Who is the manufacturer of COBAS INTEGRA 400/800 BILIRUBIN TOTAL?

Roche Diagnostics filed the 510(k) submission for COBAS INTEGRA 400/800 BILIRUBIN TOTAL (K081193).

What is the FDA product code for COBAS INTEGRA 400/800 BILIRUBIN TOTAL?

CIG. It is classified under 21 CFR 862.1110 as a Class 2 device in the Clinical Chemistry panel.

What is the regulatory pathway for COBAS INTEGRA 400/800 BILIRUBIN TOTAL?

510(k) clearance (submission type: Special).

Who can help prepare an FDA 510(k) submission like COBAS INTEGRA 400/800 BILIRUBIN TOTAL?

Innolitics — a medical-device software consultancy — provides regulatory and engineering support for FDA 510(k) submissions. See https://innolitics.com/services/510ks/ or contact https://innolitics.com/contact.

COBAS INTEGRA 400/800 BILIRUBIN TOTAL

Q: What are the predicate devices for COBAS INTEGRA 400/800 BILIRUBIN TOTAL?

Cobas Integra Bilirubin Total (K951595).

K081193 · Roche Diagnostics · CIG · Jan 16, 2009 · Clinical Chemistry

Device Facts

Record ID	K081193
Device Name	COBAS INTEGRA 400/800 BILIRUBIN TOTAL
Applicant	Roche Diagnostics
Product Code	CIG · Clinical Chemistry
Decision Date	Jan 16, 2009
Decision	SESE
Submission Type	Special
Regulation	21 CFR 862.1110
Device Class	Class 2

Intended Use

The Cobas Integra Analyzer and Cobas Integra Reagent Cassettes are intended for the in vitro quantitative determination of analytes in human serum. The system is intended for use in clinical laboratory settings by trained laboratory personnel.

Device Story

Cobas Integra Bilirubin Total reagent performs quantitative in vitro determination of total bilirubin in human serum. System uses diazo method; reagent reacts with bilirubin in serum sample. Automated analyzer processes sample; measures absorbance changes. Used in clinical laboratory settings by trained technicians. Output provided as concentration value (umol/L or mg/dL). Clinicians use results to assess liver function, hemolytic processes, and metabolic disorders. Benefits include rapid, automated diagnostic information for managing hepatobiliary and hematological conditions.

Clinical Evidence

Bench testing only. Precision and method comparison studies performed against an automated laboratory analyzer to validate performance characteristics following modifications.

Technological Characteristics

In vitro diagnostic reagent system using diazo method. Active ingredients include sulfanilic acid, oxalic acid, HEDTA, myristyltrimethylammonium bromide, dodecyltrimethylammonium bromide, and sodium nitrite. Designed for use on Cobas Integra automated analyzers. Measuring range 17-340 umol/L (0.099-20 mg/dL), with automated 1:3 rerun dilution function for higher concentrations. Lower detection limit 1.7 umol/L.

Indications for Use

Indicated for the quantitative determination of total bilirubin in human serum to aid in the 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 Total (K951595)

Related Devices

K131544 — COBAS C BILIRUBIN TOTAL GEN.3 · Roche Diagnostics · Jul 17, 2013
K063543 — COBAS INTEGRA BILIRUBIN SPECIAL AND ROCHE/HITACHI BILRUBIN TOTAL, MODELS 20737496 322, 03261638 190, AND 11822713 226 · Roche Diagnostics Corp. · Dec 22, 2006
K171401 — ELITech Clinical Systems BILIRUBIN TOTAL 4+1, ELITech Clinical Systems BILIRUBIN DIRECT 4+1 · Elitechgroup · Jul 11, 2017
K022339 — TOTAL BILIRUBIN · Abbott Laboratories · Sep 13, 2002

Submission Summary (Full Text)

{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