(59 days)
The Total Bilirubin2 assay is used for the quantitation of total bilirubin in human serum or plasma, of adults and neonates, on the ARCHITECT c System.
Measurement of total bilirubin, an organic compound formed during the normal destruction of red blood cells, is used in the diagnosis and treatment of liver, hematological, and metabolic disorders, including hepatitis and disorders of the biliary tract. In newborn infants, the Total Bilirubin2 assay is intended to measure the levels of total bilirubin (conjugated and unconjugated) in serum or plasma to aid in the diagnosis and management of neonatal jaundice and hemolytic disease of the newborn.
The Total Bilirubin2 assay (subject device) is an automated clinical chemistry assay for the quantitation of total bilirubin in human serum or plasma, of adults and neonates, on the ARCHITECT c System. Total (conjugated and unconjugated) bilirubin couples with a diazo reagent in the presence of a surfactant to form azobilirubin. The diazo reaction is accelerated by the addition of surfactant as a solubilizing agent. The increase in absorbance at 548 nm due to azobilirubin is directly proportional to the total bilirubin concentration. The methodology is Diazonium salt.
The provided text describes a 510(k) premarket notification for a medical device called "Total Bilirubin2", an in vitro diagnostic assay. This type of submission focuses on demonstrating substantial equivalence to a legally marketed predicate device, rather than proving clinical effectiveness through the extensive studies typically associated with AI/ML diagnostic tools. Therefore, the questions related to AI/ML specific criteria (like MRMC studies, number of experts for ground truth, sample size for training sets, etc.) are not applicable in this context.
The document primarily details the analytical performance of the Total Bilirubin2 assay.
Here's an analysis based on the information provided, adhering to the request:
Acceptance Criteria and Reported Device Performance
The acceptance criteria for this in vitro diagnostic device are typically defined by ranges of acceptable analytical performance, following established CLSI (Clinical and Laboratory Standards Institute) guidelines. The reported device performance is compared against these internal acceptance criteria.
| Performance Metric | Acceptance Criteria (Implicit from CLSI Guidelines/Industry Standards) | Reported Device Performance (as stated) |
|---|---|---|
| Reportable Interval (Range) | Established analytical measuring interval, extended measuring interval, and reportable interval. | Analytical Measuring Interval (AMI): 0.1 – 25.0 mg/dL Extended Measuring Interval (EMI): 25.0 – 125.0 mg/dL Reportable Interval: 0.1 – 125.0 mg/dL |
| Within-Laboratory Precision (SD/CV%) | Specific maximum acceptable SD and %CV for different concentrations, as per CLSI EP05-A3 guidelines. | Control Level 1 (1.1 mg/dL): SD: 0.04 (Range 0.02-0.04), %CV: 3.4 (Range 1.8-3.4) Control Level 2 (4.2 mg/dL): SD: 0.09 (Range 0.09-0.10), %CV: 2.1 (Range 2.0-2.2) Panel A (0.3 mg/dL): SD: 0.00 (Range 0.00-0.03), %CV: 0.0 (Range 0.0-9.2) Panel B (13.3 mg/dL): SD: 0.11 (Range 0.09-0.12), %CV: 0.8 (Range 0.7-0.9) Panel C (22.3 mg/dL): SD: 0.16 (Range 0.16-0.18), %CV: 0.7 (Range 0.7-0.8) |
| System Reproducibility (SD/CV%) | Specific maximum acceptable SD and %CV for different concentrations, as per CLSI EP05-A3 guidelines. | Control Level 1 (1.1 mg/dL): SD: 0.02, %CV: 2.2 Control Level 2 (4.5 mg/dL): SD: 0.16, %CV: 3.5 Panel B (13.4 mg/dL): SD: 0.57, %CV: 4.3 Panel C (22.4 mg/dL): SD: 1.12, %CV: 5.0 |
| Accuracy (Bias) | Bias within an acceptable range, relative to a reference method (Doumas). | Bias ranged from -0.1% to 3.7%. |
| Lower Limits of Measurement | Defined LoB, LoD, and LoQ based on CLSI EP17-A2 guidelines. | LoB: 0.02 mg/dL LoD: 0.04 mg/dL LoQ: 0.07 mg/dL |
| Linearity | Linearity across the specified analytical measuring interval. | Linear across the analytical measuring interval of 0.1 to 25.0 mg/dL. |
| Interference (Endogenous) | Interference within ± 10% for specified substances at given concentrations. | Hemoglobin (1000 mg/dL), Total protein (15 g/dL), Triglycerides (1500 mg/dL): No significant interference (within ± 10%). Indican (1 mg/dL): No significant interference. Indican (2 mg/dL): 17% interference (beyond ±10%). |
| Interference (Exogenous) | Interference within ± 10% for specified substances at given concentrations. | Variety of common drugs tested; no significant interference for most. Indocyanine green (10 mg/L): 9% interference. |
| Method Comparison (Correlation) | High correlation coefficient and acceptable slope/intercept when compared to predicate device. | Serum: Correlation Coefficient: 1.00, Intercept: -0.03, Slope: 1.03 (Range 0.1–22.5 mg/dL) Neonatal serum: Correlation Coefficient: 1.00, Intercept: 0.00, Slope: 1.00 (Range 0.2–22.8 mg/dL) |
| Tube Type Suitability | Acceptable performance across specified tube types. | Serum tubes, Serum separator tubes, Dipotassium EDTA tubes, Lithium heparin tubes, Lithium heparin separator tubes, Sodium heparin tubes were acceptable. |
| Dilution Verification (% Recovery & %CV) | % recovery within 100% ± 10%; imprecision ≤ 7 %CV for automated dilution, ≤ 8 %CV for manual dilution. | Automated Dilution: 96.3% to 104.4% recovery, 1.6% to 2.5% CV. Manual Dilution: 95.0% to 106.7% recovery, 2.2% to 4.9% CV. |
Study Details:
-
Sample size used for the test set and the data provenance:
- Precision (Within-Laboratory): 80 replicates for each control/panel (on a representative combination out of 3 multi-lot/instrument combinations).
- Reproducibility (System): 84 replicates for each control/panel.
- Lower Limits of Measurement: ≥ 60 replicates for LoB and LoD for each of 3 lots on 2 instruments.
- Interfering Substances: Not explicitly stated, but "Each substance was tested at 2 levels of the analyte."
- Method Comparison:
- Serum: 167 samples
- Neonatal serum: 163 samples
- Tube Type: Samples collected from a minimum of 40 donors.
- Dilution Verification: 5 samples prepared with varying concentrations.
- Data Provenance: Not explicitly stated regarding country of origin or whether retrospective/prospective. However, given the nature of in vitro diagnostic analytical studies, samples are typically acquired prospectively or from biobanks for specific analytical testing purposes.
-
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- For in vitro diagnostic devices like this bilirubin assay, "ground truth" is established by reference methods or highly characterized calibrators/control materials, not by expert human readers. The accuracy study, for example, compares results to material standardized to the Doumas Total Bilirubin reference method, which represents the "ground truth" for bilirubin measurement. Therefore, expert readers/adjudicators as typically seen in imaging AI studies are not applicable here.
-
Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- Not applicable. This is an in vitro diagnostic assay, and its performance is evaluated against analytical measurements, not human interpretations requiring adjudication.
-
If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- Not applicable. This device is an in vitro diagnostic test, not an AI/ML-driven imaging or diagnostic algorithm designed to assist human readers.
-
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Not applicable. This is an assay performed on an automated system, providing a quantitative result. Its "performance" is inherently "standalone" in generating the numerical value, but it's not an AI algorithm in the sense of image interpretation or complex diagnostic inference.
-
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- For analytical performance studies, the "ground truth" for bilirubin concentration is established by reference methods (e.g., the Doumas method for accuracy) or by using certified reference materials and calibrators with known concentrations. This is the gold standard for quantitative in vitro diagnostic measurements.
-
The sample size for the training set:
- Not applicable. This is not an AI/ML device that requires a "training set" in the computational sense. The device's performance is a function of its reagents, instrument, and established methodology, not a learned algorithm.
-
How the ground truth for the training set was established:
- Not applicable. See above.
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December 29, 2022
Abbott Ireland Diagnostics Division Magdalena Suszko Associate Director Regulatory Affairs Lisnarnuck, Longford Co. Longford, Ireland
Re: K223324
Trade/Device Name: Total Bilirubin2 Regulation Number: 21 CFR 862.1110 Regulation Name: Bilirubin (total or direct) test system Regulatory Class: Class II Product Code: CIG, MQM Dated: October 27, 2022 Received: October 31, 2022
Dear Magdalena Suszko:
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.
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
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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 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/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); 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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
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/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). 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 (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Marianela Perez-torres -S
Marianela Perez-Torres, Ph.D. Acting Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K223324
Device Name Total Bilirubin2
Indications for Use (Describe)
The Total Bilirubin2 assay is used for the quantitation of total bilirubin in human serum or plasma, of adults and neonates, on the ARCHITECT c System.
Measurement of total bilirubin, an organic compound formed during the normal destruction of red blood cells, is used in the diagnosis and treatment of liver, hematological, and metabolic disorders, including hepatitis and disorders of the biliary tract. In newborn infants, the Total Bilirubin2 assay is intended to measure the levels of total bilirubin (conjugated and unconjugated) in serum or plasma to aid in the diagnosis and management of neonatal jaundice and hemolytic disease of the newborn.
| Type of Use (Select one or both, as applicable) |
|---|
| ------------------------------------------------- |
X Prescription Use (Part 21 CFR 801 Subpart D)
| Over-The-Counter Use (21 CFR 801 Subpart C)
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510(k) Summary (Summary of Safety and Effectiveness)
This summary of the 510(k) safety and effectiveness information is being submitted in accordance with the requirements of Safe Medical Device Amendments (SMDA) of 1990 and 21 CFR §807.92.
I. 510(k) Number
II. Applicant Name
Abbott Ireland Diagnostics Division Lisnamuck, Longford Co. Longford Ireland
Primary contact person for all communications:
Magdalena Suszko, Associate Director, Regulatory Affairs Abbott Laboratories, Diagnostics Division Phone (224) 667-9025 Fax (224) 667-4836
Secondary contact person for all communications:
Elizabeth Molina Campos, Project Manager, Regulatory Affairs Abbott Laboratories, Diagnostics Division Phone (224) 667-0037 Fax (224) 667-4836
Date Summary Prepared: December 20, 2022
III. Device Name
Trade Name: Total Bilirubin2
Device Classification: Class II Classification Name: Bilirubin (total or direct) test system. Governing Regulation Number: 21 CFR §862.1110 Product Code: CIG
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Device Classification: Class I, reserved Classification Name: Bilirubin (total and unbound) in the neonate test system Governing Regulation Number: 21 CFR §862.1113 Product Code: MQM
IV. Predicate Device
ARCHITECT Total Bilirubin (K121985)
V. Description of Device
A. Principles of the Procedure
Total (conjugated and unconjugated) bilirubin couples with a diazo reagent in the presence of a surfactant to form azobilirubin. The diazo reaction is accelerated by the addition of surfactant as a solubilizing agent. The increase in absorbance at 548 nm due to azobilirubin is directly proportional to the total bilirubin concentration.
Methodology: Diazonium salt
B. Reagents
The configurations of the Total Bilirubin2 reagent kits are described below.
| List Number | ||
|---|---|---|
| 04T0920 | 04T0930 | |
| Tests per cartridge set | 225 | 450 |
| Number of cartridge sets per kit | 4 | 8 |
| Tests per kit | 900 | 3600 |
| Reagent 1 (R1) | 44.5 mL | 85.9 mL |
| Reagent 2 (R2) | 14.5 mL | 26.7 mL |
Active ingredient: Brij L23 (233.333 mL/L). R1
R2 Active ingredients: 2,4-dichlorobenzenediazonium 1,5naphthalenedisulfonate hydrate (1845.000 mg/L) and Brij L23 (100.000 mL/L).
VI. Intended Use of the Device
The Total Bilirubin2 assay is used for the quantitation of total bilirubin in human serum or plasma, of adults and neonates, on the ARCHITECT c System.
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Measurement of total 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 disorders of the biliary tract. In newborn infants, the Total Bilirubin2 assay is intended to measure the levels of total bilirubin (conjugated and unconjugated)in serum or plasma to aid in the diagnosis and management of neonatal jaundice and hemolytic disease of the newborn.
VII. Comparison of Technological Characteristics
The Total Bilirubin2 assay (subject device) is an automated clinical chemistry assay for the quantitation of total bilirubin in human serum or plasma, of adults and neonates, on the ARCHITECT c System.
The similarities and differences between the subject device and the predicate device are presented in the following table.
| Similarities and Differences Between | ||
|---|---|---|
| Device & Predicate Device: | ||
| Device:Total Bilirubin2 | Predicate Device:ARCHITECT Total Bilirubin(List No. 6L45) (K121985) | |
| General Device Similarities | ||
| Platform | ARCHITECT c8000 System | Same |
| Similarities and Differences Between | ||
| Device & Predicate Device: | ||
| Device:Total Bilirubin2 | Predicate Device:ARCHITECT Total Bilirubin(List No. 6L45) (K121985) | |
| Intended Use andIndications forUse | The Total Bilirubin2 assay is used for the quantitation of total bilirubin in human serum orplasma, of adults and neonates,on the ARCHITECT c System.Measurement of total bilirubin, anorganic compound formed during thenormal and abnormal destruction of redblood cells, is used in the diagnosis andtreatment of liver, hemolytic,hematological, and metabolic disorders,including hepatitis and disorders of thebiliary tract. In newborn infants, the TotalBilirubin2 assay is intended to measurethe levels of bilirubin in serum or plasmato aid in the diagnosis and managementof neonatal jaundice and hemolyticdisease of the newborn. | The ARCHITECT Total Bilirubinassay is used for the quantitation oftotal bilirubin in human serum orplasma on the ARCHITECT c8000system. Measurement of totalbilirubin, an organic compoundformed during the normal andabnormal destruction of red bloodcells, is used in the diagnosis andtreatment of liver, hemolytichematological and metabolicdisorders, including hepatitis andgall bladder block.A bilirubin (total and unbound) inthe neonate test system is a deviceintended to measure the levels ofbilirubin (total and unbound) in theblood (serum) of newborn infantsto aid in indicating the risk ofbilirubin encephalopathy(kernicterus). |
| Methodology | Diazonium salt | Same |
| Specimen Type | Human serum or plasma | Same |
| Assay Principle /Principle ofProcedure | Total (conjugated and unconjugated)bilirubin couples with a diazo reagent inthe presence of a surfactant to formazobilirubin. The diazo reaction isaccelerated by the addition of surfactantas a solubilizing agent. The increase inabsorbance at 548 nm due to azobilirubinis directly proportional to the totalbilirubin concentration. | Same |
| Standardization | Doumas method | Same |
| Use of Calibrators | Yes | Same |
| Use of Controls | Yes | Same |
| Similarities and Differences Between | ||
| Device & Predicate Device: | ||
| Device:Total Bilirubin2 | Predicate Device:ARCHITECT Total Bilirubin(List No. 6L45) (K121985) | |
| Assay Range | Analytical Measuring Interval:0.1–25.0 mg/dLExtended Measuring Interval:25.0–125.0 mg/dLReportable Interval:0.1–125.0 mg/dL | Same |
| Tube Types | Serum:- Serum tubes- Serum separator tubesPlasma:- Dipotassium EDTA tubes- Lithium heparin tubes- Lithium heparin separator tubes- Sodium heparin tubes | Same |
| General Device Differences | ||
| Lower Limits ofMeasurement | Limit of Blank: 0.02 mg/dLLimit of Detection: 0.04 mg/dLLimit of Quantitation: 0.07 mg/dL | Limit of Blank: 0.01 mg/dLLimit of Detection: 0.05 mg/dLLimit of Quantitation: 0.07 mg/dL |
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VIII. Summary of Nonclinical Performance
All performance characteristics were obtained using the ARCHITECT c8000 System.
A. Reportable Interval
Based on the limit of detection (LoD), limit of quantitation (LoQ), precision, and linearity, the ranges over which results can be reported are provided below according to the definitions from CLSI EP34, 1st ed. *
| mg/dL | |
|---|---|
| Analytical Measuring Interval (AMI)a | 0.1-25.0 |
| Extended Measuring Interval (EMI)b | 25.0-125.0 |
| Reportable Intervalc | 0.1-125.0 |
ª AMI: The AMI is determined by the range of values in mg/dL that demonstrated acceptable performance for linearity, imprecision, and bias. NOTE: The observed LoQ has been rounded up to the number of decimal places defined in the assay file.
b EMI: The EMI extends from the upper limit of quantitation (ULoQ) to the ULoQ × sample dilution.
^ The reportable interval extends from the LoD (rounded up to the number of decimal places defined in the assay file) to the upper limit of the EMI.
NOTE: The Low Linearity value of the assay file corresponds to the lower limit of the AMI. Samples with a total bilirubin value below 0.1 mg/dL are reported as "<0.1 mg/dL".
Clinical and Laboratory Standards Institute (CLS). Establishing and Verifying an Extended Measuring Interval Through Specimen Dilution and Spiking. 1st ed. CLSI Document EP34. Wayne, PA: CLSI; 2018.
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B. Within-Laboratory Precision
Within-Laboratory Precision
A study was performed based on guidance from CLSI EP05-A3. * Testing was conducted using 3 lots of the Total Bilirubin2 reagents, 3 lots of the Consolidated Chemistry Calibrator, 1 lot of commercially available controls, and 3 instruments. Two controls and 3 human serum panels were tested in a minimum of 2 replicates, twice per day for 20 days on 3 reagent lot/calibrator lot/instrument combinations, where a unique reagent lot and a unique calibrator lot are paired with 1 instrument. The performance from a representative combination is shown in the following table.
| Within-Run(Repeatability) | Within-Laboratorya | |||||
|---|---|---|---|---|---|---|
| Sample | n | Mean(mg/dL) | SD | %CV | SD(Rangeb) | %CV(Rangeb) |
| Control Level 1 | 80 | 1.1 | 0.02 | 1.9 | 0.04(0.02-0.04) | 3.4(1.8-3.4) |
| Control Level 2 | 80 | 4.2 | 0.04 | 0.9 | 0.09(0.09-0.10) | 2.1(2.0-2.2) |
| Panel A | 80 | 0.3 | 0.00 | 0.0 | 0.00(0.00-0.03) | 0.0(0.0-9.2) |
| Panel B | 80 | 13.3 | 0.09 | 0.7 | 0.11(0.09-0.12) | 0.8(0.7-0.9) |
| Panel C | 80 | 22.3 | 0.15 | 0.7 | 0.16(0.16-0.18) | 0.7(0.7-0.8) |
a Includes within-run, between-run, and between-day variability.
b Minimum and maximum SD or %CV across the 3 reagent lot/calibrator lot/instrument combinations.
T Clinical and Laboratory Standards Institute (CLSI). Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline-Third Edition. CLSI Document EP05-A3. Wayne, PA: CLSI; 2014.
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System Reproducibility
A study was performed based on guidance from CLSI EP05-A3.+ Testing was conducted using 1 lot of the Total Bilirubin2 reagents, 1 lot of the Consolidated Chemistry Calibrator, 1 lot of commercially available controls, and 3 instruments. Each instrument was operated by a different technician. Two controls and 2 human serum panels were tested in a minimum of 3 replicates at 2 separate times per day on 5 different days on 2 instruments and on 4 different days on 1 instrument.
| Mean | Repeatability | Within-Laboratorya | Reproducibilityb | |||||
|---|---|---|---|---|---|---|---|---|
| Sample | n | (mg/dL) | SD | %CV | SD | %CV | SD | %CV |
| ControlLevel 1 | 84 | 1.1 | 0.02 | 1.6 | 0.02 | 2.1 | 0.02 | 2.2 |
| ControlLevel 2 | 84 | 4.5 | 0.03 | 0.6 | 0.06 | 1.5 | 0.16 | 3.5 |
| Panel B | 84 | 13.4 | 0.08 | 0.6 | 0.10 | 0.7 | 0.57 | 4.3 |
| Panel C | 84 | 22.4 | 0.13 | 0.6 | 0.17 | 0.7 | 1.12 | 5.0 |
ª Includes within-run, between-run, and between-day variability.
b Includes within-run, between-run, between-day, and between-instrument variability.
C. Accuracy
A study was performed to estimate the bias of the Total Bilirubin2 assay relative to material standardized to the Doumas Total Bilirubin reference method. Testing was conducted using 2 concentrations of bilirubin from human serum across 3 lots of the Total Bilirubin2 reagents, 2 lots of the Consolidated Chemistry Calibrator, and 1 instrument. The bias ranged from -0.1% to 3.7%.
+ Clinical and Laboratory Standards Institute (CLSI). Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline-Third Edition. CLSI Document EP05-A3. Wayne, PA: CLSI; 2014.
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D. Lower Limits of Measurement
A study was performed based on guidance from CLSI EP17-A2.8 Testing was conducted using 3 lots of the Total Bilirubin2 reagents on each of 2 instruments over a minimum of 3 days. The maximum observed limit of blank (LoB), limit of detection (LoD), and limit of quantitation (LoQ) values are summarized below.
| mg/dL | |
|---|---|
| LoBa | 0.02 |
| LoDb | 0.04 |
| LoQc | 0.07 |
4 The LoB represents the 95th percentile from n ≥ 60 replicates of zero-analyte samples.
b The LoD represents the lowest concentration at which the analyte can be detected with 95% probability based on n ≥ 60 replicates of low-analyte level samples.
& The LoQ is defined as the lowest concentration at which a maximum allowable precision of 20% CV was met and was determined from n ≥ 60 replicates of low-analyte level samples.
E. Linearity
A study was performed based on guidance from CLSI EP06-A.** This assay is linear across the analytical measuring interval of 0.1 to 25.0 mg/dL.
§ Clinical and Laboratory Standards Institute (CLSI). Evaluation of Detection Capability for Clinical Laboratory Measurent Procedures; Approved Guideline-Second Edition. CLSI Document EP17-A2. Wayne, PA: CLSI; 2012.
** Clinical and Laboratory Standards Institute (CLSI). Evaluetitative Measurement Procedures: A Staristical Approach; Approved Guideline. CLSI Document EP06-A. Wayne, PA: CLSI; 2003.
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F. Potentially Interfering Endogenous and Exogenous Substances
Potentially Interfering Endogenous Substances
A study was performed based on guidance from CLSI EP07, 3rd ed. Each substance was tested at 2 levels of the analyte (approximately 2 mg/dL and 15 mg/dL). No significant interference (interference within ± 10%) was observed at the following concentrations.
| No Significant Interference (Interference within ± 10%) | |
|---|---|
| Potentially Interfering Substance | Interferent Level |
| Hemoglobin | 1000 mg/dL |
| Indican | 1 mg/dL |
| Total protein | 15 g/dL |
| Triglycerides | 1500 mg/dL |
Interference beyond ± 10% (based on 95% Confidence Intervals [CI]) was
observed at the concentration shown below for the following substance.
| Interference beyond ± 10% (based on 95% Confidence Interval [CI]) | ||||
|---|---|---|---|---|
| Potentially InterferingSubstance | Interferent Level | Analyte Level | % Interference(95% CI) | |
| Indican | 2 mg/dL | 2 mg/dL | 17%(15%, 19%) |
Potentially Interfering Exogenous Substances
A study was performed based on guidance from CLSI EP07, 3rd ed. Each substance was tested at 2 levels of the analyte (approximately 2 mg/dL and 15 mg/dL).
Clinical and Laboratory Standards Institute (CLS). Interference Testing in Clinical Chemistry. 3rd ed. CLSI Guideline EP07. Wayne, PA: CLSI; 2018.
Clinical and Laboratory Standards Institute (CLS). Interference Testing in Clinical Chemistry. 3rd ed. CLSI Guideline EP07. Wayne, PA: CLSI; 2018.
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No significant interference (interference within ± 10%) was observed at the following concentrations.
| No Significant Interference (Interference within ± 10%) | |
|---|---|
| Potentially Interfering Substance | Interferent Level |
| 4-Hydroxypropranolol glucuronide | 0.2 mg/dL |
| Acetaminophen | 160 mg/L |
| Acetylcysteine | 150 mg/L |
| Acetylsalicylic acid | 30 mg/L |
| Ampicillin-Na | 80 mg/L |
| Ascorbic acid | 60 mg/L |
| Biotin | 4250 ng/mL |
| Ca-dobesilate | 60 mg/L |
| Cefoxitin | 6600 mg/L |
| Cyanokit (hydroxocobalamin) | 2259 mg/L |
| Cyclosporine | 2 mg/L |
| Doxycycline | 20 mg/L |
| Eltrombopag | 300 mg/L |
| Ibuprofen | 220 mg/L |
| Indocyanine green | 5 mg/L |
| Iron dextran | 60 mg/L |
| Levodopa | 8 mg/L |
| Methyldopa | 25 mg/L |
| Metronidazole | 130 mg/L |
| Oxytetracycline | 12 mg/L |
| Phenylbutazone | 330 mg/L |
| Propranolol | 0.1 mg/dL |
| No Significant Interference (Interference within ± 10%) | |
| Potentially Interfering Substance | Interferent Level |
| Rifampicin | 50 mg/L |
| Sodium heparin | 4 U/mL |
| Theophylline (1,3-dimethylxanthine) | 60 mg/L |
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Interference beyond ± 10% (based on 95% Confidence Intervals [CI]) was
observed at the concentrations shown below for the following substance.
| Interference beyond ± 10% (based on 95% Confidence Interval [CI]) | |||||||
|---|---|---|---|---|---|---|---|
| Potentially InterferingSubstance | Interferent Level | Analyte Level | % Interference(95% CI) | ||||
| Indocyanine green | 10 mg/L | 2 mg/dL | 9%(8%, 11%) |
G. Method Comparison
A study was performed based on guidance from CLSI EP09c, 3rd ed.t* using the Passing-Bablok regression method.
| Total Bilirubin2 vs Total Bilirubin on the ARCHITECT c System | ||||||
|---|---|---|---|---|---|---|
| n | Units | Correlation Coefficient | Intercept | Slope | Concentration Range | |
| Serum | 167 | mg/dL | 1.00 | -0.03 | 1.03 | 0.1–22.5 |
| Neonatal serum | 163 | mg/dL | 1.00 | 0.00 | 1.00 | 0.2–22.8 |
** Clinical and Laboratory Standards Institute (CLSI). Measurement Procedure Comparison Using Patient Samples. 3rd ed. CLSI Guideline EP09c. Wayne, PA: CLSI; 2018.
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H. Tube Type
A study was performed to evaluate the suitability of specific blood collection tube types for use with the Total Bilirubin2 assay. Samples were collected from a minimum of 40 donors and evaluated across tube types. The following blood collection tube types were determined to be acceptable for use with the Total Bilirubin2 assay:
Serum
- . Serum tubes
- . Serum separator tubes
Plasma
- . Dipotassium EDTA tubes
- . Lithium heparin tubes
- . Lithium heparin separator tubes
- . Sodium heparin tubes
I. Dilution Verification
A study was performed based on guidance from CLSI EP34 1st ed. * to evaluate the performance of the automated dilution protocol and manual dilution procedure of the Total Bilirubin2 assay (LN 04T09) on the ARCHITECT c8000 instrument.
Five samples were prepared to have total bilirubin concentrations within the extended measuring interval (EMI) of the Total Bilirubin2 assay by spiking total bilirubin stock into a serum pool to the target concentration values of 30.0 mg/dL, 55.0 mg/dL, 70.0 mg/dL, 90.0 mg/dL, and 110.0 mg/dL.
The performance of the automated dilution protocol (1:5) and manual dilution procedure (1:5) was considered acceptable if, for samples within the EMI, the dilution recovery was within or equal to 100% ± 10% when comparing auto-diluted or manually
Clinical and Laboratory Standards Institute (CLS). Establishing and Verifying an Extended Measuring Interval Through Specimen Dilution and Spiking. 1st ed. CLSI Guideline EP34. Wayne, PA: CLSI; 2018.
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diluted samples to target or assigned concentrations and the imprecision was ≤ 7 %CV for the automated dilution protocol and ≤ 8 %CV for manual dilution procedure.
The % recovery results of 96.3% to 104.4% for the automated dilution, and 95.0% to 106.7% for the manual dilution, demonstrated acceptable performance.
The imprecision results of 1.6% to 2.5% for the automated dilution, and 2.2% to 4.9% for the manual dilution, demonstrated imprecision ≤ 7 %CV for the automated dilution protocol and ≤ 8 %CV for manual dilution procedure.
IX. Summary of Clinical Performance
This section does not apply.
X. Conclusion Drawn from Nonclinical Laboratory Studies
The results presented in this 510(k) premarket notification demonstrate that the performance of the subject device, Total Bilirubin2 (List No. 04T09), is substantially equivalent to the predicate device, Total Bilirubin (List No. 6L45, K121985).
The similarities and differences between the subject device and predicate device are presented in Section 5-VII.
There is no known potential adverse effect to the operator when using this in vitro device according to the Total Bilirubin2 reagent package insert instructions.
§ 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.