(263 days)
Not Found
No
The summary describes a standard in vitro diagnostic test using chemical reagents and a clinical chemistry system, with no mention of AI or ML.
No.
The device is an in vitro diagnostic (IVD) reagent for measuring total bilirubin concentration and is used in diagnosis; it does not directly treat or prevent a disease.
Yes
The 'Intended Use / Indications for Use' section explicitly states that "Measurement of the level of bilirubin is used in the diagnosis and treatment of liver, hemolytic hematological, and metabolic disorders". This indicates that the device provides information crucial for diagnosis.
No
The device description explicitly states it is a "reagent" intended for use with "Cobas Integra systems," indicating it is a chemical substance used in conjunction with a hardware analyzer, not a standalone software product.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states it is an "In vitro test for the quantitative determination of the total bilirubin concentration in human serum". This clearly indicates the test is performed outside of the body using biological samples.
- Device Description: The "Device Description" further confirms its use with human serum for quantitative determination, aligning with the definition of an IVD.
- Purpose: The purpose of measuring bilirubin levels is for "diagnosis and treatment of liver, hemolytic hematological, and metabolic disorders", which is a diagnostic purpose.
The information provided strongly supports the classification of this device as an In Vitro Diagnostic.
N/A
Intended Use / Indications for Use
In vitro test for the quantitative determination of the total bilirubin concentration in human serum on Cobas Integra. Bilirubin is formed in the reticuloendothelial system during the degradation of aged erythrocytes. The heme portion from hemoglobin and from other heme-containing proteins is removed, metabolized to bilirubin and transported as a complex with serum albumin to the liver. In the liver, bilirubin is conjugated with glucuronic acid for solubilization and subsequent transport through the bile duct and elimination via the digestive tract. Diseases or conditions which, through hemolytic processes, produce bilirubin faster than the liver can metabolize it, cause the levels of unconjugated (indirect) bilirubin to increase in the circulation. Liver immaturity and several other diseases in which the bilirubin conjugation mechanism is impaired cause similar elevations of circulating unconjugated bilirubin. Bile duct obstruction or damage to hepatocellular structure causes increases in the levels of both conjugated (direct) and unconjugated (indirect) bilirubin in the circulation.
Measurement of the level of bilirubin is used in the diagnosis and treatment of liver, hemolytic hematological, and metabolic disorders, including hepatitis and gall bladder block.
Product codes
CIG
Device Description
The Cobas Integra Bilirubin Total reagent is intended for use with the Cobas Integra systems for the quantitative determination of the total bilirubin concentration in human serum.
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 infants >1 month; Newborns (up to 24 h); Newborns (up to 48 h); Newborns (3 to 5 days)
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)
Precision: Precision was evaluated on Cobas Integra using two human serum pools and following the guidelines of the NCCLS Manual EP5-T2. Reproducibility was determined using human samples and controls in an internal protocol (within-run n=20, between-run n=20).
Level 1: Mean 24.2 umol/L (1.4 mg/dL), CV w/in run 0.45%, CV total 0.80%.
Level 2: Mean 72.5 umol/L (4.2 mg/dL), CV w/in run 0.53%, CV total 0.69%.
Accuracy/Method Comparison:
Total bilirubin values for human serum samples obtained on a Cobas Integra 800 analyzer using the Cobas Integra Bilirubin Total reagent (y) were compared to those determined using Cobas Integra Total Bilirubin Special reagent on a Cobas Integra 800 analyzer (x).
Sample size (n) = 49.
Passing/Bablok: y = 0.956x + 2.113 umol/L, r = 0.999.
Values ranged from 5.49 to 317 umol/L (0.321 to 18.5 mg/dL).
Total bilirubin values for human serum samples obtained on a Cobas Integra 400 analyzer using the Cobas Integra Bilirubin Total reagent (y) were compared to those determined with commercially available reagents for total bilirubin on a Roche/Hitachi 911 analyzer (x).
Sample size (n) = 104.
Linear regression: y = 0.989x - 0.520 umol/L, r = 0.999.
Passing/Bablok: y = 0.991x + 0.219 umol/L.
Values ranged from 3.29 to 282 umol/L (0.192 to 16.5 mg/dL).
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Lower Detection Limit: 1.7 umol/L (0.099 mg/dL). The detection limit represents the lowest measurable analyte level that can be distinguished from zero. It is calculated as the value lying three standard deviations above that of a zero sample (zero sample + 3 SD, within-run precision, n=30).
Predicate Device(s)
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 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.
0
KC81193
Attachment 5
JAN 1 6 2009
510(k) Summary - COBAS INTEGRA 400/800 Bilirubin Total
| Introduction | According to the requirements of 21 CFR 807 92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence |
|---|---|
| Submitter name, address, contact | Roche Diagnostics |
| 9115 Hague Rd | |
| Indianapolis IN 46250 | |
| (317) 521-4569 | |
| Contact person Jennifer Tribbett | |
| Date prepared April 23, 2008 | |
| Device Name | Proprietary name Cobas Integra 400/800 Bilirubin Total |
| Common name Bilirubin (total or direct) test system | |
| Classification name Bilirubin (total or direct) test system | |
| Device Description | The Cobas Integra Bilirubin Total reagent is intended for use with the Cobas Integra systems for the quantitative determination of the total bilirubin concentration in human serum |
| Intended use | In vitro test for the quantitative determination of the total bilirubin concentration in human serum on Cobas Integra Bilirubin is formed in the reticuloendothelial system during the degradation of aged erythrocytes The heme portion from hemoglobin and from other heme-containing proteins is removed, metabolized to bilirubin and transported as a complex with serum albumin to the liver In the liver, bilirubin is conjugated with glucuronic acid for solubilization and subsequent transport through the bile duct and elimination via the digestive tract Diseases or conditions which, through hemolytic processes, produce bilirubin faster than the liver can metabolize it, cause the levels of unconjugated (indirect) bilirubin to increase in the circulation Liver immaturity and several other diseases in which the bilirubin conjugation mechanism is impaired cause similar elevations of circulating unconjugated bilirubin Bile duct obstruction or damage to hepatocellular structure causes increases in the levels of both conjugated (direct) and unconjugated (indirect) bilirubin in the circulation |
Continued on next page
ﻠﺰ
ﺎ ﺑﺤﺮ
1
| Predicate Device | We claim substantial equivalence to the Cobas Integra Bilirubin Total (K951595) |
|---|---|
| Substantial equivalency - device comparison | The table below indicates the similarities and differences between the modified Bilirubin Total and the predicate Bilirubin Total (K951595) |
| Characteristic | Predicate Cobas Integra Bilirubin Total
(K951595) | Modified Cobas Integra
Bilirubin Total |
|---------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | The Cobas Integra Cassette Bilirubin Total
(BIL-T) contains an in vitro diagnostic reagent
system intended for use on Cobas Integra for
the quantitative determination of the total
bilirubin concentration in serum and plasma
(test BIL-T, 0-048) | In vitro test for the
quantitative determination
of the total bilirubin
concentration in human
serum (test BIL-T, 0-048)
on Cobas Integra |
| Indications for Use | Bilirubin is formed in the reticuloendothelial
system during the degradation of aged
erythrocytes The heme portion from
hemoglobin and from other heme-containing
proteins is removed, metabolized to bilirubin
and transported as a complex with serum
albumin to the liver In the liver, bilirubin is
conjugated with glucuronic acid for
solubilization and subsequent transport through
the bile duct and elimination via the digestive
tract Diseases or conditions which, through
hemolytic processes, produce bilirubin faster
than the liver can metabolize it, cause the levels
of unconjugated (indirect) bilirubin to increase
in the circulation Liver immaturity and several
other diseases in which the bilirubin
conjugation mechanism is impaired cause
similar elevations of circulating unconjugated
bilirubin Bile duct obstruction or damage to
hepatocellular structure causes increases in the
levels of both conjugated (direct) and
unconjugated (indirect) bilirubin in the
circulation | Same |
2
| Characteristic | Predicate Cobas Integra Bilirubin Total
(K951595) | | Modified Cobas Integra Bilirubin
Total |
|--------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Assay principle | Diazo method | | Same |
| Active Ingredients | R1 | R2 Test | Same |
| | Sulfanilic Acid
Oxalic Acid
HEDTA
Myristytrimethyl-
ammonium bromide
Dodecyltrimethyl-
ammonium bromide
Sodium nitrite
pH | 35
40
4
2
5
24.5
11 | 13.5 mmol/L
15.4 mmol/L
1.5 mmol/L
0.8 %
1.9 %
3.1 mmol/L
1.4 |
| Measuring range | Test range 0-340 umol/L (0-20 mg/dL)
w/postdilution 0-1020 umol/L (0-60 mg/dL)
Postdilution factor 3 | | 17-340 umol/L (0.099-20 mg/dL)
Determine samples having higher
concentrations via the rerun
function. Dilution of samples via
the rerun function is a 1:3 dilution.
Results from samples diluted by the
rerun function are automatically
multiplied by a factor of 3. |
| | Sensitivity: The sensitivity is defined as the
change of analytical response (ΔA) per unit
change in analyte concentration at a
pathlength of 1 cm. The sensitivity is 2.9 x
103 ΔA per umol/L of total bilirubin (5.0 x
10-2 ΔA per mg/dL of bilirubin) | | Lower Detection Limit: 1.7 umol/L
(0.099 mg/dL). The detection limit
represents the lowest measurable
analyte level that can be
distinguished from zero. It is
calculated as the value lying three
standard deviations above that of a
zero sample (zero sample + 3 SD,
within-run precision, n=30). |
| Characteristic | Predicate Cobas Integra Bilirubin Total
(K951595) | Modified Cobas Integra Bilirubin Total | |
| Precision | Precision was evaluated on Cobas Integra
using two human serum pools and following
the guidelines of the NCCLS Manual EP5-T2 | Reproducibility was determined using human
samples and controls in an internal protocol
(within-run n=20, between-run n=20) The
following results were obtained | |
| | Level 1
Level 2 | Level 1
Level 2 | |
| | Mean
$24.2$ umol/L
( $1.4$ mg/dL) | Mean
$24.2$ umol/L
( $1.4$ mg/dL) | |
| | $72.5$ umol/L
( $4.2$ mg/dL) | $72.5$ umol/L
( $4.2$ mg/dL) | |
| | CV w/in run
$0.46$ % | CV w/in run
$0.45$ % | |
| | CV day/day
$0.48$ % | $0.53$ % | |
| | CV total
$0.78$ % | CV total
$0.80$ % | |
| Accuracy | Accuracy Total bilirubin values for human
sera and plasma samples obtained on Cobas
Integra with the cassette bilirubin total were
compared to those determined with reagents
for total bilirubin on Cobas Mira and the
commercially available alternative clinical
chemistry system Samples were measured
in duplicate Sample size (n) represents all
replicates Values ranged from $1.7$ to $350.6$
umol/L ( $0.1$ to $20.5$ mg/dL)
Cobas Mira
Sample size (n) $208$
Corr Coefficient (r) $0.999$
( $r_s$ ) $0.985$
Lin Regression $y = 1.00x + 1.2$ umol/L
Passing Bablock $y = 1.00x + 0.6$ umol/L
Alternative System
Sample size (n) $210$
Corr Coefficient (r) $0.999$
( $r_s$ ) $0.972$
Lin Regression $y = 0.93x + 0.8$ umol/L
Passing Bablock $y = 0.93x + 0.4$ umol/L | Method Comparison Total bilirubin values for
human serum samples obtained on a Cobas
Integra 800 analyzer using the Cobas Integra
Bilirubin Total reagent (y) were compared to
those determined using Cobas Integra Total
Bilirubin Special reagent on a Cobas Integra 800
analyzer (x)
Cobas Integra 800 analyzer
Sample size (n) = $49$
Passing/Bablok
$y = 0.956x + 2.113$ umol/L
$r = 0.999$
Values ranged from $5.49$ to $317$ umol/L ( $0.321$
to $18.5$ mg/dL)
Total bilirubin values for human serum samples
obtained on a Cobas Integra 400 analyzer using
the Cobas Integra Bilirubin Total reagent (y)
were compared to those determined with
commercially available reagents for total
bilirubin on a Roche/Hitachi 911 analyzer (x)
Roche/Hitachi 911 analyzer
Sample size (n) = $104$
Linear regression
$y = 0.989x - 0.520$ umol/L
$r = 0.999$
Passing/Bablok
$y = 0.991x + 0.219$ umol/L
Values ranged from $3.29$ to $282$ umol/L ( $0.192$
to $16.5$ mg/dL) | |
| Characteristic | Predicate Cobas Integra Bilirubin Total
(K951595) | Modified Cobas Integra Bılırubın Total | |
| Expected
Values | Adults and infants >1month
3 4–17 umol/L (0 2–1 0 mg/dL) | Same | |
| | Newborns (up to 24 h)
34-103 umol/L (2 0 – 6 0 mg/dL) | | |
| | Newborns (up to 48 h)
103-171 umol/L (6 0 –10 0 mg/dL) | | |
| | Newborns (3 to 5 days)
68 – 137 umol/L (4 0 – 8 0 mg/dL) | | |
| | Note It is recommended that each
laboratory establishes and maintains its
own reference ranges and that the values
given here are used as a guideline only | Each laboratory should investigate the
transferability of the expected values to its
own patient population and if necessary
determine its own reference range | |
3
、「 .1
4
5
| Characteristic | Predicate Cobas Integra Bilirubin
Total (K951595) | Modified Cobas Integra Bilirubin
Total |
|-------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Limitations –
interference | Hemolysis Avoid hemolyzed
specimens Even slight hemolysis
interferes with the test
Lipemia Avoid lipemic specimens
Even slight lipemia interferes with the
test
Drugs Of the drugs tested in vitro,
propranolol and theophyline cause
artificially low total bilirubin values
at the tested drug level | Hemolysis No significant
interference up to an H index of 10
(approximate hemoglobin
concentration 6 umol/L or 10
mg/dL)
Lipemia (Intralipid): No significant
interference up to an L index of 9
There is a poor correlation between
the L index (corresponds to
turbidity) and triglycerides
concentration
Drugs Therapeutic drug
interference was tested according to
the recommendations of VDGH
No interference was found
Exception Propranolol and
theophylline cause artificially low
total bilirubin values at the tested
drug level Hydroxocobalamin
(Cyanokit) may cause false-high
results
Other In very rare cases
gammopathy, in particular type
IgM (Waldenstroms
macroglobulinemia) may cause
unreliable results |
バー
6
Image /page/6/Picture/1 description: The image is a seal for the Department of Health & Human Services USA. The seal is circular, with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" arranged around the perimeter of the circle. In the center of the seal is an emblem that resembles a stylized bird or eagle with three wing-like shapes. The emblem is black, and the text is also black against a white background.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
JAN 1 6 2009
Roche Diagnostics c/o Jennifer Tribbett Regulatory Affairs Principal 9115 Hague Road Indianapolis, IN 46250
Re K081193
Trade/Device Name Roche COBAS Integra Bılırubın Total (BIL-T) Regulation Number 21 CFR 862 1110 Regulatıon Name Bılırubın (total or dırect) test system Regulatory Class Class II Product Code CIG Dated December 18, 2008 Received December 19, 2008
Dear Ms Tribbett
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 lımıted to registration and lıstıng (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)
7
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 (301) 594-3084 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 1900 of Small Manufacturers, International and Consumer Assistance at tts tolli-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http //www fda gov/cdrh/dsma/dsmamam html
- 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 -
Sincerely yours,
Coy C. He
Courtney C Harper, Ph D Acting Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
8
Indication for Use
510(k) Number (if known) K081193
Device Name Roche COBAS Integra Bilirubin Total (BIL-T)
Indication For Use
In vitro test for the quantitative determination of the total bilirubin concentration in human serum on COBAS Integra systems
Measurement of the level of bilirubin is used in the diagnosis and treatment of liver, hemolytic hematological, and metabolic disorders, including hepatitis and gall bladder block
Prescription Use _XXX (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 Diagnostic Device Evaluation and Safety (OIVD)
Carol C. Benson
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K081193
Page 1 of 1