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

A bilirubin (total and unbound) in the neonate test system is a device intended to measure the levels of bilirubin (total and unbound) in the blood (serum) of newborn infants to aid in indicating the risk of bilirubin encephalopathy (kernicterus).

Device Description

Total Bilirubin is an in vitro diagnostic assay for the quantitative determination of total bilirubin in human serum or plasma of adults and neonates. 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

The provided document is a 510(k) summary for the Abbott Laboratories Total Bilirubin assay. It describes the device, its intended use, and performance characteristics compared to a predicate device.

Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:

1. A table of acceptance criteria and the reported device performance

The document does not explicitly state "acceptance criteria" in a table format. Instead, it describes performance characteristics and considers them "substantially equivalent" if they show strong correlation and acceptable precision compared to a legally marketed predicate device. The implied acceptance criteria are high correlation coefficients (close to 1), acceptable slopes (close to 1), and small Y-intercepts (close to 0) when compared to the predicate.

Performance Metric	Implied Acceptance Criteria (relative to predicate)	Reported Device Performance (AEROSET vs. Hitachi 717)	Reported Device Performance (ARCHITECT c8000 vs. Hitachi 717)	Reported Device Performance (ARCHITECT c8000 vs. AEROSET)
Adult Application (Correlation)
Correlation Coefficient (r)	Close to 1.0	0.9992	0.9992	0.9999
Slope	Close to 1.0	0.96	0.95	0.99
Y-intercept (mg/dL)	Close to 0.0	0.22	0.20	-0.02
Neonate Application (Correlation)
Correlation Coefficient (r)	Close to 1.0	0.9934	0.9921	0.9964
Slope	Close to 1.0	0.96	0.98	1.02
Y-intercept (mg/dL)	Close to 0.0	0.22	0.06	-0.13
Precision (Total %CV)	(Generally low, device-specific)	AEROSET: L1=1.33%, L2=1.56%, L3=1.32%, L4=0.9%	ARCHITECT c8000: L1=1.68%, L2=2.13%, L3=1.84%, L4=1.3%	Not applicable (intra-device precision)
Linearity	Defined range	0.1 to 25 mg/dL	Not specified for predicate, implied match	Not specified for predicate, implied match
Functional Sensitivity (Limit of Quantitation)	Low	< 0.1 mg/dL	Not specified for predicate, implied match	Not specified for predicate, implied match
Limit of Detection (LOD)	Low	0.05 mg/dL	Not specified for predicate, implied match	Not specified for predicate, implied match

2. Sample sizes used for the test set and the data provenance

Adult Application Test Set: 137 serum samples.
Neonate Application Test Set: 52 serum samples.
Data Provenance: The document does not specify the country of origin. The study appears to be retrospective, as it used collected serum samples to compare the new device's performance against an existing, legally marketed predicate device (Roche Total Bilirubin assay on the Hitachi 717 Analyzer).

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

This information is not applicable and therefore not provided in the document. For in vitro diagnostic assays like this, the "ground truth" for the test set is established by the measurements from the predicate device (Roche Total Bilirubin assay on the Hitachi 717 Analyzer), which is assumed to be accurate and reliable. No human experts are involved in establishing the "ground truth" for these types of quantitative measurements.

4. Adjudication method for the test set

This information is not applicable. As explained above, the ground truth is based on quantitative measurements from a predicate device, not on expert interpretations needing adjudication.

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 is not applicable. The device is an in vitro diagnostic assay for measuring total bilirubin levels, not an AI-assisted diagnostic imaging or interpretation tool that involves human readers.

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

This concept is not directly applicable in the context of this device. The "Total Bilirubin" assay is a chemical reaction-based system performed by an automated analyzer (AEROSET System and ARCHITECT c8000 System). Its "performance" inherently represents the "standalone" or "algorithm only" (in the sense of the instrument's automated process) result without human interpretation of the primary measurement itself. The human-in-the-loop aspect would be in clinical decision-making based on the numerical result, not in the measurement process. The study evaluates the performance of this automated system.

7. The type of ground truth used

The ground truth for comparison was the measurements obtained from a legally marketed predicate device: the Roche Total 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

The document does not specify a separate training set. For 510(k) submissions of IVD assays based on substantial equivalence, the focus is typically on validating the performance of the new device against a predicate using clinical samples (the "test set"). There isn't typically a machine learning "training set" in the conventional sense for this type of chemical assay.

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

As no explicit training set is mentioned in the context of machine learning, this question is not applicable. The comparison data rely on the established performance of the predicate device.

Summary

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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA logo on the right. The FDA logo features the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG" in a larger font and "ADMINISTRATION" in a smaller font, both in blue.

March 14, 2019

Abbott Laboratories Linda Morris 1921 Hurd Drive Irving, Texas 75038

Re: K060574

Trade/Device Name: Total Bilirubin Regulation Number: 21 CFR 862.1110 Regulation Name: Bilirubin (total or direct) test system Regulatory Class: Class II Product Code: CIG, MQM, JIT Dated: March 3, 2006 Received: March 6, 2006

Dear Linda Morris:

This letter corrects our substantially equivalent letter of May 3, 2006.

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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to 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

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801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements 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.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Kellie B. Kelm -S

for Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known): K060574

Device Name: Total Bilirubin

Indications For Use:

Prescription Use (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostics Devices (OIVD)

Carol Bencon

Page 1 of _/

5: K060574

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MAY 3 2006

510(k) Summary

Submitter's Name/Address Abbott Laboratories 1921 Hurd Drive Irving, TX 75038

Contact Person Linda Morris Senior Regulatory Specialist MS 2-11 Regulatory Affairs (972) 518-6711 Fax (972) 518-7479

Date of Preparation of this Summary:	March 3, 2006
Device Trade or Proprietary Name:	Total Bilirubin
Device Common/Usual Name orClassification Name:	Total Bilirubin Reagent
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 i

The assigned 510(k) number is: K060574

Test Description:

Total Biltrubin 510(k) March 3, 2006

Section II Page 2 090011

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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. These assays yield substantially equivalent Performance Characteristics.

Similarities:

. Both assays are in vitro colorimetric chemical reactions.
. Both assays can be used for the quantitative analysis of total bilirubin in human serum or plasma of adults and neonates.
. Both assays vield similar results.

Differences:

None

Intended Use:

The Total Bilirubin assay is used for the quantitative analysis of total bilirubin in human serum or plasma of adults and neonates.

Performance Characteristics:

Adult Application: Correlation data are presented in Tables 1 and 3, and Figures 1 through 3. One hundred thirty-seven adult serum samples ranging from 0.21 to 24.41 mg/dL (based on the Roche Total Bilirubin assay on the Hitachi 717 Analyzer assay results) showed a correlation coefficient of 0.9992, slope of 0.96, and Y-intercept of 0.22 mg/dL using the AEROSET System. The ARCHITECT c8000 System showed a correlation coefficient of 0.9992, slope of 0.95, and Y-intercept of 0.20 mg/dL when compared to the Hitachi 717 Analyzer. The ARCHITECT c8000 System showed a correlation coefficient of 0.9999, slope of 0.99 and Y-intercept of -0.02 mg/dL when compared to the AEROSET System. The Total Bilirubin assay method comparison yielded acceptable correlation between the AEROSET System and ARCHITECT c8000 System.

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Total Bilirubin 510(k) March 3, 2006

Section II Page 3 690012

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Neonate Application: Correlation data are presented in Tables 2 and 4, and Figures 4 through 6. Fifty-two neonate serum samples ranging from 4.65 to 15.9 mg/dL (based on the Roche Total Bilirubin assay on the Hitachi 717 Analyzer assay results) showed a correlation coefficient of 0.9934, slope of 0.96, and Y-intercept of 0.22 mg/dL using the AEROSET System. The ARCHITECT c8000 System showed a correlation coefficient of 0.9921, slope of 0.98, and Y-intercept of 0.06 mg/dL when compared to the Hitachi 717 Analyzer. The ARCHITECT c8000 System showed a correlation coefficient of 0.9964, slope of 1.02 and Y-intercept of -0.13 mg/dL when compared to the AEROSET System.

Precision studies were conducted using the Total Bilirubin assay. On the AEROSET System, the total %CV for Level 1 is 1.33%, Level 2 is 1.56%, Level 3 is 1.32%, and Level 4 is 0.9%. On the ARCHITECT c8000 System, the total %CV for Level 1 is 1.68%, Level 2 is 2.13%, Level 3 is 1.84%, and Level 4 is 1.3%. The Total Bilirubin assay is linear from 0.1 to 25 mg/dL. The functional sensitivity (limit of quantitation) of the Total Bilirubin assay is < 0.1 mg/dL and the limit of detection (LOD) 0.05 mg/dL.

These data demonstrate the performance of the Total Bilirubin assay is substantially equivalent to the performance of the Roche Total Bilirubin 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.

Total Bilirubin 510(k) March 3, 2006

Section II

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.