COBAS INTEGRA Bilirubin Direct: The cassette COBAS INTEGRA Bilirubin Direct (BIL-D) contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA systems for the quantitative determination of the direct (conjugated) bilirubin concentration in serum and plasma (test BIL-D, 0-049).

COBAS INTEGRA Total Bilirubin Special: The COBAS INTEGRA Total Bilirubin Special (BILTS) cassette contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA systems for the quantitative determination of total bilirubin in serum and plasma of adults and neonates (test BILTS, 0-985).

Roche Hitachi Total Bilirubin Special: For the quantitative determination of total bilirubin in serum and plasma of adults and neonates on Roche/Hitachi automated clinical chemistry analyzers.

Measurement of the levels of bilirubin and organic compound formed during the normal and abnormal distruction of red cells, if used in the diagnosis of liver, hemolytic hemoatological, and metabolic disorders, including hepatitis and gall bladder block

Device Description

The COBAS INTEGRA and Roche/Hitachi total or direct reagent is intended for use on the COBAS INTEGRA and Roche/Hitachi systems for the quantitative determination of total or direct bilirubin in serum and plasma.

AI/ML Overview

The provided text describes modifications to existing Bilirubin test systems (COBAS INTEGRA Bilirubin Direct, COBAS INTEGRA Total Bilirubin Special, and Roche/Hitachi Total Bilirubin) and seeks substantial equivalence to their predicate devices. The document highlights changes in traceability, quantification of interference, reagent handling, pH values, lower detection limits, and recommended calibrators. It compares the modified devices to the predicate devices, showing similarities in intended use, specimen type, test principle, and some performance characteristics, while noting differences in reagent composition, traceability, and endogenous interferences.

Here's an analysis of the acceptance criteria and the study information, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state "acceptance criteria" but rather presents a comparison of performance characteristics between the predicate and modified devices, implying that the modified device's performance aligns with or improves upon the predicate.

Feature	Predicate Device Performance	Modified Device Performance
COBAS INTEGRA Bilirubin Direct
Lower detection limit	3.1 x 10^-3^ $ΛA$ per mg/dL of direct bilirubin	0.10 mg/dL (Note: The text states a change in stated lower detection limit from 0.81 umol/L to 1.7 umol/L previously, then lists 0.10 mg/dL here. This might be a unit conversion or a specific claim for the modified device based on new methodology rather than a direct comparison to the predicate's stated limit in the same unit.)
Measuring range	0-20 mg/dL	0.10-25 mg/dL
Traceability	Standardized against the manual test performance using the Jendrassic Grof method	Standardized against the Doumas reference method
Endogenous Interferences (Hemolysis)	Even slight hemolysis interferes with the test	No significant interference up to an H index of 10
Endogenous Interferences (Lipemia)	Even slight lipemia interferes with the test	No significant interference up to an L index of 270
Reagent R1 pH	1.1	1.2
COBAS INTEGRA Total Bilirubin Special & Roche/Hitachi Total Bilirubin
Precision (Device 3)	Within run: 0.4% @ 18.53 mg/dL, 2.8% @ 0.91mg/dL Between day: 2.5% @ 18.08 mg/dL, 4.9% @ 0.89 mg/dL	Within run: 0.81% @ 18.81 mg/dL, 3.1% @ 0.87 mg/dL Between day: 0.83% @ 15.41 mg/dL, 2.2% @ 0.86 mg/dL
Measuring range	Device 2: 0-25 mg/dL, 0-250 mg/dL (with post-dilution) Device 3: 0.1-35.0 mg/dL	Device 2: 0-25 mg/dL, 0-100 mg/dL (with post-dilution) Device 3: Same (0.1-35.0 mg/dL)
Endogenous Interferences (Lipemia - Device 2)	No significant interference up to 1800 mg/dL as Intralipid	No significant interference up to 1400 mg/dL as Intralipid

2. Sample size used for the test set and the data provenance:

The document mentions "internal investigation and customer feedback" for the total bilirubin re-evaluation and "communicated to the customers via Reagent Bulletins" regarding shifts in direct bilirubin values. For the stated performance characteristics (e.g., precision, measuring range, interference), it lists numerical values, implying that experiments were conducted. However, the exact sample size used for the test set, or the data provenance (e.g., country of origin, retrospective or prospective nature of the data), is not explicitly stated within the provided text.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g., radiologist with 10 years of experience):

This information is not provided in the document. The context is for in vitro diagnostic reagents, not image-based AI, so clinical expert review in the traditional sense might not apply. Instead, "ground truth" would relate to reference methods or comparative assays as described below.

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set:

This information is not provided in the document. Again, for a chemical assay, this type of adjudication process for a test set is not typically relevant.

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 to the described device. The device is a bilirubin test system (chemical 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 is not applicable to the described device. This device is a chemical assay, not an algorithm, and does not involve human-in-the-loop performance in the context of an AI-driven diagnosis.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

The "ground truth" for the performance characteristics seems to be established through:

Reference Methods:
- For COBAS INTEGRA Bilirubin Direct, traceability was changed to the Doumas reference method. The predicate was standardized against the Jendrassic Grof method.
- For COBAS INTEGRA Total Bilirubin Special and Roche/Hitachi Total Bilirubin, they are standardized against the Doumas reference method.
Comparative Assays: Performance characteristics like precision, measuring range, and interference levels are determined by running the assay and comparing the results against established analytical methods and specifications.
Internal Investigation and Re-evaluation: As stated for the Total Bilirubin, "Roche Diagnostics has re-evaluated the assignments for the Total Bilirubin assays and has adjusted the C.f.a.s calibrator setpoints for both methods... The results were verified by using US reference laboratory."

8. The sample size for the training set:

This information is not provided. As these are chemical reagents and not machine learning models in the usual sense, the concept of a "training set" with specific sample sizes for algorithm development is not directly applicable. The development and optimization of the reagents involve analytical studies and calibrations, not 'training' on a dataset in the AI context.

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

This information is not provided and is largely not applicable in the context of chemical reagent development as described. The "ground truth" for calibration and validation of the reagent system centers around established reference methods (like the Doumas method) and analytical performance testing, rather than a "training set" with independently established ground truth as would be used for AI/ML models. For the calibrators, "Roche Diagnostics has re-evaluated the assignments... and has adjusted the C.f.a.s calibrator setpoints for both methods... The results were verified by using US reference laboratory." This suggests reference laboratory analysis for calibrator value assignment.

Summary

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510(k) Summary

K063543

Roche Diagnostics Corporation hereby submits this Bundled Special 510(k): Introduction Device Modification to provide notification of modifications to our Bilirubin (Total and Direct) test systems. The reagents were originally cleared for use as:

COBAS INTEGRA Bilirubin Direct K951595 COBAS INTEGRA Total Bilirubin Special K981632/A001 Roche/Hitachi Total Bilirubin K981632/A001

Note that COBAS INTEGRA Total Bilirubin Special and Roche/Hitachi Total Bilirubin are different applications of the exact same reagent.

Modifications to the test systems include:

Device 1: COBAS INTEGRA Bilirubin Direct

Changes to the traceability .
In the Limitations section, quantification of lipemia and hemolysis . interference, rather than a statement to avoid lipemia and hemolyzed specimens
Clarification for reagent handling .
Change to pH value for R1 from 1.1 to 1.2 .
Change in stated lower detection limit from 0.81 umol/L to 1.7 . umol/L. The change is due to Roche's decision to redefine the lower detection limit for clinical chemistry test systems to match the lower end of the measuring range even if data support a lower detection limit. This does not represent a change in actual performance; but rather only a change in the stated performance claim.
Change in recommended calibrator to the Calibrator for Automated . systems (C.f.a.s.) cleared by FDA under 510(k) K062319
Other editorial labeling changes .

Device 2: COBAS INTEGRA Total Bilirubin Special K981632/A001

. Modifications to specimen collection
Labeling changes addition of two clarifying statements in the . Specimen collection and preparation section: "Do not use cordblood samples" and "Underfilled lithium heparin sample tubes may cause elevated results"
Other editorial labeling changes .

Continued on next page

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510(k) Summary – Calibrator for Automated Systems

(C.f.a.s), Continued

Introduction(continued)	Device 3: Roche/Hitachi Total Bilirubin K981632/A001
	Modifications to specimen collection section to includeclarification that underfilled lithium heparin sample tubes maycause elevated results Clarification for reagent handling Labeling changes – Addition of two clarifying statements inthe Specimen collection and preparation section: “Do not usecordblood samples” and “Underfilled lithium heparin sampletubes may cause elevated results” Other editorial labeling changes
Submittername, address,contact	Roche Diagnostics9115 Hague RdIndianapolis IN 46250(317) 521-3723Contact person: Corina HarperDate prepared: October 30, 2006
Device Name	Device 1:Proprietary name: COBAS INTEGRA Bilirubin DirectCommon name: Bilirubin DirectClassification name: Bilirubin (total or direct) test systemDevice 2:Proprietary name: COBAS INTEGRA Total Bilirubin SpecialCommon name: Total BilirubinClassification name: Bilirubin (total or direct) test systemDevice 3:Proprietary name: Roche/Hitachi Total BilirubinCommon name: Total BilirubinClassification name: Bilirubin (total or direct) test system

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The establishment registration number for Roche Diagnostics Gmbh Penzberg Establishment registration is 9610529.

The establishment registration number for Roche Diagnostics Corporation Indianapolis is 1823260.

Classification	The FDA has classified Bilirubin (total or direct) test system in Class II.
	Panel	ClassificationNumber	Classification Name	RegulationCitation
	75 ClinicalChemistry	CIG	Bilirubin (total or direct)test system	21 CFR 862.1110
DeviceDescription	The COBAS INTEGRA and Roche/Hitachi total or direct reagent is intendedfor use on the COBAS INTEGRA and Roche/Hitachi systems for thequantitative determination of total or direct bilirubin in serum and plasma.
Intended use	Device 1: COBAS INTEGRA Bilirubin Direct:The cassette COBAS INTERGA Bilirubin Direct contains an in vitrodiagnostic reagent system intended for use on COBAS INTEGRA systems forthe quantitative determination of the direct (conjugated) bilirubinconcentration in serum and plasma..Device 2: COBAS INTEGRA Total Bilirubin Special:The COBAS INTERGA Total Bilirubin Special cassette contains an in vitrodiagnostic reagent system intended for use on COBAS INTEGRA systems forthe quantitative determination of total bilirubin in serum and plasma of adultsand neonates.Device 3: Roche/Hitachi Total Bilirubin:For the quantitative determination of total bilirubin in serum and plasma ofadults and neonates on Roche/Hitachi automated clinical chemistry analyzers.
PredicateDevice	We claim substantial equivalence toDevice 1: Bilirubin Direct cleared as K951595Device 2: Total Bilirubin cleared as K981632/A001Device 3: Total Bilirubin cleared as K981632/A001

Continued on next page

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510(k) Summary – Calibrator for Automated Systems

(C.f.a.s), Continued

The table below indicates the similarities and differences between the Substantial equivalency modified Bilirubin direct or total reagents and their predicate devices. Similarities

Feature	Predicate device:	Modified device:
	Device 1: COBAS INTEGRABilirubin Direct K951595	COBAS INTEGRA Bilirubin Direct
	Device 2: COBAS INTEGRA TotalBilirubin Special K981632/A001	COBAS INTEGRA Total Bilirubin Special
	Device 3: Roche/Hitachi TotalBilirubin K981632/A001	Roche/Hitachi Total Bilirubin
General
Intended Use/Indications forUse	Device 1: COBAS INTEGRA Bilirubin DirectThe cassette COBAS INTEGRA Bilirubin Direct(BIL-D) contains an in vitro diagnostic reagentsystem intended for use on COBAS INTEGRAsystems for the quantitative determination of thedirect (conjugated) bilirubin concentration inserum and plasma (test BIL-D, 0-049).	Same
	Device 3: COBAS INTEGRA Total Bilirubin SpecialThe COBAS INTEGRA Total Bilirubin Special(BILTS) cassette contains an in vitro diagnosticreagent system intended for use on COBASINTEGRA systems for the quantitativedetermination of total bilirubin in serum andplasma of adults and neonates (test BILTS, 0-985).	Same
	Roche Hitachi Total Bilirubin SpecialFor the quantitative determination of total bilirubinin serum and plasma of adults and neonates onRoche/Hitachi automated clinical chemistryanalyzers.	Same
Specimen	Device 1: serum and plasma	Same
	Device 2: serum and plasma of adults andneonates	Same
	Device 3: serum and plasma of adults andneonates	Same
Test Principle
Referencemethod	Device 1: Diazo method	Same
	Device 2: Diazo method	Same
	Device 3: Diazo method	Same
Reagent information
Reagentcomposition	Device 2: COBAS INTEGRA TotalBilirubin SpecialR1: Sodium acetate buffer 85mmol/L, Sulfamic acid 110 mmol/LR2: Hydrochloric acid 100 mmol/L,Diazonium ion 3 mmol/L	Same
	Device 3: Roche/Hitachi TotalBilirubinR1: Sodium acetate buffer 85mmol/L, Sulfamic acid 110 mmol/LR2: Hydrochloric acid 100 mmol/L,Diazonium ion 3 mmol/L	Same
Stability - shelflife and on-board	Device 1:15-25 °C until expiration dateOn-board at 8 °C 12 weeks	15-25 °C until expiration dateCOBAS INTEGRA 400/400 plus:On-board at 10-15 °C 8 weeksCOBAS INTEGRA 700/800:On-board at 8 °C 12 weeks
	Device 2:2-8 °C until expiration dateCOBAS INTEGRA 700On-board at 8 °C 5 weeks	2-8 °C until expiration dateCOBAS INTEGRA 400/400 plus:On-board at 10-15 °C 5 weeksCOBAS INTEGRA 700/800:On-board at 8 °C 5 weeks
	Device 3:2-8 °C until expiration date35 days opened and refrigerated on theanalyzer	Same

Calibrator	Device1:Calibrator (human)	Calibrator f.a.s.
	Device 2:Calibrator f.a.s.	Same
	Device 3:Calibrator f.a.s.	Same
Quality control	Device1:Control Serum NControl Serum P	Precinorm U, Precipath UPrecinorm U plus, Precipath U plus,
	Device 2:Precinorm U, Precipath UPrecinorm U plus, Precipath U plus	Same
	Device 3:Precinorm U, Precipath UPrecitrol N, Precitrol A,	Precinorm U, Precipath UPrecinorm U plus, Precipath U plus
Traceability	Device 2:Standardized against the Doumasreference method	Same
	Device 3:Standardized against the Doumasreference method	Same
Performance characteristics

Precision	Device1:Within run:1.7% @ 6.1 µmol/L0.53% @ 20.1 µmol/LBetween day:1.1% @ 6.1 µmol/L1.1% @ 20.1 µmol/LTotal:1.9% @ 6.1 µmol/L1.2% @ 20.1 µmol/L	SameWithin run and total CV% reported
	Device 2:Within run:2.44% @ 15.80 µmol/L1.39% @ 54.00 µmol/LBetween day:4.13% @ 14.7 µmol/L2.15% @ 47.20 µmol/L	Same
	Device 3:Within run:0.4% @ 18.53 mg/dL2.8% @ 0.91mg/dLBetween day:2.5% @ 18.08 mg/dL4.9% @ 0.89 mg/dL	Within run:0.81% @ 18.81 mg/dL3.1% @ 0.87 mg/dLBetween day:0.83% @ 15.41 mg/dL2.2% @ 0.86 mg/dL
Measuringrange	Device1:0-20 mg/dL	0.10-25 mg/dL
	Device 2:0-25 mg/dL0-250 mg/dL (with postdulion)	0-25 mg/dL0-100 mg/dL (with postdulion)
	Device 3:0.1-35.0 mg/dL	Same
Lower	Device1:

detection limit	3.1 x 10-3 $ΛA$ per mg/dL of direct	0.10 mg/dL
	bilirubin

	Device 2:
	0.063 mg/dL	Same

	Device 3:
	0.1 mg/dL	Same

Expected	Device1:
values	Serum 0-0.2 mg/dL	Same
(literature
reference)
	Device 2 and 3:	Same for Device 2 and 3
	Adults and children: up to 1.0
	mg/dL

	Neonates:

	Age of newborn Premature
	24hrs: 1.0-6.0 mg/dL
	48hrs: 6.0-8.0 mg/dL
	3-5 days: 10.0-15.0 mg/dL

	Age of newborn Full Term
	24hrs: 2.0-6.0 mg/dL
	48hrs: 6.0-7.0 mg/dL
	3-5 days: 4.0-12.0 mg/dL

Endogenous	Device 3:
interferences	Serum and Plasma:	Same
	Hemolysis: no significant
	interferences up to an H index of
	1000
	Lipemia:
	significant negative	N/A - assay not offered on this
	interferences at an L index	instruments

	greater than 600 (on Hitachi
	704,717,914,736,737,747)
	No significant interference up	Same
	to an L index of 1000 (on
	Hitachi 902,911, 912, 917)

Exogenous	Device 2:	Same
interferences	Ascorbic acid at 30 mg/dL causes
	artificially decreased total bilirubin
	values

	Device 3:	Same
	Indican: no significant interferences
	up to levels of 10 mg/dL

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510(k) Summary – Calibrator for Automated Systems

(C.f.a.s), Continued

Substantial	The table below indicates the differences between the modified Bilirubin
Differences	direct or total reagents and their predicate devices.

Feature	Predicate device:COBAS INTEGRA Bilirubin DirectK951595	Modified device:COBAS INTEGRA Bilirubin Direct
	COBAS INTEGRA Total BilirubinSpecial K981632/A001	COBAS INTEGRA Total BilirubinSpecial
	Roche/Hitachi Total BilirubinK981632/A001	Roche/Hitachi Total Bilirubin
Reagent information
Reagentcomposition	Device 1: COBAS INTEGRABilirubin DirectR1: Sulfanic acid 35 mmol/L, Oxalicacid 40 mmol/L, HEDTA 4.0mmol/L, pH 1.1	R1: Sulfanic acid 35 mmol/L, Oxalicacid 40 mmol/L, HEDTA 4.0mmol/L, pH 1.2
	R2: Sodium nitrite 3.9 mmol/L, pH6.0	Same
Traceability	Device 1:Standardized against the manual testperformance using the JendrassicGrof method	Standardized against the Doumasreference method
Endogenousinterferences	Device1:Hemolysis: even slight hemolysisinterferes with the testLipemia: : even slight lipemiainterferes with the test	Hemolysis: No significantinterference up to an H index of 10Lipemia: No significant interferenceup to an L index of 270
	Device 2:Hemolysis: No significantinterference up to 1000 mg/dLLipemia: No significant interferenceup to 1800 mg/dL as Intralipid	Hemolysis: No significantinterference up to 1000 mg/dLLipemia: No significant interferenceup to 1400 mg/dL as Intralipid

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Additionalinformation formodifications tovaluesassignmentprocess andtraceability	Direct Bilirubin:Roche Diagnostics has revised the calibration of the COBASINTEGRA Bilirubin Direct method due to ongoing quality assuranceand customer feedback. Traceability was changed to the Doumasmethod, and the concurrent change in Quality Control limits for thismethod were intended to minimize or eliminate any discrepancies seenby the users. The impact of using new setpoints was shift to directbilirubin values lower when compared to the values obtained usingprevious setpoints. The shift occurred in both controls and patientspecimens.The revised setpoints or revised values for controls and its clinicalsignificance were communicated to the customers via ReagentBulletins in April 2002, March 2004, November 2004.Another communication regarding low recovery ofPrecinom U/Precinorm U Plus controls was communicated in May2006.
	Total Bilirubin:Roche Diagnostics has re-evaluated the assignments for the TotalBilirubin assays and has adjusted the C.f.a.s calibrator setpoints forboth methods available on the COBAS INTEGRA and Roche/Hitachianalyzers. This change was triggered by internal investigation andcustomer feedback. The Roche Diagnostics US Standardizationlaboratory has reassigned the values based on a new procedure whichmaintained the same traceability to the Doumas method. The resultswere verified by using US reference laboratory.The revised setpoints or revised values for controls werecommunicated to the customers via a Reagent Bulletins in August2006.
ProposedLabeling	Proposed labeling sufficient to describe the device, its intended use, and thedirections for use can be found in Section V. We believe the proposed versionof the device labeling presented contains all of the technical informationrequired per 21 CFR 809.10.
Validation andDesign Control	Development activities were conducted under appropriate design controlprocedures and the overall product specifications were met. The Declarationof Conformity with Design Controls and Results of Risk Analysis areprovided in Section 5.1. Analytical Performance.
Confidentiality	Roche Diagnostics Corporation requests that the FDA not disclose the natureor existence of this submission until the substantial equivalence decision hasbeen reached.

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Modification of the Bilirubin Direct and Total reagents does not affect the Closing intended use or indications for use of the device as described in the labeling, nor does it alter the fundamental scientific technology of the device. Therefore, we trust the information provided in this Special 510(k) will support a decision of substantial equivalence of the Bilirubin Direct and Total to their predicate.

If you have any questions or require further information, please do not hesitate to contact this office.

Phone: (317) 521-3831
· FAX: (317) 521-2324
email: corina.harper@roche.com

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/11/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo features a stylized eagle with its wings spread, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the eagle. The logo is black and white.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Corina Harper, Regulatory Affairs Consultant Roche Diagnostics Corporation 9115 Hague Road Indianapolis, IN 46250

DEC 2 2 2006

Re: K063543

Trade/Device Name: COBAS Integra Bilirubin Direct COBAS Integra Total Bilirubin Special Roche/Hitachi Bilirubin Total Regulation Number: 21 CFR 862.1110 Regulation Name: Bilirubin (total or direct) test system Regulatory Class: Class II Product Code: CIG Dated: November 22, 2006 Received: November 24, 2006

Dear Ms. Harper:

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 Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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 Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2 -

This letter will allow you to begin marketing your device as described in your Section 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 information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0490. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97), You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (240) 276-3150 or at its Internet address at http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Jean M. Cooper, M.S., D.V.M.

Sean M. Cooper, M.S., D.V.M. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known): K063543

Device Name:

COBAS INTEGRA Bilirubin Direct COBAS INTEGRA Total Bilirubin Special Roche/Hitachi Total Bilirubin

Indications For Use: COBAS INTEGRA Bilirubin Direct

The cassette COBAS INTEGRA Bilirubin Direct (BIL-D) contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA systems for the quantitative determination of the direct (conjugated) bilirubin concentration in serum and plasma (test BIL-D, 0-049).

COBAS INTEGRA Total Bilirubin Special

The COBAS INTEGRA Total Bilirubin Special (BILTS) cassette contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA systems for the quantitative determination of total bilirubin in serum and plasma of adults and neonates (test BILTS, 0-985).

Roche Hitachi Total Bilirubin Special

For the quantitative determination of total bilirubin in serum and plasma of adults and neonates on Roche/Hitachi automated clinical chemistry analyzers.

Prescription Use XXX (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)

Concurrenge of ODRH, Office of In Vitro Diagnostic Devices (OIVD) Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

Page 1 of 1

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.