October 30, 2018

Ortho-Clinical Diagnostics, Inc.

Marlene Hanna
Director, Regulatory Affairs
100 Indigo Creek Drive
Rochester, NY 14626

Re: K182063
Trade/Device Name: VITROS Chemistry Products CRBM Slides
VITROS Chemistry Products CREA Slides
VITROS Chemistry Products TBIL Slides
VITROS XT 7600 Integrated System
Regulation Number: 21 CFR 862.1225
Regulation Name: Creatinine test system
Regulatory Class: Class II
Product Code: JFY, KLT, CIG, JJE
Dated: July 30, 2018
Received: August 1, 2018

Dear Marlene Hanna:

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. Although this letter refers to your product as a device, please be aware that
some cleared products may instead be combination products. The 510(k) Premarket Notification Database
located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination
product submissions. The general controls provisions of the Act include requirements for annual registration,
listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and
adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We
remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be
subject to additional controls. Existing major regulations affecting your device can be found in the Code of
Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements
concerning your device in the Federal Register.

U.S. Food & Drug Administration

10903 New Hampshire Avenue Doc ID# 04017.03.01
Silver Spring, MD 20993
www.fda.gov
K182063 - Marlene Hanna Page 2

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 and Part 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR
803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see
https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.htm); good
manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820)
for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if
applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-
1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part
807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part
803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.

For comprehensive regulatory information about medical devices and radiation-emitting products, including
information about labeling regulations, please see Device Advice
(https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn
(http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and
Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website
(http://www.fda.gov/DICE) for more information or contact DICE by email ([email protected]) or phone
(1-800-638-2041 or 301-796-7100).

Sincerely,

Kellie B. Kelm -S
GPS Courtney H. Lias, Ph.D.
Director
Division of Chemistry and Toxicology Devices
Office of In Vitro Diagnostics
and Radiological Health
Center for Devices and Radiological Health

Enclosure
 DEPARTMENT OF HEALTH AND HUMAN SERVICES Form Approved: OMB No. 0910-0120
Food and Drug Administration Expiration Date: 06/30/2020
Indications for Use See PRA Statement below.

510(k) Number (if known)

k182063

Device Name
VITROS Chemistry Products CRBM Slides
VITROS Chemistry Products CREA Slides
VITROS Chemistry Products TBIL Slides VITROS XT 7600 Integrated System
Indications for Use (Describe)

1. VITROS Chemistry Products CRBM Slides: Rx Only. For in vitro diagnostic use only. VITROS Chemistry Products
CRBM Slides quantitatively measure carbamazepine (CRBM) concentration in serum and plasma using VITROS
250/350/950/5,1 FS and 4600 Chemistry Systems and the VITROS 5600/ XT 7600 Integrated System. Measurements
obtained are used in monitoring levels of carbamazepine to help ensure appropriate therapy.

2. VITROS Chemistry Products CREA Slides: Rx Only. For in vitro diagnostic use only. VITROS Chemistry Product
CREA Slides quantitatively measure creatinine (CREA) concentration in serum, plasma, and urine using VITROS
250/350/950/5,1 FS and 4600 Chemistry Systems and the VITROS 5600/ XT 7600 Integrated System. Creatinine
measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation
basis for measuring other urine analytes.

3. VITROS Chemistry Products TBIL Slides: Rx Only. For in vitro diagnostic use only. VITROS Chemistry Products
TBIL Slides quantitatively measure total bilirubin (TBIL) concentration in serum and plasma using VITROS
250/350/950/5,1 FS and 4600 Chemistry Systems and the VITROS 5600/ XT 7600 Integrated System. Measurements of
the levels of bilirubin are used in the diagnosis and treatment of liver, hemolytic hematological and metabolic disorders,
including hepatitis and gall bladder block.

4. VITROS XT 7600 Integrated System: Rx Only. For in vitro diagnostic use only. The VITROS XT 7600 Integrated
System is intended for use in the measurement of a variety of analytes of clinical interest.

Type of Use (Select one or both, as applicable)

Prescription Use (Part 21 CFR 801 Subpart D) Over-The-Counter Use (21 CFR 801 Subpart C)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.
*DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.*
The burden time for this collection of information is estimated to average 79 hours per response, including the
time to review instructions, search existing data sources, gather and maintain the data needed and complete
and review the collection of information. Send comments regarding this burden estimate or any other aspect
of this information collection, including suggestions for reducing this burden, to:
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Office of Chief Information Officer
Paperwork Reduction Act (PRA) Staff
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“An agency may not conduct or sponsor, and a person is not required to respond to, a collection of
information unless it displays a currently valid OMB number.”

FORM FDA 3881 (7/17) Page 1 of 1 PSC Publishing Services (301) 443-6740 EF
Traditional 510(k)
VITROS XT 7600 System

5 510(k) Summary Information

This summary of 510(k) safety and effectiveness information is being submitted in accordance
with the requirements of SMDA 1990 and
21 CFR 807.92.

The assigned 510(k) number is: k182063

Submitter’s Information
Ortho-Clinical Diagnostics, Inc.
100 Indigo Creek Drive
Rochester, New York 14626-5101
Phone: (585) 453-4041
Fax: (585) 453-3368

Contact Person:
Marlene Hanna, RAC
Director, Regulatory Affairs

Date of Preparation: July 30, 2018

Device Proprietary Name(s):

VITROS Chemistry Products CRBM Slides

VITROS Chemistry Products CREA Slides
VITROS Chemistry Products TBIL Slides
VITROS XT 7600 Integrated System

Common Names:
Carbamazepine assay
Creatinine assay
Total bilirubin assay
Clinical chemistry analyzer

Classification Names
VITROS Product Class Regulation Section Panel
Code
CRBM KLT Class II 21 CFR 862.3645 Neuroleptic drugs radioreceptor Clinical
assay test system. Toxicology
CREA JFY Class II 21 CFR 862.1225 creatinine test system Clinical
Chemistry
TBIL CIG Class II 21 CFR 862.1110 Bilirubin (total or direct) test system. Clinical
Chemistry
XT 7600 JJE Class I 21 CFR 862.2160 Discrete photometric chemistry Clinical
analyzer for clinical use Chemistry

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Predicate Device(s)

No. New Devices Predicate Devices Predicate Device

FDA 510(k)
Number
1 VITROS Chemistry VITROS Chemistry k160495
Products CRBM Slides Products CRBM Slides
2 VITROS Chemistry VITROS Chemistry k063591
Products CREA Slides Products CREA Slides
3 VITROS Chemistry VITROS Chemistry k840880
Products TBIL Slides Products TBIL Slides
4 VITROS XT 7600 VITROS 5600 k081543
Integrated System Integrated System

Intended Use Statement(s)

1. VITROS Chemistry Products CRBM Slides

Rx Only. For in vitro diagnostic use only. VITROS Chemistry Products CRBM Slides
quantitatively measure carbamazepine (CRBM) concentration in serum and plasma using
VITROS 250/350/950/5,1 FS and 4600 Chemistry Systems and the VITROS 5600/ XT 7600
Integrated System. Measurements obtained are used in monitoring levels of carbamazepine to
help ensure appropriate therapy.

2. VITROS Chemistry Products CREA Slides

Rx Only. For in vitro diagnostic use only. VITROS Chemistry Product CREA Slides
quantitatively measure creatinine (CREA) concentration in serum, plasma, and urine using
VITROS 250/350/950/5,1 FS and 4600 Chemistry Systems and the VITROS 5600/ XT 7600
Integrated System. Creatinine measurements are used in the diagnosis and treatment of renal
diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine
analytes.

3. VITROS Chemistry Products TBIL Slides

Rx Only. For in vitro diagnostic use only. VITROS Chemistry Products TBIL Slides
quantitatively measure total bilirubin (TBIL) concentration in serum and plasma using VITROS
250/350/950/5,1 FS and 4600 Chemistry Systems and the VITROS 5600/ XT 7600 Integrated
System. Measurements of the levels of bilirubin are used in the diagnosis and treatment of liver,
hemolytic hematological and metabolic disorders, including hepatitis and gall bladder block.

4. VITROS XT 7600 Integrated System

Rx Only. For in vitro diagnostic use only. The VITROS XT 7600 Integrated System is intended
for use in the measurement of a variety of analytes of clinical interest.

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VITROS XT 7600 System

Device Description

The VITROS XT 7600 Integrated System is a fully automated, computer controlled, clinical
chemistry and immunodiagnostic analyzer intended for the in vitro determination of a variety of
general chemistries, therapeutic drugs, drugs of abuse, proteins, infectious diseases, as well as
cardiac, metabolic, thyroid, anemia, and oncology markers in biological fluids such as serum,
plasma, urine and cerebral spinal fluid. The System operates in conjunction with reagents,
calibrators and controls designed for use with the System in the MicroSlide, MicroTip or
MicroWell format.

The VITROS Chemistry MicroSlide range of products (in this case VITROS Chemistry Products
CRBM Slides, VITROS Chemistry Products CREA Slides, and VITROS Chemistry Products
TBIL Slides), are combined with the VITROS XT 7600 Integrated System to perform the
VITROS CRBM, CREA, and TBIL assays.

Comparison to Predicate Devices

The following tables show similarities and differences between the new and predicate devices.

Table 1 VITROS Chemistry Products CRBM Slides

Similarities
Device Candidate Predicate Device
Characteristic VITROS CRBM Slides VITROS CRBM
Slides
k160495
Intended Use Rx Only. For in vitro diagnostic Same
use only. VITROS Chemistry
Products CRBM Slides
quantitatively measure
carbamazepine (CRBM)
concentration in serum and plasma.

Basic principle Multiple-point Immunorate Same

Reactive Immobilized mouse monoclonal Same
Ingredients anti-carbamazepine antibody
per cm2 0.02 mg; carbamazepine-
horseradish peroxidase conjugate
1.6 ng; and 2-(3,5-dimethoxy-4-
hydroxyphenyl)-4,5-bis(4-
dimethylaminophenyl) imidazole
(leuco dye) 0.02 mg.
Wavelength 670 nm, 540 nm is also used for wash Same
detection
Sample type Serum and plasma Same
Sample volume 11 μL Same

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Differences
Device Candidate Predicate Device
Characteristic VITROS CRBM Slides VITROS CRBM
Slides
k160495
Instrumentation VITROS 250/350/950/5,1 FS and VITROS
4600 Chemistry Systems and the 250/350/950/5,1 FS and
VITROS 5600/ XT 7600 Integrated 4600 Chemistry
System Systems and the
VITROS 5600
Integrated System

Table 2 VITROS Chemistry Products CREA Slides

Similarities
Device Candidate Predicate Device
Characteristic VITROS CREA Slides VITROS CREA Slides
k063591
Intended Use Rx Only. For in vitro diagnostic Same
use only. VITROS Chemistry
Product CREA Slides
quantitatively measure creatinine
(CREA) concentration in serum,
plasma, and urine.

Basic principle Two-point rate Same

Reactive Creatinine amidohydrolase Same
Ingredients (Flavobacterium sp.) 0.20 U; creatine
per cm2 amidinohydrolase (Alcaligenes sp.) 3.6
U; sarcosine oxidase (Bacillus sp.)
0.55 U; peroxidase (horseradish root)
1.6 U and 2- (3,5-dimethoxy-4-
hydroxyphenyl)-4,5-bis(4-
dimethylaminophenyl) imidazole
(leuco dye) 32 µg.
Wavelength 670 nm Same
Sample type Serum, plasma, urine Same
Sample volume 6 L Same

Differences
Device Candidate Predicate Device
Characteristic VITROS CREA Slides VITROS CREA Slides
k063591

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VITROS XT 7600 System

Instrumentation VITROS 250/350/950/5,1 FS and VITROS

4600 Chemistry Systems and the 250/350/950/5,1 FS and
VITROS 5600/ XT 7600 Integrated 4600 Chemistry
System Systems and the
VITROS 5600
Integrated System

Table 3 VITROS Chemistry Products TBIL Slides

Similarities
Device Candidate Predicate Device
Characteristic VITROS TBIL Slides VITROS TBIL
Slides
K840880
Intended Use Rx Only. For in vitro diagnostic use Same
only. VITROS Chemistry Products
TBIL Slides quantitatively measure
total bilirubin (TBIL) concentration in
serum and plasma.
Basic principle Dual wavelength endpoint Same
Reactive Dyphylline 0.5 mg and 4-(N- Same
Ingredients carboxymethylaminosulfonyl) benzene
per cm2 diazonium hexafluorophosphate 57 µg.
Wavelength measured at 2 wavelengths, 460 and Same
540nm
Sample type Serum and plasma Same
Sample volume 10 L Same

Differences
Device Candidate Predicate Device
Characteristic VITROS TBIL Slides VITROS TBIL
Slides k840880
Instrumentation VITROS 250/350/950/5,1 FS and VITROS
4600 Chemistry Systems and the 250/350/950/5,1 FS
VITROS 5600/ XT 7600 Integrated and 4600 Chemistry
System Systems and the
VITROS 5600
Integrated System

Table 4 VITROS XT 7600 Integrated System

Similarities
Device Candidate Predicate Device
Characteristic VITROS XT 7600 System VITROS 5600
System
k081543

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VITROS XT 7600 System

Similarities
Device Candidate Predicate Device
Characteristic VITROS XT 7600 System VITROS 5600
System
k081543
System Features
Intended use For use in the in vitro quantitative, semi- No change
quantitative, and qualitative
measurement of a variety of analytes of
clinical interest, using VITROS
Chemistry Products Slides, VITROS
Chemistry Products MicroTip Reagents
and VITROS Immunodiagnostic
Products Reagents.
Fundamental MicroSlides - Colorimetric, No change
scientific Potentiometric, enzymatic endpoint and
technology Immunorate assays.

MicroTip and MicroWell reagents

The analyzer uses four main detection

systems:
1) Reflection densitometry for
colorimetric and Immunorate
VITROS MicroSlides.
2) Transmission spectrophotometry
for VITROS MicroTip assays.
3) Enhanced chemiluminescent
detection for VITROS MicroWell
assays.
4) Electrometer for VITROS
MicroSlide ion-selective electrode
(ISE) assays.
Operating Sample programming, sampling No change
principle processing, result calculation, result
reporting
Modes of Continuous, Random, STAT No change
operation
Throughput 845 tests per hour No change
User interface Touch screen (17 inch monitor), No change
keyboard, ADD
Sample and Verification to ensure sufficient quantity No change
reagent volume of sample and reagent to run requested
verification assays
On-Board Dilution factor of 1: 400 No change
Dilution Range
Predictive alerts The predictive alerts are logged and are No change
through electronically sent to the equipment
eConnectivity service group real time for monitoring.
e-Connectivity Yes No change

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Similarities
Device Candidate Predicate Device
Characteristic VITROS XT 7600 System VITROS 5600
System
k081543
(remote access)
Lab Information No change
System (LIS) Enabled
VAS Lab Enabled No change
Automation
System (LAS)
Specimen Sampling and Handling
Specimen type Serum, Plasma, Urine, CSF, Whole No change
Blood
Specimen Cups, Primary Sample Collection Tubes No change
containers
Identification Manual entry or Bar Code No change
Specimen Universal Sample Tray No change
handling
Specimen Auto-dilution, repeat and reflex No change
processing capabilities
Automation Supported No change
capabilities:
10.25 mm tube
for pediatric
samples
Sample Quality Yes No change
Monitoring
(hemolysis,
icterus and
turbidity)
Calibration
Calibrators MicroSlide and MicroTip: analyte No change
specific and multiple analytes
MicroWell: analyte specific
Identification MicroSlide and MicroWell: Bar Code or No change
manual entry
MicroTip: Manual entry
Calibration Sample tray can contain Calibrators, QC No change
Programming samples and/or patient samples
Frequency According to the assay Instructions for No change
Use

Calibration Tracking time until calibration No change

Completion completion is displayed to the operator.
Time
Monitoring
Quality Control

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Similarities
Device Candidate Predicate Device
Characteristic VITROS XT 7600 System VITROS 5600
System
k081543
Controls MicroSlide and MicroTip: analyte No change
specific and multiple analyte
performance verifiers
MicroWell: analyte specific and
multiple analyte selling controls and
range verifiers
Review Mode Review Data by Assay and by Event No change
(scroll through multiple assays’ QC
results which were run at the same time)
Identification Manual entry or Bar Code No change
Frequency According to the assay Instructions for No change
Use. User configurable QC expiration
interval.
QC Programmed by assay No change
Programming

Differences
Device Candidate Predicate Device
Characteristic VITROS XT 7600 System VITROS 5600
System
K081543
The following REFL – Reflectometer All modifications
subsystems of SLIN – Slide Incubator pertain solely to the
the VITROS SLSU – Slide Supply MicroSlide
5600 Integrated SAIN – Sample Integrity processing center.
System will be SRME – Sample and Reagent Metering There are no changes
modified SWCT - System Control and Sample being made to the
Processing Software MicroTip and
SWIN – Software Infrastructure MicroWell
SWUI – Graphical User Interface processing centers.
Software
ADDI – Assay Data Disk.

Method Comparison

Method Comparison testing was designed and conducted in accordance with CLSI
EP09-A3, “Measurement Procedure Comparison and Bias Estimation Using Patient Samples;
Approved Guideline – Third Edition” (2013).

Method comparison studies were conducted by testing a minimum of 116 human serum samples
with analyte concentrations across the analytical ranges of carbamazepine, creatinine and total
bilirubin assays on the VITROS XT 7600 Integrated System and the VITROS 5600 Integrated
System (predicate device). In addition, 125 human urine samples were tested for creatinine on the

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candidate and predicate test systems. The results of the regression analyses for each of the assays
are summarized below:

VITROS Regression Slope Intercept Test range Claimed

assay N Analysis Measuring
Range
CRBM
Serum 118 Deming 1.00 0.12 3.1-17.8 3.0-20.0
(ug/mL)
CREA
Passing
Serum 116 0.99 0.00 0.25-13.4 0.15-14.0
Bablock
(mg/dL)
CREA
Passing
Urine 122 0.99 -0.45 3.7-331.0 3.2-346.5
Bablock
(mg/dL)
TBIL
Passing
Serum 125 0.99 0.01 0.14-23.65 0.10-27.00
Bablok
(mg/dL)

In addition to the above mentioned method comparison studies, testing was performed to
determine the precision, linearity, LoB, LoD, LoQ, and Interfering substances of the
representative VITROS assays on the VITROS XT 7600 System.

Precision

Precision studies were conducted following EP05-A3, Evaluation of Precision of Quantitative

Measurement Procedures, Approved Guidelines – Third Edition (2014). The study was
performed by testing a minimum of two Quality control fluids and three human based precision
fluids using the Carbamazepine (CRBM), Creatinine (CREA), and Total Bilirubin (TBIL)
assays.

Samples were analyzed using one VITROS XT 7600 Integrated System over 20 days, with 2
runs per day and 2 replicates per specimen (n=80).

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CRBM Precision Table (Conventional units)

Repeatability Within Lab

Within Day Between Day Between Cal
(Within Run) (Total)
Mean SD SD SD SD SD
Fluid
(ug/mL) N (ug/mL) %CV (ug/mL) %CV (ug/mL) %CV (ug/mL) %CV (ug/mL) %CV
ID
CRBM- 3.9 80 0.13 3.30 0.13 3.30 0.08 2.08 0.03 0.77 0.16 3.98
PP1
CRBM- 4.7 80 0.14 2.97 0.14 3.02 0.00 0.00 0.07 1.40 0.16 3.32
6155-1
CRBM- 10.1 80 0.24 2.38 0.25 2.46 0.00 0.00 0.13 1.25 0.28 2.76
6156-2
CRBM- 11.6 80 0.30 2.57 0.35 2.98 0.00 0.00 0.18 1.56 0.39 3.37
PP3
CRBM- 13.1 80 0.29 2.19 0.35 2.67 0.00 0.00 0.22 1.64 0.41 3.14
5896-3
CRBM- 17.6 80 0.33 1.86 0.37 2.10 0.10 0.57 0.18 1.03 0.42 2.41
PP5

CREA Serum Precision Table (Conventional units)

Repeatability Within Lab

Within Day Between Day Between Cal
(Within Run) (Total)
SD
Mean SD SD SD SD
Fluid ID (mg/dL)
N
(mg/dL)
%CV
(mg/dL)
%CV
(mg/dL)
%CV
(mg/dL)
%CV (mg/dL %CV
)
CREAS- 0.82 80 0.006 0.713 0.009 1.050 0.003 0.364 0.009 1.121 0.013 1.579
5903-1
CREAS- 0.88 80 0.006 0.642 0.007 0.743 0.008 0.954 0.012 1.400 0.016 1.850
PP1
CREAS- 0.99 80 0.007 0.697 0.008 0.829 0.006 0.568 0.014 1.396 0.017 1.720
SRM
CREAS- 5.39 80 0.039 0.716 0.049 0.914 0.058 1.075 0.043 0.804 0.088 1.624
5905-2
CREAS- 9.63 80 0.057 0.594 0.070 0.729 0.049 0.513 0.104 1.079 0.135 1.400
PP2
CREAS- 12.65 80 0.109 0.865 0.109 0.865 0.071 0.563 0.108 0.850 0.169 1.337
PP5

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CREA Urine Precision Table (Conventional units)

Repeatability Within Lab

Within Day Between Day Between Cal
(Within Run) (Total)
Mean SD SD SD SD SD
Fluid ID (mg/dL)
N
(mg/dL)
%CV
(mg/dL)
%CV
(mg/dL)
%CV
(mg/dL)
%CV
(mg/dL)
%CV

CREAU- 55.6 80 0.58 1.05 0.67 1.20 0.43 0.77 0.96 1.72 1.24 2.23
66791-1
CREAU-PP1 78.4 80 1.10 1.40 1.13 1.44 0.35 0.45 0.68 0.86 1.36 1.73
CREAU-URN 88.0 80 0.69 0.79 0.98 1.11 0.29 0.33 0.97 1.10 1.41 1.60
CREAU- 131.2 80 1.67 1.27 1.89 1.44 0.76 0.58 1.78 1.36 2.71 2.06
66792-2
CREAU-PP4 251.8 80 1.99 0.79 2.12 0.84 1.01 0.40 3.11 1.24 3.90 1.55
CREAU-PP5 320.9 80 2.99 0.93 3.49 1.09 1.49 0.46 3.99 1.24 5.51 1.72

TBIL Precision Table (Conventional units)

Repeatability Within Lab

Within Day Between Day Between Cal
(Within Run) (Total)
Mean SD SD SD SD SD
Fluid ID N (mg/dL)
%CV (mg/dL) %CV (mg/dL) %CV (mg/dL) %CV (mg/dL) %CV
(mg/dL)
TBIL-PP1 0.3 80 0.01 4.54 0.02 5.20 0.01 4.25 0.00 0.00 0.02 6.72
TBIL-5903- 1.6 80 0.03 1.68 0.04 2.88 0.01 0.51 0.03 1.84 0.05 3.45
1
TBIL-PP3 6.5 80 0.03 0.52 0.06 0.87 0.06 0.88 0.04 0.64 0.09 1.40
TBIL-5905- 15.3 80 0.10 0.67 0.16 1.05 0.10 0.68 0.15 0.99 0.24 1.60
2
TBIL-PP5 21.6 80 0.17 0.77 0.20 0.92 0.28 1.29 0.00 0.00 0.34 1.58

Linearity
Linearity studies were performed according to CLSI EP06-A, Evaluation of the Linearity of
Quantitative Measurement Procedures: A Statistical Approach Approved Guideline (2003).
VITROS CRBM Slides, VITROS CREA Slides, and VITROS TBIL Slides were tested on the
VITROS XT 7600 Integrated System. A series of eleven proportionally related admixtures of
low and high test fluids were tested to verify linearity; each sample was tested in triplicate, a
minimum of two replicates was acceptable for analysis.
The linearity studies support the claimed measuring ranges for the VITROS CRBM,
VITROS CREA, and VITROS TBIL assays.

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Detection Limits

Detection capability studies for each analyte were evaluated based upon CLSI EP17-A2,
Evaluation of Detection Capability for Clinical Laboratory Measurements Procedures:
Approved Guidelines – Second Edition (2012).

Limit of blank (LoB) studies were performed by testing 4 blank samples. Samples were tested in
replicates of 6 over 3 days, using 3 lots of reagents, 4 samples every day, for a total of 216
observations (72 results per reagent lot). The LoB value for each assay was defined as the highest
value achieved using blank samples with the stated probability (i.e.  = 5%). Since the data for all
assays were non-gaussian, a non-parametric approach was applied that estimates the LoB using
the calculated rank position corresponding to the 95th percentile of the distribution of blank
values observed.”
Limit of detection (LoD) studies were performed by testing 4 pools of human samples with
analyte concentrations close to the expected detection limit for each analyte. Samples were tested
in replicates of 6 over 3 days, using 3 lots of reagents, with the 4 human sample pools every day,
for a total of 216 observations (72 results per reagent lot). The data were analyzed according to
CLSI EP17-A2, using CLSI-approved statistical software Analyse-it version 4.95.4, Method
Validation Edition (Analyse-it Software Limited, Leeds UK). The software calculated LoD
using a pooled SD from the low level fluid results and the input LoB value for the assay,
determined as described above. The LoD value for the assay is the highest resultant value
achieved among the combinations of reagent lots and human pools evaluated, with the stated
probability (i.e. β= 5%).

Limit of Quantitation studies were performed using 4 pools of low level samples with analyte
concentrations close to the expected LoQ of the corresponding assay. Samples were tested in
replicates of 4 over 3 days, using 3 lots of reagents, 4 samples every day, for a total of 144
observations (48 results per reagent lot). Ortho defines LoQ as the lowest concentration with an
imprecision of ≤20% and percent total allowable error < 19% for carbamazepine; imprecision of
≤20% and percent total allowable error < 30% for creatinine in serum and urine, and imprecision
of ≤25% and total allowable error < 0.09 mg/dL for total bilirubin in serum.

The results of the detection capability studies for each assay are presented in the table below.

CARB TBIL Creatinine (mg/dL)

(µg/mL) mg/dL
Serum/plasma Urine
LoB 0.6108 0.0378 0.0933 1.9973
LoD 0.6821 0.0722 0.0991 2.1986
LoQ 2.6860 0.0616 0.1119 2.0060
Claimed LoQ 3.0 0.10 0.15 3.2
Assay Range 3.0-20.0 0.10-27.00 0.15-14.0 3.2-346.5

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Specificity

Interference Testing was performed in accordance with CLSI EP07-A2, Interference Testing in
Clinical Chemistry, Approved Guidance—Second Edition. Clinical and Laboratory Standards
Institute. November 2005, using VITROS CRBM, VITROS CREA and VITROS TBIL assays.

Assays were tested on one VITROS XT 7600 Integrated System (‘VITROS XT 7600, Test
System) and one VITROS 5600 Integrated System (VITROS 5600, Predicate/Control System).
Testing on the representative assays included known chemical interferents, common chemical
substances identified with potential to interfere based upon risk assessment, as well as several
claimed non-interferents. If hemoglobin, bilirubin, and/or intralipid were not previously
identified as known interferents for the representative assays, Hemolysis, Icterus and/or
Turbidity (HIT) indices, respectively, were evaluated during testing. Testing employed “paired-
difference” assessment at a minimum of two analyte levels, as specified by CLSI EP07-A2.

*VITROS Chemistry Products MicroSensor™: Sub-system of analyzer that performs automated

semi-quantitative sample quality index determinations on serum/plasma and cerebrospinal fluid
samples. The sample quality index determinations performed are hemolysis, icterus, and
turbidity; also referred to as ‘HIT indices’ or ‘sample integrity indices’.

Results were evaluated as follows:

Known Interferents: The observed bias was compared to predetermined acceptance criteria (the
Maximum Allowable Interference (MAI)) per product design input, and the Claimed Bias
derived from product claims.
 If the observed bias was within the MAI criteria (either in a positive or negative
direction) and/or less than the Claimed Bias, performance was acceptable.
 If the observed bias was greater than the Claimed Bias, the bias was compared to the 95%
Confidence Limit (one-sided) per CLSI EP07-A2. If the Claimed Bias fell within the
95% Confidence Limit, performance was acceptable.

Potential Interferents and Non-Interfering Substances: The observed bias was compared to the
Maximum Allowable Interference (MAI).
 If the observed bias was within the MAI criteria (either in a positive or negative
direction), performance was acceptable.
 If the observed bias was greater than the MAI the bias was compared to the 95%
Confidence Limit (two-sided) per CLSI EP07-A2. If the Claimed Bias fell within the
95% Confidence Limit, performance was acceptable.

Results demonstrate acceptable bias on the VITROS XT 7600 versus the VITROS 5600 for
currently claimed interferents. The following previously untested analyte/interferent levels
yielded new information for currently claimed interferent compounds as a result of testing:
 3.0 ug/mL CRBM/ 20 mg/dL Bilirubin on CRBM MicroSlides
 3.0 ug/mL CRBM/ 3.0 mg/dL Ethamsylate on CRBM MicroSlides

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 3.0 ug/mL CRBM/ 394 mg/dL Ethanol on CRBM MicroSlides

 3.0 ug/mL CRBM/ 5.0 mg/dL Gentisic Acid on CRBM MicroSlides
 3.0 ug/mL CRBM/ 100 mg/dL N-Acetylcysteine on CRBM MicroSlides
One new interfering substance was identified as a result of testing:
 Tolazamide on CREA(s) MicroSlides
For the above, bias profiles on the VITROS XT 7600 demonstrated equivalent magnitudes to
those using the VITROS 5600, using the noted substances. The Instructions for Use (IFU) for the
VITROS CRBM and CREA assays have been updated to claim the additional interfering levels.

Conclusion
The data presented in this pre-market notification demonstrate that the performance of the
VITROS XT 7600 Integrated System and the VITROS Chemistry Products assays are
substantially equivalent to the cleared predicate devices. The VITROS Chemistry Products
CRBM Slides, VITROS Chemistry Products CREA slides, and VITROS Chemistry Product
TBIL Slides analyzed on the VITROS XT 7600 Integrated System are substantially equivalent to
the VITROS Chemistry Products CRBM Slides (k160495), VITROS Chemistry Products CREA
Slides (k063591), and VITROS Chemistry Products TBIL Slides (k840880) analyzed on the
VITROS 5600 Integrated System.
Equivalence to predicates was demonstrated using commercially available reagents along with
human serum, plasma, and urine samples.
The data presented in the premarket notification provide a reasonable assurance that the VITROS
XT 7600 Integrated System and the VITROS assays are safe and effective for the stated intended
uses.

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