(49 days)
No
The summary describes a chemical reagent-based in vitro diagnostic test for measuring bilirubin levels. There is no mention of AI, ML, image processing, or any computational analysis beyond standard quantitative measurement and statistical analysis of results.
No
Explanation: This device is an in vitro diagnostic test designed to measure total bilirubin levels in serum and plasma, which is used for diagnosis and treatment monitoring rather than direct therapeutic intervention.
Yes.
The "Intended Use / Indications for Use" section states that the measurement of bilirubin levels is used "in the diagnosis and treatment of liver, hemolytic, hematological, and metabolic disorders, including hepatitis and gall bladder block," indicating its role in diagnosis.
No
The device is a reagent kit for an in vitro diagnostic test, which is a physical product containing chemical components, not software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states that the device is an "in vitro test for the quantitative determination of total bilirubin in serum and plasma". This clearly indicates that the test is performed outside of the body using biological samples.
- Device Description: The description details the reagents used to perform the test on serum and plasma samples.
- Measurement of Biomarkers: The device measures the level of total bilirubin, which is a biomarker used in the diagnosis and treatment of various medical conditions.
- Performance Studies: The document describes performance studies (precision, linearity, detection limit, analytical specificity, method comparison, matrix comparison) which are typical for IVD devices to demonstrate their analytical performance.
- Predicate Device: The mention of a "Predicate Device(s)" with a K number (K063543) is a strong indicator that this device is being compared to a previously cleared IVD device, a common practice in regulatory submissions for IVDs.
All of these points align with the definition and characteristics of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
cobas c Bilirubin Total Gen.3 is an in vitro test for the quantitative determination of total bilirubin in serum and plasma of adults and neonates on Roche/Hitachi cobas c systems. Measurement of the levels of bilirubin, an organic compound formed during the normal and abnormal destruction of red blood cells, is used in the diagnosis and treatment of liver, hemolytic, hematological, and metabolic disorders, including hepatitis and gall bladder block.
Product codes
CIG
Device Description
cobas c Bilirubin Total Gen.3 reagent provides quantitative measurement of the total bilirubin that is present in serum and plasma of adults and neonates. Reagents are packaged in a cassette with two bottles labeled with their instrument positioning, R1 (Reagent 1) and R2 (Reagent 2). R1 contains detergent, buffer, and stabilizers at pH 1.0. R2 is a 3,5-dichlorophenyl diazonium salt: ≥ 1.35 mmol/L.
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)
Precision Study:
Study type: Precision/Reproducibility according to CLSI EP5-A2.
Sample size: Human sera samples (0.51, 17.7, and 31.8 mg/dL) and two serum-based control samples.
Design: Two aliquots per run, two runs per day for 21 days.
Key results:
Repeatability Summary:
PCCC1: Total Mean 0.90 mg/dL, Within Run Imprecision SD 0.02 mg/dL, CV% 2.1
PCCC2: Total Mean 3.09 mg/dL, Within Run Imprecision SD 0.02 mg/dL, CV% 0.6
Human Serum 1: Total Mean 0.51 mg/dL, Within Run Imprecision SD 0.01 mg/dL, CV% 2.9
Human Serum 2: Total Mean 17.7 mg/dL, Within Run Imprecision SD 0.10 mg/dL, CV% 0.6
Human Serum 3: Total Mean 31.8 mg/dL, Within Run Imprecision SD 0.14 mg/dL, CV% 0.4
Intermediate Precision:
PCCC1: Total Mean 0.90 mg/dL, Total Imprecision SD 0.02 mg/dL, CV% 2.1
PCCC2: Total Mean 3.09 mg/dL, Total Imprecision SD 0.03 mg/dL, CV% 0.8
Human Serum 1: Total Mean 0.51 mg/dL, Total Imprecision SD 0.02 mg/dL, CV% 3.3
Human Serum 2: Total Mean 17.7 mg/dL, Total Imprecision SD 0.14 mg/dL, CV% 0.8
Human Serum 3: Total Mean 31.8 mg/dL, Total Imprecision SD 0.18 mg/dL, CV% 0.6
Linearity Study:
Study type: Linearity/Assay Reportable Range according to CLSI EP6-A.
Sample size: Two separate dilution series (serum and plasma) with thirteen levels for plasma and fourteen levels for serum.
Design: One batch of reagent, one run, samples measured in triplicate. Lithium-heparin used for plasma.
Key results:
Measuring Ranges Supported:
Plasma: Range tested 0.12-39.0 mg/dL, Range found 0.12-39.0 mg/dL, Recommended measuring range 0.15-35.1 mg/dL.
Serum: Range tested 0.12-38.9 mg/dL, Range found 0.12-38.9 mg/dL, Recommended measuring range 0.15-35.1 mg/dL.
Linear Regression Equation for Serum: y=1.0021x-0.0317, r2 = 0.999881
Linear Regression Equation for Plasma: y = 1.0014x - 0.0232, r2 = 0.999954
Detection Limit Study:
Study type: LoB, LoD, and LoQ studies based on CLSI EP17-A2.
Design:
LoB Protocol: One blank sample tested in n=5 on two analyzers with three reagent batches for six runs per day across three days.
LoD Protocol: Five low-analyte samples measured in singlicate on two analyzers with three reagent batches for six runs per day across three days.
LoQ Protocol: A low-level sample set of nine measured in singlicate, using three reagent batches on two analyzers for six runs per day across three days.
Key results:
LoB claim = 0.10 mg/dL
LoD claim = 0.15 mg/dL
LoQ claim = 0.15 mg/dL
Analytical Specificity - Endogenous Substances Interference Study:
Study type: Interference from endogenous substances (hemoglobin, lipids, indican).
Sample size: One pool of human serum spiked with interferent, a second pool of human serum without interferent.
Design: Two pools mixed in different ratios to yield a dilution series. Interference tested at two levels of bilirubin.
Key results:
Lipemia: No significant interference up to an L index of 1000. Acceptance criteria: ≤± 0.10 mg/dL for samples ≤ 1 mg/dL or ≤± 10% for samples > 1 mg/dL.
Hemolysis HbA: No significant interference up to an H index of 800. Acceptance criteria: ≤±0.20 mg/dL for samples ≤ 2 mg/dL or ≤± 10% for samples > 2 mg/dL.
Hemolysis HbF (for neonates): No significant interference up to an H index of 1000. Acceptance criteria: ≤± 0.10 mg/dL for samples ≤ 1 mg/dL or ≤ ± 10% for samples > 1 mg/dL.
Indican: No significant interference from indican up to 3 mg/dL. Acceptance criteria: ≤± 0.10 mg/dL for samples ≤ 1 mg/dL or ≤± 10% for samples > 1 mg/dL.
Analytical Specificity - Common Drugs Interference Study:
Study type: Interference from common drugs.
Sample size: Fifteen commonly used drugs. Serum sample pools.
Design: Tested at two target concentrations of total bilirubin (~1.0 mg/dL and ~14.0 mg/dL). Total bilirubin measured in triplicate.
Key results: Highest Concentration Shown Not to Interfere: Acetylcystein (150 mg/L), Ampicillin - Na (1000 mg/L), Ascorbic acid (300 mg/L), Phenylbutazone (400 mg/L), Cyclosporine A (5 mg/L), Cefoxitin (2500 mg/L), Levodopa (20 mg/L), Methyldopa + 1.5 (20 mg/L), Metronidazole (200 mg/L), Doxycyclin (50 mg/L), Acetylsalycilic acid (1000 mg/L), Rifampicin (60 mg/L), Acetaminophen (200 mg/L), Ibubrofen (500 mg/L), Theophylline (100 mg/L).
Acceptance criteria: Difference in recovery to the reference sample: ≤± 10%.
Adult Method Comparison with Predicate Device:
Study type: Method comparison.
Sample size: n=131 human sera adult samples.
Design: Candidate reagent (y-axis) compared to predicate reagent (x-axis) on Roche/Hitachi cobas c 501 analyzer. Samples tested in singlicate. Values regressed using Passing/Bablok model.
Key results: Candidate sample concentrations ranged from 0.18 to 30.38 mg/dL. Regression equation: y = 0.959x + 0.091 mg/dL, r = 0.9997.
Matrix Comparison Study:
Study type: Evaluation of permissible anticoagulants.
Sample size: 35 tubes collected per anticoagulant.
Design: Plasma results compared to serum results, percent recovery determined.
Key results: Li-Heparin and K2-EDTA do not interfere.
Claimed Measuring Range: 0.15 - 35.1 mg/dL.
Acceptance criteria: For sample concentrations ≤ 0.99 mg/dL, deviation must be ≤ ± 0.10 mg/dL. For sample concentrations > 0.99 mg/dL, deviation must be ≤± 10%.
Method comparisons with plasma vs serum:
Serum vs. Li-heparin > P/B: y = 1.000x + 0.000, r = 0.9998.
Serum vs. K2-EDTA: Not provided in full, but implied to be comparable.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Not Found. Precision, Linearity, Detection Limits, and Interference data provided.
Predicate Device(s):
Reference Device(s):
K981632, K060373/A001, K101456, K042389, K102016
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
Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA logo on the right. The FDA logo features the letters 'FDA' in a blue square, followed by the words 'U.S. FOOD & DRUG ADMINISTRATION' in blue text.
March 14, 2019
Roche Diagnostics Lisa Klinedinst 9115 South Hague Road Indianapolis, IN 46250
Re: K131544
Trade/Device Name: cobas c Bilirubin Total Gen.3 Regulation Number: 21 CFR 862.1110 Regulation Name: Bilirubin (total or direct) test system Regulatory Class: Class II Product Code: CIG, MOM Dated: May 28, 2013 Received: May 29, 2013
Dear Lisa Klinedinst:
This letter corrects our substantially equivalent letter of July 17, 2013.
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. 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.
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
1
801 and Part 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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 mediation-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 (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Kellie B. Kelm -S
Courtney H. Lias, Ph.D. for Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known): K131544
Device Name: cobas c Bilirubin Total Gen.3
Indications for Use:
cobas c Bilirubin Total Gen.3 is an in vitro test for the quantitative determination of total bilirubin in serum and plasma of adults and neonates on Roche/Hitachi cobas c systems. Measurement of the levels of bilirubin, an organic compound formed during the normal and abnormal destruction of red blood cells, is used in the diagnosis and treatment of liver, hemolytic, hematological, and metabolic disorders, including hepatitis and gall bladder block.
Prescription Use X (21 CFR Part 801 Subpart D) And/Or
Over the Counter Use (21 CFR Part 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostics and Radiological Health (OIR)
Yung W. Chan -S
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K131544
Page 1 of __ 1_
3
016_510k Summary
ﺎ ﺳﺮ
510(k) Summary for cobas c Bilirubin Total Gen.3
JUL 1 7 2013
| Date prepared: | July 17, 2013 | |||
|---|---|---|---|---|
| Purpose of | ||||
| submission | Roche Diagnostics hereby submits this 510(k) to provide FDA with | |||
| notification of intent to market a new device named cobas c Bilirubin Total | ||||
| Gen.3 reagent. All data in this submission was generated on the cobas c 501 | ||||
| analyzer. |
This candidate device is a new reagent that was developed by Roche
Diagnostics. The previous generation of reagent, Total Bilirubin, was cleared
in 510(k) K063543 and serves as the predicate device. The candidate and
predicate devices use the same calibrator and controls. Only the reagents
differ. This submission presents data to support clearance of this new
reagent. | | | |
| Measurand | Total Bilirubin | | | |
| Type of test | Quantitative colorimetric method | | | |
| Applicant | Lisa K. Klinedinst
Roche Diagnostics
9115 South Hague Road
Indianapolis, IN 46250
Telephone: (317) 521-1942
Fax: (317) 521-2324
Email: Lisa.Klinedinst@roche.com | | | |
| Candidate
device names | Proprietary name:
cobas c Bilirubin Total Gen.3
Common name:
Bilirubin Total Gen.3 | | | |
| Regulatory
information | Product Code | Classification | Regulation | Panel |
| | CIG | Class II | 21 CFR 862.1110
(Bilirubin (total or direct)
test system) | Clinical
Chemistry |
Continued on next page
।
4
| Intended use | In vitro test for the quantitative determination of total bilirubin in serum and plasma of adults and neonates on Roche/Hitachi cobas c systems. |
|---|---|
| Indications for use | cobas e Bilirubin Total Gen.3 is an in vitro test for the quantitative determination of total bilirubin in serum and plasma of adults and neonates on Roche/Hitachi cobas c systems. Measurement of the levels of bilirubin, an organic compound formed during the normal and abnormal destruction of red blood cells, is used in the diagnosis and treatment of liver, hemolytic, hematological, and metabolic disorders, including hepatitis and gall bladder block. |
| Special conditions for use | For prescription use only |
| Special instrument requirements | For use on the Roche/Hitachi cobas e clinical chemistry analyzer |
| Candidate device description | cobas e Bilirubin Total Gen.3 reagent provides quantitative measurement of the total bilirubin that is present in serum and plasma of adults and neonates. Reagents are packaged in a cassette with two bottles labeled with their instrument positioning, R1 (Reagent 1) and R2 (Reagent 2). R1 contains detergent, buffer, and stabilizers at pH 1.0. R2 is a 3,5-dichlorophenyl diazonium salt: ≥ 1.35 mmol/L. |
| Predicate device | Roche Diagnostics claims substantial equivalence to the Total Bilirubin reagent on the cobas c 501. The reagent was originally cleared in K981632 on the Boehringer Mannheim/Hitachi 917 analyzer, and later cleared in a Special 510(k) K063543 on COBAS INTEGRA and Roche/Hitachi clinical chemistry analyzers. The application to the cobas c 501 analyzer was cleared on October 3, 2006 in K060373/A001 following the FDA Policy Document "Replacement Reagent and Instrument Family Policy - 12/11/2003". Continued on next page |
5
The following table compares the identical features of the candidate device to Substantial equivalence the predicate device that was cleared in 510(k) K063543. similarities
| Feature | Predicate Device:
Total Bilirubin | Candidate Device:
Bilirubin Total Gen.3 |
|---------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------|
| Intended Use | In vitro test for the quantitative
determination of total bilirubin in
serum and plasma of adults and
neonates on Roche/Hitachi cobas c
systems. | Same |
| Sample Types | Serum and plasma of adults and
neonates | Same |
| Permissible
Anticoagulants | Li-heparin
K2-EDTA | Same |
| Reference Method | Diazo colorimetric method | Same |
| Calibrator | Calibrator for automated systems
(C.f.a.s.) and deionized water as the
zero calibrator
(C.f.a.s. cleared for use with Total
Bilirubin in 510(k) K101456) | Same |
| Calibration Stability | Recalibrate with each lot and as
required following quality control
procedures | Same |
| Reagent Shelf Life
Stability | 2-8 °C until expiration date | Same |
| Calibration Mode | Linear regression | Same |
| Traceability | Standardized against the Doumas
manual reference method | Same |
| Instrument Platform | Roche/Hitachi cobas c 501 | Same |
6
The following table compares the different features of the candidate device to Substantial the predicate device that was cleared in 510(k) K063543. equivalence differences
| Predicate Device: | Candidate Device: | ||
|---|---|---|---|
| Feature | Total Bilirubin | Bilirubin Total Gen.3 | |
| Reagent Composition | RI: | ||
| Sulfamic acid 110 mmol/L, | |||
| Sodium Acetate Buffer 85 | |||
| mmol/L, | |||
| Surfactant, and Solubilizer | R1: | ||
| Detergent, Buffer, and Stabilizers | |||
| at pH 1.0 | |||
| R2: | |||
| Diazonium ion 3 mmol/L, | |||
| HC1 100 mmol/L | R2: | ||
| 3,5-Dichlorophenyl diazonium salt | |||
| ≥ 1.35 mmol/L | |||
| Reagent On-Board | |||
| Stability | on-board in use and refrigerated | ||
| on the analyzers: 5 weeks | on-board in use and refrigerated on | ||
| the analyzers: 6 weeks | |||
| Controls | Precinorm U plus, | ||
| Precipath U plus, | |||
| Precinorm U, | |||
| Precipath U | |||
| (Controls above cleared for use | |||
| with Total Bilirubin in 510(k) | |||
| K042389) | Precinorm U plus, | ||
| Precipath U plus, | |||
| PreciControl ClinChem Multi 14. | |||
| PreciControl ClinChem Multi 24 | |||
| AThese two new controls were | |||
| cleared for use with Total | |||
| Bilirubin with 510(k) K102016. |
7
Substantial equivalence - differences continued
| Feature | Predicate Device:
Total Bilirubin | Candidate Device:
Bilirubin Total Gen.3 |
|--------------------------------|----------------------------------------------------|------------------------------------------------------------------------|
| Measuring Range | 0.10 - 35.1 mg/dL | 0.146 - 35.1 mg/dL |
| Expected Values | Adults and children:
up to 1.0 mg/dL | Adults: up to 1.2 mg/dL |
| | | Children with age ≥ 1 month:
up to 1.0 mg/dL |
| | Neonates
Age of Newborn: Premature | |
| | 24 hours 1.0-6.0 mg/dL | Newborns: Term and near-term
Age of Newborn: |
| | 48 hours 6.0-8.0 mg/dL | |
| | 3-5 days 10.0-15.0 mg/dL | |
| | Age of Newborn: Full Term | |
| | 24 hours 2.0-6.0 mg/dL | |
| | 48 hours 6.0-7.0 mg/dL
3-5 days 10.0-12.0 mg/dL | 24 hours ≥ 8.0 mg/dL
48 hours ≥ 13.0 mg/dL
84 hours ≥ 17.0 mg/dL |
| Lower Limits of
Measurement | LDL = 0.10 mg/dL | LoB = 0.10 mg/dL
LoD = 0.15 mg/dL
LoQ = 0.15 mg/dL |
8
cobas c Bilirubin Total Gen.3 measures total bilirubin by employing the diazo Test principle colorimetric method. Total bilirubin, in the presence of a suitable solubilizing agent, is coupled with a diazonium ion in a strongly acidic medium. The color intensity of the red azo dye formed is directly proportional to the total bilirubin and can be determined photometrically.
Precision was determined according to CLSI EP5-A2. The study included Precision/ reproducibility human sera samples (0.51, 17.7, and 31.8 mg/dL) and two serum-based control samples in two aliquots per run and two runs per day for 21 days.
Here are summaries of the repeatability and intermediate precision data.
| Repeatability Summary | |||||
|---|---|---|---|---|---|
| Specimen | PCCC1* | PCCC2* | Human Serum 1 | Human Serum 2 | Human Serum 3 |
| Total Mean (mg/dL) | 0.90 | 3.09 | 0.51 | 17.7 | 31.8 |
| Within Run Imprecision | |||||
| SD (mg/dL) | 0.02 | 0.02 | 0.01 | 0.10 | 0.14 |
| Within Run Imprecision | |||||
| CV% | 2.1 | 0.6 | 2.9 | 0.6 | 0.4 |
| Min (mg/dL) | 0.85 | 3.03 | 0.46 | 17.36 | 31.41 |
| Max (mg/dL) | 0.94 | 3.15 | 0.55 | 17.95 | 32.43 |
Intermediate Precision
| Specimen | PCCC1* | PCCC2* | Human Serum 1 | Human Serum 2 | Human Serum 3 |
|---|---|---|---|---|---|
| Total Mean (mg/dL) | 0.90 | 3.09 | 0.51 | 17.7 | 31.8 |
| Total Imprecision | |||||
| SD (mg/dL) | 0.02 | 0.03 | 0.02 | 0.14 | 0.18 |
| Total Imprecision | |||||
| CV% | 2.1 | 0.8 | 3.3 | 0.8 | 0.6 |
| Min (mg/dL) | 0.85 | 3.03 | 0.46 | 17.36 | 31.41 |
| Max (mg/dL) | 0.94 | 3.15 | 0.55 | 17.95 | 32.43 |
Values that appear in bold type also appear in the labeling.
*PCCC1 = PreciControl ClinChem Multi 1
*PCCC2 = PreciControl ClinChem Multi 2
9
Linearity was assessed according to CLSI EP6-A with one batch of reagent, Linearity/ assay reportable in one run, and with samples measured in triplicate. Two separate dilution range series differing by sample type (serum and plasma) were prepared with thirteen levels for the plasma series and fourteen levels for the serum series. Lithium-heparin was used to prepare the plasma sample series. The highest concentration samples exceed the desired measuring range. The highest concentration samples were created by taking a human serum/plasma sample pool and spiking it with unconjugated bilirubin.
Measuring Ranges that are Supported by the Linearity Data (mg/dL)
| Plasma | Serum | |
|---|---|---|
| Range tested | 0.12-39.0 | 0.12-38.9 |
| Range found | 0.12-39.0 | 0.12-38.9 |
| Recommended measuring range | 0.15-35.1 | 0.15-35.1 |
The first order (linear) regression is significant for both sample types.
Linear Regression Equation for Serum r2 = 0.999881 y=1.0021x-0.0317
Linear Regression Equation for Plasma r2 = 0.999954 y = 1.0014x - 0.0232
This method has been standardized against the manual test performance using Traceability and stability the Doumas method.
The reagent has been evaluated for transport, shelf-life, and open on-board stability.
10
LoB, LoD, and LoQ studies were performed based upon CLSI EP17-A2. Detection limit
LoB Protocol: One blank sample was tested in n=5 with two analyzers with three reagent batches for six runs per day across three days.
LoD Protocol: Five low-analyte samples were measured in singlicate on two analyzers with three reagent batches for six runs per day across three days.
LoQ Protocol: A low-level sample set of nine was measured in singlicate, using three reagent batches on two analyzers for six runs per day across three days. The LoQ is determined based on precision at 20% CV.
The LoB, LoD, and LoQ claims represent the specifications for each.
LoB claim = 0.10 mg/dL LoD claim = 0.15 mg/dL LoQ claim = 0.15 mg/dL
11
Analvtical specificity interference from endogenous substances
The reagent was evaluated with three endogenous substances, hemoglobin, lipids, and indican for potential interference with the measurement of total bilirubin.
One pool of human serum was spiked with the interferent. A second pool of human serum contained none. The two pools were mixed in different ratios to vield a dilution series with varying concentrations of the interferent.
The endogenous interference data are summarized in the table. Interference was tested at two levels of bilirubin.
| | no interference up to | Claim as it appears in the
labeling. |
|------------------------|-----------------------|-----------------------------------------|
| Lipemia Level 1 | 1196 L index | No significant interference up |
| Lipemia Level 2 | 1217 L index | to an L index of 1000. |
| Hemolysis HbA Level 1 | 946 H index | No significant interference up |
| Hemolysis HbA Level 2 | 951 H index | to an H index of 800. |
| *Hemolysis HbF Level 1 | 1053 H index | No significant interference up |
| *Hemolysis HbF Level 2 | 1047 H index | to an H index of 1000. |
| Indican Level 1 | 3.75 mg/dL | No significant interference |
| Indican Level 2 | 3.75 mg/dL | from indican up to 3 mg/dL. |
*HbF was tested for hemolysis interference in neonates.
All data passed the following acceptance criteria:
Lipemia: ≤± 0.10 mg/dL for samples ≤ 1 mg/dL or ≤± 10% for samples > 1 mg/dL
Hemolysis HbA: ≤±0.20 mg/dL for samples ≤ 2 mg/dL or ≤± 10% for samples > 2 mg/dL.
Hemolysis in neonates - HbF: ≤± 0.10 mg/dL for samples ≤ 1 mg/dL or ≤ ± 10% for samples > 1 mg/dL
Indican: ≤± 0.10 mg/dL for samples ≤ 1 mg/dL or ≤± 10% for samples > 1 mg/dL
12
Fifteen commonly used drugs were examined for potential interference on Analytical specificity measurement with cobas c Bilirubin Total Gen.3 reagent. interference from common Drug interference testing was performed with serum sample pools at two drugs target concentrations of total bilirubin, one at a low concentration of ~ 1.0 mg/dL and the second one at a high concentration of ~ 14.0 mg/dL.
Total bilirubin concentration in all aliquots is measured in triplicate. The mean value among the triplicates for each aliquot is determined. From the mean values, the percent recovery to the initial value (no drug in sample) is calculated.
| | Drug | Highest Concentration Shown
Not to Interfere with BILT3
(drug concentrations in mg/L) |
|----|----------------------|---------------------------------------------------------------------------------------------|
| 1 | Acetylcystein | 150 |
| 2 | Ampicillin - Na | 1000 |
| 3 | Ascorbic acid | 300 |
| 4 | Phenylbutazone | 400 |
| 5 | Cyclosporine A | 5 |
| 6 | Cefoxitin | 2500 |
| 7 | Levodopa | 20 |
| 8 | Methyldopa + 1.5 | 20 |
| 9 | Metronidazole | 200 |
| 10 | Doxycyclin | 50 |
| 11 | Acetylsalycilic acid | 1000 |
| 12 | Rifampicin | 60 |
| 13 | Acetaminophen | 200 |
| 14 | Ibubrofen | 500 |
| 15 | Theophylline | 100 |
The table below summarizes the common drug interferences data:
All data passed the following acceptance criteria:
Difference in recovery to the reference sample: ≤± 10%
13
| Adult method
comparison
with predicate
device | Total bilirubin values for n=131 human sera adult samples were obtained
using the candidate reagent (y-axis) to the predicate reagent (x-axis) on the
Roche/Hitachi cobas c 501 analyzer. Candidate sample concentrations
ranged from 0.18 to 30.38 mg/dL, and they were tested in singlicate. The
values were regressed using the Passing/Bablok model to produce the
following equation. |
|--------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | $y = 0.959x + 0.091 mg/dL$ |
| | $r = 0.9997$ |
14
Lithium-heparin and K2-EDTA are permissible anticoagulants for use with Matrix this reagent because they do not interfere with recovery of total bilirubin. In comparison an internal study, 35 tubes were collected per anticoagulant. Plasma results were compared to serum results and percent recovery was determined. In terms of % recovery. All data passed the following criteria: For sample concentrations ≤ 0.99 mg/dL, the deviation must be ≤ ± 0.10
mg/dL. For sample concentrations > 0.99 mg/dL, the deviation must be ≤± 10%.
| anticoagulants | Sample concentration
range tested (mg/dL) | Claimed Measuring
Range (mg/dL) |
|---------------------|----------------------------------------------|------------------------------------|
| Li-Heparin (full) | 0.35 - 34.52 | |
| Li-Heparin (half) | 0.84 - 31.65 | 0.15 - 35.1 |
| K2-EDTA (full) | 0.36 - 34.46 | |
| K2-EDTA (half) | 0.80 - 31.18 | |
| Gel Separation Tube | 0.36 - 34.40 | |
In addition, method comparisons with plasma vs serum were calculated with the following results:
| Serum vs. Li-heparin > P/B: y = 1.000x + 0.000, r = 0.9998 | |
|---|---|
| Serum vs. K2-EDTA |
15
| Expected
values/
| reference range | Adults¹ | up to 1.2 mg/dL |
|---|---|---|
| Children with age ≥ 1 month¹ | up to 1.0 mg/dL | |
| Newborns: Term and near-term² | ||
| Age of Newborn: | ||
| 24 hours | ≥ 8.0 mg/dL | |
| 48 hours | ≥ 13.0 mg/dL | |
| 84 hours | ≥ 17.0 mg/dL | |
| 1. Thomas L. Labor und Diagnose. Indikation und Bewertung von | ||
| Laborbefunden fur die Medizinische Diagnostik. 7th ed. TH-Books | ||
| Verlagsgesellschaft 2007:259-273. | ||
| 2. Subcommittee on Hyperbilirubinemia. Management of | ||
| Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of | ||
| Gestation. Pediatrics 2004; 114: 297-316. |
1