML algorithm for this type of device. The assay's performance is driven by its chemical formulation and instrument calibration.

Summary

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SEP 1 3 2002

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:	July 15, 2002
Device Trade or Proprietary Name:	Total Bilirubin
Device Common/Usual Name or Classification Name:	Total 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: ko223339

Test Description:

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Substantial Equivalence:

The Total Bilirubin assay is substantially equivalent to the Roche Total Bilirubin assay (K910591) 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 total bilirubin. .
Both assays yield similar clinical results.
Both assays are based on a similar assay principle. .
Human serum and plasma are suitable specimens for both assays. .
. Both assays have similar assay ranges.
. Both assays require a calibration with calibrators.

Differences:

Suitable specimens for the Roche Total Bilirubin assay include neonatal specimens. .

Intended Use:

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

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Performance Characteristics:

Comparative performance studies were conducted using the AEROSET® System and ARCHITECT® c8000™ System. The Total Bilirubin assay method comparison yielded acceptable correlation with the Roche Total Bilirubin assay on the Hitachi 717 Analyzer. On the AEROSET System, the correlation coefficient = 0.999, slope = 0.93, and the Y-intercept = 0.16 mg/dL. On the ARCHITECT c8000 System, the correlation coefficient = 0.999, slope = 0.93, and the Y-intercept = 0.15 mg/dL. Precision studies were conducted using the Total 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 2.5 to 4.6%, Level 2 ranged from 1.0 to 1.9%, Level 3 ranged from 0.9 to 1.3%, and Level 4 ranged from 0.9 to 1.2 %. On the ARCHITECT c8000 System, the total %CV for Level 1 ranged from 2.2 to 3.4%, Level 2 ranged from 1.1 to 1.2%, Level 3 ranged from 0.7 to 0.9%, and Level 4 ranged from 0.6 to 0.9%. The Total Bilirubin assay range is 0.1 to 35.7 mg/dL. The limit of quantitation (sensitivity) of the Total Bilirubin assay is 0.03 mg/dL on the AEROSET System and 0.08 mg/dL on the ARCHITECT c8000 System. These data demonstrate that the performance of the Total Bilirubin assay is substantially equivalent to the performance of the Roche Total Bilirubin assay on the Hitachi 717 Analyzer.

Conclusion:

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

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a stylized caduceus symbol, which is a staff with two snakes coiled around it, and the words "DEPARTMENT OF HEALTH & HUMAN SERVICES" arranged in a circular pattern around the symbol. The logo is black and white.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

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

SFP 1 3 2002

K022339 Re:

Trade/Device Name: Total Bulirubin Regulation Number: 21 CFR 862.1110 Regulation Name: Bilirubin test system Regulatory Class: Class II Product Code: CIG; JIT Dated: July 15, 2002 Received: July 18, 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 requirement; as set forth in the quality systems (QS) 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 1 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/dsma/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): KO22339

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	OR	Over-The-Counter Use
(Per 21 CFR 801.109)

(Optional Format 1-2-96)

tean
(Division Sign-Off)
Division of Clinical Labor
$10(k) Number K022329.

Total Bilirubin 510(k) 7/15/2002 Bil T_5_RI do

000007

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.