COBAS INTEGRA BILIRUBIN DIRECT GEN.2

K123965 · Roche Diagnostics · CIG · Feb 28, 2013 · Clinical Chemistry

Device Facts

• Record ID: K123965
• Device Name: COBAS INTEGRA BILIRUBIN DIRECT GEN.2
• Applicant: Roche Diagnostics
• Product Code: CIG · Clinical Chemistry
• Decision Date: Feb 28, 2013
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1110
• Device Class: Class 2

Intended Use

COBAS INTEGRA Bilirubin Direct Gen.2 is an in vitro test for the quantitative determination of direct bilirubin in human serum and plasma on COBAS INTEGRA systems. Measurement of the levels of 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 Story

In vitro diagnostic reagent kit for quantitative measurement of direct bilirubin in human serum and plasma. Operates on COBAS INTEGRA clinical chemistry analyzers. Principle: diazo colorimetric method; conjugated and delta-bilirubin react with 3,5-dichlorophenyl diazonium salt in acid buffer to form red-colored azobilirubin. Color intensity measured photometrically; proportional to direct bilirubin concentration. Used in clinical laboratories by trained personnel. Output provides bilirubin concentration levels to assist physicians in diagnosing and monitoring liver, hemolytic, hematological, and metabolic disorders.

Clinical Evidence

Bench testing only. Precision evaluated per CLSI EP5-A2 (n=21 days, human sera/controls). Linearity assessed per CLSI EP6-A. LoB/LoD/LoQ determined per CLSI EP17-A2 (LoB 0.05 mg/dL, LoD 0.07 mg/dL, LoQ 0.07 mg/dL). Analytical specificity tested against endogenous substances (hemoglobin, lipids) and 18 common drugs. Method comparison (n=71) against predicate yielded y = 1.0490x + 0.0699 (r2=0.9979). Matrix comparison confirmed suitability of Li-heparin, K2-EDTA, and K3-EDTA.

Technological Characteristics

Quantitative diazo colorimetric assay. Reagent 1: Phosphoric acid (85 mmol/L), HEDTA (4.0 mmol/L), NaCl (50 mmol/L), detergent, pH 1.9. Reagent 2: 3,5-Dichlorophenyl diazonium (1.5 mmol/L), pH 1.3. Photometric measurement on COBAS INTEGRA clinical chemistry analyzer. Standardized against Doumas manual reference method. Measuring range 0.07–13.8 mg/dL.

Indications for Use

Indicated for quantitative determination of direct bilirubin in human serum and plasma on COBAS INTEGRA systems to aid in diagnosis and treatment of liver, hemolytic, hematological, and metabolic disorders (e.g., hepatitis, gall bladder block).

Regulatory Classification

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.

Predicate Devices

• COBAS INTEGRA Bilirubin Direct reagent (k063543)

Submission Summary (Full Text)

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# 510(k) Summary for COBAS INTEGRA Bilirubin Direct Gen.2

| 510(k) number | k123965 | | | | | | | | |
|------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------|-------------------------|------------|-------|-----|----------|-----------------------------------------------------------|-------------------------|
| Purpose of submission | Roche Diagnostics hereby submits this 510(k) to provide FDA with notification of intent to market a new device named COBAS INTEGRA Bilirubin Direct Gen.2 reagent.<br>This candidate device is a new reagent that was developed by Roche Diagnostics. The previous generation of reagent, COBAS INTEGRA Bilirubin Direct, was cleared in 510(k) k063543 and serves as the predicate device. The candidate and predicate devices use the same calibrator and controls. Only the reagents differ. This submission presents data to support clearance of this new reagent. | | | | | | | | |
| Measurand | Direct Bilirubin | | | | | | | | |
| Type of test | Quantitative diazo colorimetric method | | | | | | | | |
| Applicant | Roche Diagnostics | | | | | | | | |
| Candidate device names | Proprietary name:<br>COBAS INTEGRA Bilirubin Direct Gen.2<br>Common name:<br>Bilirubin Direct Gen.2 | | | | | | | | |
| Regulatory information | <table><tr><th>Product Code</th><th>Classification</th><th>Regulation</th><th>Panel</th></tr><tr><td>CIG</td><td>Class II</td><td>21 CFR 862.1110 (Bilirubin (total or direct) test system)</td><td>Clinical Chemistry (75)</td></tr></table> | Product Code | Classification | Regulation | Panel | CIG | Class II | 21 CFR 862.1110 (Bilirubin (total or direct) test system) | Clinical Chemistry (75) |
| Product Code | Classification | Regulation | Panel | | | | | | |
| CIG | Class II | 21 CFR 862.1110 (Bilirubin (total or direct) test system) | Clinical Chemistry (75) | | | | | | |

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| Intended use | In vitro test for the quantitative determination of direct bilirubin in human<br>serum and plasma on COBAS INTEGRA systems. |
|---------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Indications for<br>use | COBAS INTEGRA Bilirubin Direct Gen.2 is an in vitro test for the<br>quantitative determination of direct bilirubin in human serum and plasma on<br>COBAS INTEGRA systems. Measurement of the levels of bilirubin, an<br>organic compound formed during the normal and abnormal destruction of red<br>blood cells, is used in the diagnosis and treatment of liver, hemolytic,<br>hematological, and metabolic disorders, including hepatitis and gall bladder<br>block. |
| Special<br>conditions for<br>use | For prescription use only |
| Special<br>instrument<br>requirements | For use on the COBAS INTEGRA clinical chemistry analyzer |
| Candidate<br>device<br>description | COBAS INTEGRA Bilirubin Direct Gen.2 reagent provides quantitative<br>measurement of the direct bilirubin that is present in a human serum or<br>human plasma sample.<br><br>Reagents are packaged in a cassette with two bottles labeled with their<br>instrument positioning, R1 and SR. R1, or Reagent 1, contains Phosphoric<br>acid 85 mmol/L, NaCl 50 mmol/L, and HEDTA 4.0 mmol/L at pH 1.9. SR,<br>or Start Reagent, is a 3,5-dichlorophenyl diazonium salt at 1.5 mmol/L in acid<br>buffer, pH 1.3. |
| Predicate<br>device | Roche Diagnostics claims substantial equivalence to the COBAS INTEGRA<br>Bilirubin Direct reagent that was cleared with the Special 510(k) k063543. |
| | Continued on next page |

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The following table compares the identical features of the candidate device to Substantial equivalence the predicate device that was cleared in 510(k) k063543. similarities

| Feature | Predicate Device:<br>Bilirubin Direct | Candidate Device:<br>Bilirubin Direct Gen.2 |
|-----------------------|----------------------------------------------------------------------------------------------|---------------------------------------------|
| Sample Types | Serum and plasma | Same |
| Reference Method | Diazo colorimetric method | Same |
| Calibrator | Calibrator for automated systems<br>(C.f.a.s.) and deionized water as the<br>zero calibrator | Same |
| Calibration Stability | Recalibrate with each lot as and<br>required following quality control<br>procedures | Same |
| Calibration Mode | Linear regression | Same |
| Traceability | Standardized against the Doumas<br>manual reference method | Same |

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The following table compares the different features of the candidate device to Substantial the predicate device that was cleared in 510(k) k063543. equivalence differences .

| Feature | Predicate Device:<br>Bilirubin Direct | Candidate Device:<br>Bilirubin Direct Gen.2 |
|---------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | COBAS INTEGRA Bilirubin<br>Direct (BIL-D) contains an in<br>vitro diagnostic reagent system<br>intended for use on COBAS<br>INTEGRA systems for the<br>quantitative determination of the<br>direct (conjugated) bilirubin<br>concentration in serum and<br>plasma. | In vitro test for the quantitative<br>determination of direct bilirubin in<br>human serum and plasma on<br>COBAS INTEGRA systems. |
| Indications for Use | The cassette COBAS INTEGRA<br>Bilirubin Direct (BIL-D) contains<br>an in vitro diagnostic reagent<br>system intended for use on<br>COBAS INTEGRA systems for<br>the quantitative determination of<br>the direct (conjugated) bilirubin<br>concentration in serum and<br>plasma (test BIL-D, 0-049).<br>Measurement of the levels of<br>bilirubin, an organic compound<br>formed during the normal and<br>abnormal destruction of red blood<br>cells, is used in the diagnosis of<br>liver, hemolytic, hematological,<br>and metabolic disorders, including<br>hepatitis and gall bladder block. | COBAS INTEGRA Bilirubin<br>Direct Gen.2 is an in vitro test for<br>the quantitative determination of<br>direct bilirubin in human serum<br>and plasma on COBAS INTEGRA<br>systems.<br>Measurement of the levels of 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. |
| | Permissible<br>Anticoagulants | Li-heparin |
| Instrument Platform | COBAS INTEGRA 400,<br>400 Plus, 700, and 800 | COBAS INTEGRA 800 |

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## Substantial equivalence - differences continued

| Feature | Predicate Device:<br>Bilirubin Direct | Candidate Device:<br>Bilirubin Direct Gen.2 |
|---------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Reagent Composition | R1:<br>Sulfanilic acid 35 mmol/L,<br>Oxalic acid 40 mmol/L,<br>HEDTA 4.0 mmol/L, and<br>pH 1.2<br><br>R2:<br>Sodium nitrite 3.9 mmol/L and<br>pH 6.0<br><br>Sulfanilic acid reacts with sodium<br>nitrite to form diazotized<br>sulfanilic acid. | R1:<br>Phosphoric acid 85 mmol/L,<br>NaCl 50 mmol/L,<br>HEDTA 4.0 mmol/L, and<br>pH 1.9<br><br>SR:<br>3,5-DPD 1.5 mmol/L and<br>pH 1.3 |
| Reagent Shelf Life<br>Stability | 15-25 °C until expiration date | 2-8 °C until expiration date |
| Reagent On-Board<br>Stability | COBAS INTEGRA 700/800:<br>8 °C for 12 weeks<br><br>COBAS INTEGRA 400/400 plus:<br>10-15 °C for 8 weeks | COBAS INTEGRA 800:<br>8 °C for 6 weeks |
| Controls | Precinorm U plus,<br>Precipath U plus,<br>Precinorm U,<br>Precipath U | Precinorm U plus,<br>Precipath U plus,<br>PreciControl ClinChem Multi 1A,<br>PreciControl ClinChem Multi 2A<br><br>AThese two new controls were<br>cleared for use with bilirubin<br>direct with 510(k) # k102016. |
| Measuring Range | 0.10 – 25 mg/dL | 0.07 – 13.8 mg/dL |
| Expected Values | 0 to 0.2 mg/dL | ≤ 0.20 mg/dL |
| Lower Limits of<br>Measure | LDL = 0.10 mg/dL | LoB = 0.05 mg/dL<br>LoD = 0.07 mg/dL<br>LoQ = 0.07 mg/dL |

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| Test principle | COBAS INTEGRA Bilirubin Direct Gen.2 measures direct bilirubin by<br>employing the diazo colorimetric method. Conjugated bilirubin and δ-bilirubin (direct bilirubin) react directly with 3,5-dichlorophenyl diazonium<br>salt in acid buffer to form the red-colored azobilirubin. The color intensity of<br>the red azobilirubin formed is directly proportional to the direct bilirubin<br>concentration. The color intensity is measured photometrically by a COBAS<br>INTEGRA clinical chemistry analyzer. |
|-------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Precision/<br>reproducibility | Precision was determined according to CLSI EP5-A2. The study included<br>human sera samples (0.12, 3.76, and 13.2 mg/dL) and two serum-based<br>control samples in two aliquots per run and two runs per day for 21 days.<br><br>Here are summaries of the repeatability and intermediate precision data. |
| Repeatability Summary | |

| Specimen | PNU | PPU | Human Serum 1 | Human Serum 2 | Human Serum 3 |
|--------------------------------------|------|------|---------------|---------------|---------------|
| Total Mean (mg/dL) | 0.75 | 1.9 | 0.12 | 3.8 | 13.2 |
| Within Run Imprecision<br>SD (mg/dL) | 0.01 | 0.01 | 0.01 | 0.01 | 0.04 |
| Within Run Imprecision<br>CV% | 1.2 | 0.6 | 7.4 | 0.4 | 0.3 |
| Min (mg/dL) | 0.72 | 1.9 | 0.09 | 3.7 | 13.1 |
| Max (mg/dL) | 0.78 | 2.0 | 0.13 | 3.8 | 13.3 |

## Intermediate Precision

| Specimen | PNU | PPU | Human Serum 1 | Human Serum 2 | Human Serum 3 |
|---------------------------------|------|------|---------------|---------------|---------------|
| Total Mean (mg/dL) | 0.75 | 1.9 | 0.12 | 3.8 | 13.2 |
| Total Imprecision<br>SD (mg/dL) | 0.01 | 0.02 | 0.01 | 0.04 | 0.05 |
| Total Imprecision<br>CV% | 1.6 | 1.0 | 7.7 | 1.0 | 0.4 |
| Min (mg/dL) | 0.72 | 1.9 | 0.09 | 3.7 | 13.1 |
| Max (mg/dL) | 0.78 | 2.0 | 0.13 | 3.8 | 13.3 |

Values that appear in bold type also appear in the labeling.

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Linearity/ assay reportable range

Linearity was assessed according to CLSI EP6-A with one batch of reagent, in one run, and with samples measured in triplicate. Two separate dilution series differing by sample type (serum and plasma) were prepared with thirteen levels each. Lithium-heparin was used to prepare the plasma sample series. The highest concentration samples exceed the desired measuring range. The highest concentration samples were created by taking low analyte native samples and spiking them with ditaurobilirubin.

Measuring Ranges that are Supported by the Linearity Data

| | Plasma | Serum |
|-------------------------------------|-------------|-------------|
| Range tested (mg/dL) | 0.01 - 19.5 | 0.02 - 19.4 |
| Range found (mg/dL) | 0.01 - 19.5 | 0.02 - 17.4 |
| Recommended measuring range (mg/dL) | 0.07 - 13.8 | 0.07 - 13.8 |

The quadratic model is significant for both sample types.

Linear Regression Equation for Serum y = 1.0000x ~ 0.0000 r2 = 0.9944

Linear Regression Equation for Plasma r2 = 0.9977 y = 1.0000x - 0.0000

Traceability, stability, and expected values

This method has been standardized against the manual test performance using the Doumas method.

The reagent has been evaluated for transport, shelf-life, open on-board, and calibration stability.

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#### Detection limit LoB. LoD, and LoO studies were performed based upon CLSI EP17-A2.

LoB Protocol: One blank sample was tested in n=5 with two analyzers with three reagent batches for two runs per day across three days.

LoD Protocol: Five low-analyte samples were measured in singlicate on two analyzers with three reagent batches for two runs per day across three days.

LoO Protocol: A low-level sample set of nine was measured in singlicate, using three reagent batches on two analyzers for two runs per day across three days. The LoQ is determined based on precision at 20% CV.

The LoB, LoD, and LoQ claims represent the specifications for each.

LoB claim = 0.05 mg/dL LoD claim = 0.07 mg/dL LoQ claim = 0.07 mg/dL

Analytical specificity interference from endogenous substances

The reagent was evaluated with two endogenous substances, hemoglobin and lipids, for potential interference with the measurement of direct bilirubin.

One pool of human serum was spiked with the interferent. A second pool of human serum contained none. The two pools were mixed in different ratios to yield a dilution series with varying concentrations of the interferent (from 0 to 10).

The endogenous interference data are summarized in the table. The labeling claims the specification, "No significant interference up to an H index of 25," and "No significant interference up to an L index of 750."

Endogenous Interference Summary Data

| | no interference up to this concentration (mg/dl) |
|------------------------|--------------------------------------------------|
| Lipemia low analyte | 1098 |
| Lipemia high analyte | 1100 |
| Hemolysis low analyte | 35 |
| Hemolysis high analyte | 25 |

The lowest L index for which there is no significant interference is 1098. The lowest H index for which there is no significant interference is 25.

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Analytical specificity interference from common drugs

Eighteen commonly used drugs were added to native patient samples and examined for potential interference on measurement with COBAS INTEGRA Bilirubin Direct reagent.

Drug interference testing was performed with serum sample pools at two target concentrations of direct bilirubin, one at a low concentration of ~ 1.8 mg/dL and the second one at a high concentration of ~ 4.9 mg/dL.

Direct bilirubin concentration in all aliquots is measured in triplicate on the COBAS INTEGRA analyzer. The mean value among the triplicates for each aliquot is determined. From the mean values, the percent recovery to the initial value is calculated.

"Phenylbutazone causes falsely low bilirubin results." This statement appears in the labeling. The remaining 17 commonly used drugs produce no interference with BILD2 measurement.

| | Drug | Highest Concentration Shown<br>Not to Interfere with BILD2<br>(mg/L, except Heparin) |
|----|----------------------|--------------------------------------------------------------------------------------|
| 1 | Acetylcystein | 150 |
| 2 | Ampicillin - Na | 1000 |
| 3 | Ascorbic acid | 300 |
| 4 | Ca - Dobesilate | 200 |
| 5 | Cyclosporine A | 5 |
| 6 | Cefoxitin | 2500 |
| 7 | Heparin - Na | 5000 U |
| 8 | Intralipid | 10000 |
| 9 | Levodopa | 20 |
| 10 | Methyldopa + 1.5 | 20 |
| 11 | Metronidazole | 200 |
| 12 | Doxycyclin | 50 |
| 13 | Acetylsalycilic acid | 1000 |
| 14 | Rifampicin | 60 |
| 15 | Acetaminophen | 200 |
| 16 | Ibubrofen | 500 |
| 17 | Theophylline | 100 |

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Method comparison with predicate device

Direct bilirubin values for n=71 human sera samples were obtained using the candidate reagent (y-axis) to the predicate reagent (x-axis) on the COBAS INTEGRA 800 clinical chemistry analyzer. Samples ranged from 0.083 to 13.762 mg/dL and were tested in singlicate. The values were regressed using the Passing/Bablok model to produce the following equation. R2 = 0.9979

y = 1.0490x + 0.0699 mg/dL

Matrix comparison Lithium-heparin, K2-EDTA, and K3-EDTA are permissible anticoagulants for use with this reagent because they do not interfere with recovery of direct bilirubin. 32 tubes were collected per anticoagulant. Plasma results were compared to serum results and percent recovery was determined.

Median Values for Anticoagulant Comparisons

| anticoagulants | median recovery | median absolute<br>deviation(mg/dL) |
|---------------------|-----------------|-------------------------------------|
| Li-Heparin (full) | 102% | +0.02 |
| Li-Heparin (half) | 102% | -0.05 |
| K2-EDTA (full) | 101% | +0.00 |
| K2-EDTA (half) | 101% | -0.02 |
| K3-EDTA (full) | 100% | -0.00 |
| K3-EDTA (half) | 100% | -0.03 |
| Gel Separation Tube | 104% | +0.02 |
| Criteria | 90 to 110% | <0.20 |

Comparisons were also regressed.

| Serum vs. Li-heparin | P/B: y = 0.01 + 1.0179x, | r = 0.9988 |
|----------------------|---------------------------|------------|
| Serum vs. K2-EDTA | P/B: y = -0.01 + 1.0120x, | r = 0.9988 |
| Serum vs. K3-EDTA | P/B: y = -0.03 + 1.0095x, | r = 0.9988 |

Expected values/

Direct bilirubin ≤ 0.20 mg/dL

reference range

Balisteri WF, Shaw LM. Liver function. In: Tietz NW, ed. Fundamentals of Clinical Chemistry. 3th ed. Philadelphia: WB Saunders 1987; 729-761.

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## 510(k) Summary for COBAS INTEGRA Bilirubin Direct Gen.2, Continued and the same of the same of the same of the same of the same of the same of the states of the states of the states of the states of the states of the states of the states of

and the contraction of the comments of the comments of the contraction of the control of

The submitted information in this premarket notification supports a Conclusion substantial equivalence decision.

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Image /page/11/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features the department's name in a circular arrangement around an emblem. The emblem is a stylized representation of an eagle, with three distinct lines forming its body and wings. The eagle is oriented to the right, symbolizing strength and national identity.

#### DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-002

### February 28, 2013

Roche Diagnostics c/o Susan Hollandbeck Regulatory Affairs Consultant 9115 South Hague Road Indianapolis, IN 46250

Re: k123965

Trade/Device Name: COBAS INTEGRA Bilirubin Direct Gen. 2 Reagent Regulation Number: 21 CFR 862.1110 Regulation Name: Bilirubin (total or direct) test system Regulatory Class: Class II Product Code: CIG Dated: December 21, 2012 Received: December 26, 2012

Dear Ms. Hollandbeck:

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 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); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set

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Page 2 - Susan Hollandbeck

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.

If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostics and Radiological Health at [phone]. 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 the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

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 [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,
Carol C. Benson -
S for

Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology. 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): k123965

Device Name: COBAS INTEGRA Bilirubin Direct Gen.2

Indications for Use:

COBAS INTEGRA Bilirubin Direct Gen.2 is an in vitro test for the quantitative determination of direct bilirubin in human serum and plasma on COBAS INTEGRA systems. Measurement of the levels of 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.

Prescription Use X (21 CFR Part 801 Subpart D)

And/Or

Over the Counter Use (21 CFR Part 801 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostics and Radiological Health (OIR)

YungW.Chan -S

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

k123965 510(k)

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