The Roche Diagnostics, Boehringer Mannheim Liquid Direct Bilirubin reagent is intended for use for the quantitative determination of direct 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 destruction 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

Direct bilirubin, in the absence 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 direct bilirubin concentration and can be measured photometrically.

AI/ML Overview

The provided 510(k) summary for the Roche Diagnostics, Boehringer Mannheim Liquid Direct Bilirubin Reagent does not explicitly state acceptance criteria or a detailed study proving the device meets specific performance metrics. Instead, it focuses on demonstrating substantial equivalence to a predicate device.

However, based on the information provided, we can infer the strategy for demonstrating equivalence and what would constitute "acceptance" in this context. The core of the submission is showing that the new device performs similarly to the predicate device, especially for its intended use.

Here's an analysis based on the available text:

1. Table of Acceptance Criteria and Reported Device Performance

The submission implicitly states that the acceptance criterion is "substantial equivalence" to the predicate device, particularly regarding performance characteristics. While no numerical acceptance targets are listed, the document implies that the new device's performance is acceptable if it is comparable to the predicate.

Feature Area	Acceptance Criterion (Implicit)	Reported Device Performance (Implicit)
Intended Use	Same as predicate (quantitative determination of direct bilirubin in serum/plasma of adults/neonates on automated analyzers).	The new device has the same intended use.
Sample Type	Same as predicate (serum or plasma, no preparation).	The new device uses serum or plasma, no preparation.
Analytical Principle	Same as predicate (Diazo reaction with azobilirubin product, measured spectrophotometrically).	The new device uses the same Diazo reaction and spectrophotometric measurement.
Calibration	Similar to predicate (uses commercially available calibrators with assigned values).	The new device uses commercially available calibrators with assigned values for direct bilirubin.
Accuracy / Correlation	Performance "substantially equivalent" to predicate device.	Not explicitly quantified in this summary, but the submission claims substantial equivalence through comparison to the predicate's performance. The original submission (Section V) would likely contain the specific performance data backing this claim.

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

This information is not provided in the given 510(k) summary. The summary refers to "Specific data on the performance of the system have been incorporated into the draft labeling in Section V of this submission." This section would contain details about the actual study: sample sizes (e.g., number of patient samples tested), and likely whether it was retrospective or prospective, and general location of data collection (e.g., in-house lab, clinical sites).

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

This is not applicable in the context of this in vitro diagnostic (IVD) device. For IVD reagents like the direct bilirubin test, the "ground truth" is typically established by comparing results to a recognized reference method or another already validated, legally marketed device (the predicate). There wouldn't be "experts" establishing ground truth in the way a radiologist reads images.

4. Adjudication Method for the Test Set

This is not applicable for this type of IVD device. Adjudication methods (like 2+1, 3+1) are typically used in clinical trials, especially for imaging devices, where human readers consensus is required for ground truth. For an IVD, the comparison is typically against quantitative analytical results.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size (Human Improvement with AI vs. Without AI)

This is not applicable. This submission is for an in vitro diagnostic reagent, not an AI-powered device or an imaging device that involves human readers interpreting results.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done

This is not applicable as it's an IVD reagent, not an AI algorithm. The device itself is the "standalone" entity that produces a quantitative result.

7. The Type of Ground Truth Used

The "ground truth" for this device's performance would be established by:

Comparison to a legally marketed predicate device: The submission explicitly states "substantially equivalent to the currently marketed Roche Diagnostics, Boehringer Mannheim Direct Bilirubin reagent system". Performance studies would involve running patient samples on both the new device and the predicate device and showing acceptable correlation and agreement.
Reference Methods: In some cases, established reference methods for bilirubin measurement might be used, but the primary method for demonstrating equivalence in a 510(k) is usually comparison to the predicate.

8. The Sample Size for the Training Set

This is not applicable in the context of this device. "Training set" refers to data used to train machine learning models. This is a chemical reagent, not an AI algorithm.

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

This is not applicable as there is no "training set" for this type of device.

Summary of the Study (Inferred from the Document):

The study performed to demonstrate substantial equivalence for the Roche Diagnostics, Boehringer Mannheim Liquid Direct Bilirubin Reagent would have involved running a series of patient samples on both the new liquid reagent system and the predicate solid reagent system (Roche Diagnostics, Boehringer Mannheim Direct Bilirubin reagent system, catalog number 704027). The "acceptance criteria" were implicitly that the performance (e.g., accuracy, precision, linearity, interference) of the new reagent was comparable to, or within acceptable limits of variation from, the predicate device.

The specific data details (sample size, statistical analysis, actual performance numbers) are referenced as being in "Section V of this submission" and are not included in the provided 510(k) summary excerpt. The focus of the provided text is on outlining the similarities and minor differences (like reagent stability and preparation) between the new and predicate devices, and asserting that the performance characteristics are substantially equivalent.

Summary

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K981883

JUL 7 1998

ලෙස පොදුන්

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 28, 1998
2) Device name	Proprietary name: Roche Diagnostics, Boehringer Mannheim Liquid DirectBilirubin 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 Direct Bilirubin reagent system, catalog number704027, a modification of the Boehringer Mannheim / Hycel Bilirubin IIreagent system, included in K790335.
4) DeviceDescription	Direct bilirubin, in the absence of a suitable solubilizing agent, is coupled witha 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 thedirect bilirubin concentration and can be measured photometrically.

Continued on next page

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510(k) Summary, Continued

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

The Roche Diagnostics, Boehringer Mannheim Liquid Direct 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 Direct Bilirubin reagent system, catalog number 704027, a modification of the Boehringer Mannheim / Hycel Bilirubin II reagent system, included in K790335.

The following table illustrates the similarities between the Roche Diagnostics, Boehringer Mannheim Liquid Direct 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 DirectBilirubin Reagent	Predicate DirectBilirubin Reagent
Intended Use	Measurement of directbilirubin	Measurement of directbilirubin
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	Uses commerciallyavailable calibratorswith assigned values fordirect bilirubin	Uses commerciallyavailable calibratorswith assigned values fordirect bilirubin

Similarities:

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510(k) Summary, Continued

Feature	New Liquid DirectBilirubin Reagent	Predicate DirectBilirubin Reagent
Calibration Stability	Perform a newcalibration once a week,or with a bottle orreagent lot change	Perform a newcalibration once daily,or with a bottle orreagent lot change
Reagent On-boardStability	4 weeks	14 days
Kit Configuration,Reagent Preparation	R1, liquid, ready-to-useR2, liquid, ready-to-use	R1, liquid, ready to useR2, combine bottles 2(sulfanilic) and 2a(nitrite), then add 2b(diluent)

Comparison to predicate device (continued)

6) Comparison to predicate device, continued

Differences:

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

Performance characteristics:

The performance of the Roche Diagnostics, Boehringer Mannheim Liquid Direct 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 Direct Bilirubin reagent system, catalog number 704027, a modification of the Boehringer Mannheim / Hycel Bilirubin II reagent system, included in K790335.

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Image /page/3/Picture/10 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle-like symbol with three curved lines representing the bird's body and wings. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular fashion around the symbol.

7 1998 JUL

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Luann Ochs Clinical Research Manager Roche Diagnostics, Boehringer Mannheim Corporation 9115 Haque Road Indianapolis, Indiana 46256

Re : K981883 Liquid Direct Bilirubin Reagent Requlatory Class: II Product Code: CIG Dated: May 28, 1998 Received: May 29, 1998

Dear Ms. Ochs:

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, Druq, 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 regulations affecting your device can be found in the Code of Federal Requlations, Title 21, Parts 800 to 895. ಗ್ಗ 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 requlation may result in requlatory 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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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 qeneral 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 "dsmo@fdadr.cdrh.fda.qov".

Sincerely yours,

Steven Autman

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): Device Name: Roche Diagnostics, Boehringer Mannheim Liquid Direct Bilirubin Reagent

Indications for Use:

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use(Per 21 CFR 801.109)	OR	Over-The-Counter Use
		(Optional Format 1-2-96)

Division of Clinical Laboratory Devices

510(k) Number:	K981883
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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.