Predicate Devices

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The document describes a reagent system for quantitative determination of bilirubin on automated clinical chemistry analyzers. There is no mention of AI or ML in the intended use, device description, or any other section. The technology described is standard clinical chemistry analysis.

Therapeutic

No
The device is described as an "in vitro diagnostic reagent system" intended for the "quantitative determination of bilirubin concentration in serum and plasma," indicating it is used for diagnostic testing and not for treating a disease or condition.

Diagnostic

Yes
The "Intended Use / Indications for Use" section explicitly states that the devices are "intended for use... for the quantitative determination... if used in the diagnosis of liver, hemolytic hemoatological, and metabolic disorders, including hepatitis and gall bladder block." This indicates a diagnostic purpose.

SaMD (Software as a Medical Device)

No

The device description clearly states it is an "in vitro diagnostic reagent system" intended for use on specific hardware systems (COBAS INTEGRA and Roche/Hitachi systems). This indicates it is a chemical reagent component used with hardware, not a standalone software device.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

Intended Use/Indications for Use: The descriptions explicitly state that the reagent systems are "in vitro diagnostic reagent system intended for use on COBAS INTEGRA systems for the quantitative determination of..." This directly aligns with the definition of an IVD, which is used to examine specimens taken from the human body to provide information for diagnosis, monitoring, or screening.
Measurement of Bilirubin: The purpose of the device is to measure bilirubin levels in serum and plasma. This is a common diagnostic test used to assess liver function and diagnose various medical conditions.
Diagnosis of Disorders: The text explicitly mentions that the measurement of bilirubin levels is used "in the diagnosis of liver, hemolytic hemoatological, and metabolic disorders, including hepatitis and gall bladder block." This further confirms its diagnostic purpose.
Device Description: The description reiterates that the 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," reinforcing its role in laboratory testing.
Predicate Devices: The listing of predicate devices with K numbers (which are FDA premarket notification numbers) indicates that these are medical devices that have gone through regulatory review, a common characteristic of IVDs.

Therefore, based on the provided information, the COBAS INTEGRA and Roche/Hitachi bilirubin reagent systems are clearly intended and used as In Vitro Diagnostic devices.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / 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.

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

Product codes (comma separated list FDA assigned to the subject device)

CIG

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.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

Adults and neonates

Intended User / Care Setting

Not Found

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Not Found

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Not Found

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

K951595, K981632/A001, K981632/A001

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

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.

Summary

0

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

1

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 include
clarification that underfilled lithium heparin sample tubes may
cause elevated results Clarification for reagent handling 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
Submitter
name, address,
contact	Roche Diagnostics
9115 Hague Rd
Indianapolis IN 46250
(317) 521-3723

Contact person: Corina Harper

Date prepared: October 30, 2006 |
| Device Name | Device 1:
Proprietary name: COBAS INTEGRA Bilirubin Direct
Common name: Bilirubin Direct
Classification name: Bilirubin (total or direct) test system

Device 2:
Proprietary name: COBAS INTEGRA Total Bilirubin Special
Common name: Total Bilirubin
Classification name: Bilirubin (total or direct) test system

Device 3:
Proprietary name: Roche/Hitachi Total Bilirubin
Common name: Total Bilirubin
Classification name: Bilirubin (total or direct) test system |

2

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	Classification
Number	Classification Name	Regulation
Citation
	75 Clinical
Chemistry	CIG	Bilirubin (total or direct)
test system	21 CFR 862.1110
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.
Intended use	Device 1: COBAS INTEGRA Bilirubin Direct:
The cassette COBAS INTERGA Bilirubin Direct 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..

Device 2: COBAS INTEGRA Total Bilirubin Special:
The COBAS INTERGA Total Bilirubin Special 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.

Device 3: Roche/Hitachi Total Bilirubin:
For the quantitative determination of total bilirubin in serum and plasma of
adults and neonates on Roche/Hitachi automated clinical chemistry analyzers. | | | |
| Predicate
Device | We claim substantial equivalence to
Device 1: Bilirubin Direct cleared as K951595
Device 2: Total Bilirubin cleared as K981632/A001
Device 3: Total Bilirubin cleared as K981632/A001 | | | |

Continued on next page

3

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 INTEGRA
Bilirubin Direct K951595	COBAS INTEGRA Bilirubin Direct
	Device 2: COBAS INTEGRA Total
Bilirubin Special K981632/A001	COBAS INTEGRA Total Bilirubin Special
	Device 3: Roche/Hitachi Total
Bilirubin K981632/A001	Roche/Hitachi Total Bilirubin
General
Intended Use/
Indications for
Use	Device 1: 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).	Same
	Device 3: 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).	Same
	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.	Same
Specimen	Device 1: serum and plasma	Same
	Device 2: serum and plasma of adults and
neonates	Same
	Device 3: serum and plasma of adults and
neonates	Same
Test Principle
Reference
method	Device 1: Diazo method	Same
	Device 2: Diazo method	Same
	Device 3: Diazo method	Same
Reagent information
Reagent
composition	Device 2: COBAS INTEGRA Total
Bilirubin Special
R1: Sodium acetate buffer 85
mmol/L, Sulfamic acid 110 mmol/L

R2: Hydrochloric acid 100 mmol/L,
Diazonium ion 3 mmol/L | Same |
| | Device 3: Roche/Hitachi Total
Bilirubin
R1: Sodium acetate buffer 85
mmol/L, Sulfamic acid 110 mmol/L

4

.

:

5

.

:

.

:

6

:

7

:

8

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 Direct
K951595 | Modified device:
COBAS INTEGRA Bilirubin Direct |
|-----------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------|
| | COBAS INTEGRA Total Bilirubin
Special K981632/A001 | COBAS INTEGRA Total Bilirubin
Special |
| | Roche/Hitachi Total Bilirubin
K981632/A001 | Roche/Hitachi Total Bilirubin |
| Reagent information | | |
| Reagent
composition | Device 1: COBAS INTEGRA
Bilirubin Direct
R1: Sulfanic acid 35 mmol/L, Oxalic
acid 40 mmol/L, HEDTA 4.0
mmol/L, pH 1.1 | R1: Sulfanic acid 35 mmol/L, Oxalic
acid 40 mmol/L, HEDTA 4.0
mmol/L, pH 1.2 |
| | R2: Sodium nitrite 3.9 mmol/L, pH
6.0 | Same |
| Traceability | Device 1:
Standardized against the manual test
performance using the Jendrassic
Grof method | Standardized against the Doumas
reference method |
| Endogenous
interferences | Device1:
Hemolysis: even slight hemolysis
interferes with the test
Lipemia: : even slight lipemia
interferes with the test | Hemolysis: No significant
interference up to an H index of 10
Lipemia: No significant interference
up to an L index of 270 |
| | Device 2:
Hemolysis: No significant
interference up to 1000 mg/dL
Lipemia: No significant interference
up to 1800 mg/dL as Intralipid | Hemolysis: No significant
interference up to 1000 mg/dL
Lipemia: No significant interference
up to 1400 mg/dL as Intralipid |

9

| Additional
information for
modifications to
values
assignment
process and
traceability | Direct Bilirubin:
Roche Diagnostics has revised the calibration of the COBAS
INTEGRA Bilirubin Direct method due to ongoing quality assurance
and customer feedback. Traceability was changed to the Doumas
method, and the concurrent change in Quality Control limits for this
method were intended to minimize or eliminate any discrepancies seen
by the users. The impact of using new setpoints was shift to direct
bilirubin values lower when compared to the values obtained using
previous setpoints. The shift occurred in both controls and patient
specimens.
The revised setpoints or revised values for controls and its clinical
significance were communicated to the customers via Reagent
Bulletins in April 2002, March 2004, November 2004.

Another communication regarding low recovery of
Precinom U/Precinorm U Plus controls was communicated in May
2006. |
|----------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | 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 available on the COBAS INTEGRA and Roche/Hitachi
analyzers. This change was triggered by internal investigation and
customer feedback. The Roche Diagnostics US Standardization
laboratory has reassigned the values based on a new procedure which
maintained the same traceability to the Doumas method. The results
were verified by using US reference laboratory.
The revised setpoints or revised values for controls were
communicated to the customers via a Reagent Bulletins in August
2006. |
| Proposed
Labeling | Proposed labeling sufficient to describe the device, its intended use, and the
directions for use can be found in Section V. We believe the proposed version
of the device labeling presented contains all of the technical information
required per 21 CFR 809.10. |
| Validation and
Design Control | Development activities were conducted under appropriate design control
procedures and the overall product specifications were met. The Declaration
of Conformity with Design Controls and Results of Risk Analysis are
provided in Section 5.1. Analytical Performance. |
| Confidentiality | Roche Diagnostics Corporation requests that the FDA not disclose the nature
or existence of this submission until the substantial equivalence decision has
been reached. |

10

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

11

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).

12

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

13

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.

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

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

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