The Roche Diagnostics, Boehringer Mannheim Liquid Total Bilirubin reagent is intended for use for the quantitative determination of total bilirubin in serum and plasma of adults and neonates. It is for use on automated clinical chemistry analyzers.

According to the Code of Federal Regulations, Title 21 (Food and Drugs), Part 862.1110, 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.

Device Description

Total bilirubin, in the presence of a suitable solubilizing agent, is coupled with a diazonium ion in a strongly acid medium (ph 1 - 2).

Bilirubin + diazonium ion acid -> Azobilirubin

The intensity of the color of the azobilirubin formed is proportional to the total bilirubin concentration and can be measured photometrically.

AI/ML Overview

The provided document describes a 510(k) premarket notification for the "Roche Diagnostics, Boehringer Mannheim Liquid Total Bilirubin Reagent." This is an in vitro diagnostic device, and the evaluation focuses on demonstrating substantial equivalence to a predicate device rather than presenting a novel AI algorithm. Therefore, many of the typical acceptance criteria and study aspects related to AI/ML devices do not directly apply.

However, I can extract the relevant performance characteristics and details provided for this type of device:

1. Table of Acceptance Criteria and Reported Device Performance

For an in vitro diagnostic such as a reagent, "acceptance criteria" are typically related to analytical performance characteristics like accuracy, precision, linearity, and correlation with a predicate device. The document primarily focuses on demonstrating that the new liquid reagent performs similarly to the predicate device.

Performance Characteristic	Acceptance Criteria (Implied by Substantial Equivalence to Predicate)	Reported Device Performance (New Liquid Total Bilirubin Reagent)
Intended Use	To measure total bilirubin in serum and plasma.	Measurement of total bilirubin in serum and plasma of adults and neonates. For use on automated clinical chemistry analyzers.
Sample Type	Serum or plasma, no preparation required.	Serum or plasma, no preparation required.
Use on Automated Analyzers	Yes	Yes
Test Principle	Diazo reaction with azobilirubin product, measured spectrophotometrically.	Diazo reaction with formation of an azobilirubin product, measured spectrophotometrically. (Bilirubin + diazonium ion (acid) -> Azobilirubin. Intensity of color is proportional to total bilirubin concentration).
Calibration	Two points, blank (saline) and about 2.6 mg/dL total bilirubin.	Two points, blank (saline) and about 2.6 mg/dL total bilirubin.
Calibration Stability	Perform new calibration once a week, or with bottle/reagent lot change.	Perform a new calibration once a week, or with a bottle or reagent lot change.
Reagent On-board Stability	5 days (predicate)	5 weeks (Significant improvement over predicate)
Kit Configuration, Reagent Preparation	R1a, lyophilized, requires reconstitution with buffer; R1, buffer.	R1, liquid, ready-to-use; R2, liquid, ready-to-use. (Significant improvement in ease of use/preparation).
Overall Performance	Substantially equivalent to predicate for similar use.	Stated as "substantially equivalent to other products in commercial distribution intended for similar use," specifically the currently marketed Roche Diagnostics, Boehringer Mannheim Total Bilirubin/DPD reagent system, catalog number 1039034 (K781921). Specific quantitative performance data (e.g., accuracy, precision studies) are not provided in this summary but are referenced as being "incorporated into the draft labeling in Section V of this submission."

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

The 510(k) Summary document does not explicitly state the sample size used for performance testing (e.g., patient samples for method comparison or clinical studies) nor the data provenance (e.g., country of origin, retrospective/prospective). It refers to "Specific data on the performance of the system [that have] been incorporated into the draft labeling in Section V of this submission," which is not included in the provided text.

For this type of IVD, performance data would typically involve:

Method comparison studies: Comparing results from the new device to the predicate device using a range of patient samples.
Precision studies: Assessing within-run, between-run, and total precision.
Linearity studies: Verifying the analytical measurement range.
Interference studies: Testing for substances that might affect results.

Without the "Section V" labeling, these specific details are unavailable.

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

This document describes a diagnostic reagent, not an AI/ML algorithm. Therefore, "ground truth" for the test set is established through analytical methods and comparison to a legally marketed predicate device (and often to reference methods if available), not by human expert opinion or consensus in the context of imaging or clinical interpretation.

4. Adjudication Method for the Test Set

Not applicable in the context of an IVD reagent's analytical performance.

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

Not applicable. This is an IVD reagent, not an AI-assisted diagnostic tool for human readers.

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

This refers to an IVD reagent, which inherently operates "standalone" in the sense that it measures a specific analyte. Its performance is evaluated against analytical standards and predicate devices, not as an "algorithm only" in the AI sense.

7. The Type of Ground Truth Used

For this IVD reagent, the "ground truth" for its performance evaluation would primarily be:

Results from the legally marketed predicate device: The new device's measurements are compared to those obtained from the predicate to demonstrate substantial equivalence.
Reference methods (if applicable and used in internal studies): Highly accurate, often more complex, methods used to determine true analyte concentrations.
Known concentrations in control materials: Used for precision, linearity, and calibration verification.

8. The Sample Size for the Training Set

Not applicable in the context of a chemical reagent and its analytical evaluation. This is not an AI/ML device that uses a "training set."

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

Not applicable, as there is no "training set" for an AI/ML algorithm in this submission.

Summary

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March 14, 2019

Roche Diagnostics/Boehringer Mannheim Gmbh Luann Ochs 9115 Hague Rd. Indianapolis, IN 46256

Re: K981632

Trade/Device Name: Liquid Total Bilirubin Reagent Regulation Number: 21 CFR 862.1110 Regulation Name: Bilirubin (total or direct) test system Regulatory Class: Class II Product Code: CIG, MQM Dated: May 7, 1998 Received: May 8, 1998

Dear Luann Ochs:

This letter corrects our substantially equivalent letter of June 15, 1998.

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 medical devices and radiation-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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510(k) Number (if known): Device Name: Roche Diagnostics, Boehringer Mannheim Liquid Total Bilirubin Reagent

Indications for Use:

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use (Per 21 CFR 801.109)

Over-The-Counter Use

(Optional Format 1-2-96)

(Division Sign-Off)
Division of Clinical Laboratory Zevices
510(k) Number K981633

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K981632

JUN 1 5 1998

510(k) Summary

Introduction	According to the requirements of 21 CFR 807.92, the following informationprovides sufficient detail to understand the basis for a determination ofsubstantial equivalence.
1) Submittername, address,contact	Roche Diagnostics, Boehringer Mannheim Corporation9115 Hague Rd.Indianapolis, IN 46250(317) 845-2000
	Contact Person: Luann Ochs
	Date Prepared: May 7, 1998
2) Device name	Proprietary name: Roche Diagnostics, Boehringer Mannheim Liquid TotalBilirubin Reagent
	Common name: bilirubin (total or direct) test system
	Classification name: Diazo colorimeter, bilirubin, 75CIGDevice Class II
3) Predicatedevice	We claim substantial equivalence to the currently marketed Roche Diagnostics.Boehringer Mannheim Total Bilirubin/DPD reagent system, catalog number1039034, a modification of the Single Vial DPD Total Bilirubin reagentsystem, K781921.
4) DeviceDescription	Total bilirubin, in the presence of a suitable solubilizing agent, is coupled witha diazonium ion in a strongly acid medium (ph 1 - 2).
	Bilirubin + diazonium ionacid-> Azobilirubin
	The intensity of the color of the azobilirubin formed is proportional to the totalbilirubin concentration and can be measured photometrically.

Continued on next page

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510(k) Summary, Continued

The Roche Diagnostics, Boehringer Mannheim Liquid Total Bilirubin reagent 5) Intended use is intended for use for the quantitative determination of total bilirubin in serum and plasma of adults and neonates. It is for use on automated clinical chemistry analyzers.

The Roche Diagnostics, Boehringer Mannheim Liquid Total Bilirubin reagent 6) Comparison is substantially equivalent to other products in commercial distribution to predicate intended for similar use. Most notably it is substantially equivalent to the device currently marketed Roche Diagnostics, Boehringer Mannheim Total Bilirubin/DPD reagent system, catalog number 1039034, a modification of the Single Vial DPD Total Bilirubin reagent system, K781921.

The following table illustrates the similarities between the Roche Diagnostics, Boehringer Mannheim Liquid Total Bilirubin Reagent and the predicate device. Specific data on the performance of the system have been incorporated into the draft labeling in Section V of this submission. Labeling for the predicate device is provided in Section VI.

Feature	New Liquid TotalBilirubin Reagent	Predicate TotalBilirubin Reagent
Intended Use	Measurement of totalbilirubin	Measurement of totalbilirubin
Sample Type	Serum or plasma, nopreparation required	Serum or plasma, nopreparation required
Use on AutomatedChemistry Analyzers?	Yes	Yes
Test Principle	Diazo reaction withformation of anazobilirubin product,measuredspectrophotometrically	Diazo reaction withformation of anazobilirubin product,measuredspectrophotometrically
Calibration	Two points, blank(saline) and about 2.6mg/dL total bilirubin	Two points, blank(saline) and about 2.6mg/dL total bilirubin

Similarities:

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510(k) Summary, Continued

Feature	New Liquid TotalBilirubin Reagent	Predicate TotalBilirubin Reagent
Calibration Stability	Perform a newcalibration once a week,or with a bottle orreagent lot change	Perform a newcalibration once a week,or with a bottle orreagent lot change
Reagent On-boardStability	5 weeks	5 days
Kit Configuration,Reagent Preparation	R1, liquid, ready-to-useR2, liquid, ready-to-use	R1a, lyophilized,requires reconstitutionwith bufferR1, buffer

Comparison to predicate device (continued)

6) Comparison Differences: to predicate device, continued

There are no significant differences between the Roche Diagnostics, Boehringer Mannheim Liquid Total Bilirubin reagent and the predicate device for purposes of considering substantial equivalence.

Performance characteristics:

The performance of the Roche Diagnostics, Boehringer Mannheim Liquid Total Bilirubin reagent is substantially equivalent to other products in commercial distribution intended for similar use. Most notably it is substantially equivalent to the currently marketed Roche Diagnostics, Boehringer Mannheim Total Bilirubin/DPD reagent system, catalog number 1039034, a modification of the Single Vial DPD Total Bilirubin reagent system, K781921.

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.