(34 days)
The Total Bilirubin assay is used for the quantitation of total bilirubin in human serum or plasma of adults and neonates on the ARCHITECT c8000 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 gall bladder block. A bilirubin (total and unbound) in the neonate test system is a device intended to measure the levels of bilirubin (total and unbound) in the blood (serum) of newborn infants to aid in indicating the risk of bilirubin encephalopathy (kernicterus).
The Total Bilirubin reagent kit contains Reagent 1 and Reagent 2. Reagent 1 contains Surfactants and HCl. Reagent 2 contains 2, 4-dichloroaniline, HCl, Sodium nitrite, and Surfactant. The principles of the procedure involve total (conjugated and unconjugated) bilirubin coupling with a diazo reagent in the presence of a surfactant to form azobilirubin. The increase in absorbance at 548 nm due to azobilirubin is directly proportional to the total bilirubin concentration. The detection of the analyte is end-point colorimetric.
Here's an analysis of the provided text regarding the acceptance criteria and study for the Total Bilirubin device:
1. Table of Acceptance Criteria and Reported Device Performance:
The document doesn't explicitly state "acceptance criteria" for each test in a formal table, but rather describes the methodology and then reports the results. I will infer the acceptance criteria from the statements provided about what is considered acceptable or how performance supports the claims.
| Performance Characteristic | Acceptance Criteria (Inferred from text) | Reported Device Performance |
|---|---|---|
| Limit of Quantitation (LOQ) | Support the lower end of the measuring interval (0.3 mg/dL). | The LoQ of the Total Bilirubin assay is 0.174 mg/dL. The LoQ supports the lower end of the measuring interval of 0.3 mg/dL. LoD is 0.174 mg/dL and LoB is 0.102 mg/dL. |
| Linearity | Demonstrate linearity across the measuring interval of 0.3 to 25.0 mg/dL. | The Total Bilirubin assay was demonstrated to be linear across the measuring interval of 0.3 to 25.0 mg/dL. |
| Precision (Within-Laboratory/Total) | Not explicitly stated as a numerical criterion in %CV or SD, but the study was conducted according to CLSI EP5-A2, implying adherence to industry-standard precision expectations. | |
| Sample 1 (0.87 mg/dL): Within Run SD 0.010 mg/dL (1.2%CV), Total SD 0.018 mg/dL (2.1%CV). | ||
| Sample 2 (4.53 mg/dL): Within Run SD 0.034 mg/dL (0.8%CV), Total SD 0.057 mg/dL (1.3%CV). | ||
| Sample 3 (6.42 mg/dL): Within Run SD 0.041 mg/dL (0.6%CV), Total SD 0.066 mg/dL (1.0%CV). | ||
| Sample 4 (16.85 mg/dL): Within Run SD 0.115 mg/dL (0.7%CV), Total SD 0.204 mg/dL (1.2%CV). | ||
| Interference | Bias of > 10%, or > 0.2 mg/dL (> 3.4 umol/L) for bilirubin concentrations ≤ 2.0 mg/dL is considered significant interference. | Hemoglobin (2000 mg/dL): At 1.0 mg/dL, -9.8% bias. At 13.4 mg/dL, -3.0% bias. Intralipid (1000 mg/dL): At 1.0 mg/dL, -0.6% bias. At 13.4 mg/dL, -0.6% bias. Indican (0.125 mmol/L): At 0.9 mg/dL, 26.7% bias. At 14.7 mg/dL, 3.2% bias. Conclusion: Indican, at concentrations > 0.125 mmol/L, interferes with the assay in samples with bilirubin levels at 1.2 mg/dL. |
| Method Comparison (Predicate) | Correlation coefficient and regression line (slope close to 1, intercept close to 0) indicating substantial equivalence to the predicate. | Adult Population (N=118): Slope 0.99, Intercept -0.09, Correlation Coefficient 0.9994. Range: 0.3 to 24.8 mg/dL. Neonate Population (N=54): Slope 0.96, Intercept 0.01, Correlation Coefficient 0.9982. Range: 0.3 to 24.3 mg/dL. |
| Reference Range | Not explicitly stated as a numerical criterion for the study, but the observed range determined should be clinically acceptable. | The reference range was determined to be 0.3 mg/dL to 1.2 mg/dL. 4 of 40 samples (10%) were outside this range, all being < 0.3 mg/dL. |
| Automated Dilution | A difference between the autodilution mean concentration and the manual dilution mean concentration of ≤ 10% bias. | The Total Bilirubin assay met the acceptance criteria. For Total Bilirubin samples > 25 mg/dL, either System Automated Dilution or Manual Dilution protocol can be performed. |
| Specimen Tube Type | Deming linear regression analysis (slope close to 1, intercept close to 0, high correlation) demonstrating equivalence to the control tube type (serum plastic). | Serum (glass) (N=41): Slope 0.96, Intercept 0.06, Correlation Coefficient 0.9990. SST (N=40): Slope 1.00, Intercept 0.00, Correlation Coefficient 0.9996. EDTA (N=39): Slope 1.00, Intercept -0.01, Correlation Coefficient 0.9990. Lithium Heparin (N=40): Slope 1.01, Intercept 0.02, Correlation Coefficient 0.9994. Lithium Heparin Plasma Separator Tube (PST) (N=40): Slope 0.96, Intercept 0.05, Correlation Coefficient 0.9992. Sodium Heparin (N=39): Slope 0.98, Intercept 0.03, Correlation Coefficient 0.9996. Conclusion: All tested tube types are acceptable, except those containing sodium fluoride/potassium oxalate due to hemolysis potential. |
2. Sample Sizes Used for the Test Set and Data Provenance:
- Limit of Quantitation (LOQ), Limit of Detection (LOD), Limit of Blank (LOB):
- Zero-analyte samples: 4 samples. Tested in a minimum of 5 replicates on 5 separate runs.
- Low-analyte samples: Minimum of 2 samples gravimetrically prepared at 8 target concentrations. Tested in a minimum of 10 replicates on 5 separate runs.
- Data Provenance: Not explicitly stated (e.g., country of origin) but "human serum albumin" and "unconjugated bilirubin" are used. The study is prospective in nature, as samples are prepared for the purpose of the test.
- Linearity: 12 levels per pool in each of three combined bilirubin pools. Tested in a minimum of 4 replicates.
- Data Provenance: "combined bilirubin pools" from "conjugated bilirubin stock" and "unconjugated bilirubin stock", "serum". Prospective.
- Within-Laboratory Precision: 4 control materials (Bio-Rad serum based). Tested in a minimum of 2 replicates, 2 times per day for 20 days.
- Data Provenance: Commercial control materials (Bio-Rad Lyphochek Unassayed Chemistry Control, Bio-Rad Liquichek Pediatric Control). Prospective.
- Interference: Not specified.
- Data Provenance: Not specified, but uses "bilirubin concnetrations". Prospective.
- Method Comparison:
- Adult patient specimens: 124. 4 spiked.
- Neonatal patient specimens: 64. 4 spiked.
- Data Provenance: Patient specimens. Not specified if retrospective or prospective or country of origin, but generally method comparison studies use collected patient samples.
- Reference Range: 40 adult patient serum samples.
- Data Provenance: Fresh, adult patient serum samples from a clinically healthy population. Stored at 2-8°C, protected from light. Assumed to be prospective as samples were collected for the study.
- Automated Dilution Protocol versus Manual Dilution Procedure: Not specified (samples were pooled to create desired concentrations).
- Data Provenance: "Fresh serum specimens" obtained and pooled. Prospective.
- Specimen Tube Type (Matrix Equivalence): Minimum of 40 samples from adult subjects for each tube type. (Serum glass N=41, SST N=40, EDTA N=39, Lithium Heparin N=40, PST N=40, Sodium Heparin N=39).
- Data Provenance: "Fresh or frozen sample sets" from subjects. Assumed to be prospective as these are explicitly collected to test tube types.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts:
- This device is an in vitro diagnostic (IVD) for quantitative measurement. The "ground truth" for such devices is typically established through analytical methods, reference materials, gravimetric preparation, or comparison to a gold standard reference method/device, rather than expert human interpretation.
- Therefore, the concept of "experts used to establish the ground truth" as it applies to image-based AI or clinical diagnostic interpretation by physicians is not applicable here. The ground truth is the chemical concentration of bilirubin.
4. Adjudication Method for the Test Set:
- Again, as this is a quantitative chemical measurement, adjudication methods for expert interpretation (like 2+1, 3+1) are not applicable. The "adjudication" is inherent in the analytical process (e.g., repeating measurements, using certified reference materials, performing statistical analysis of replicates).
5. 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:
- This is an in vitro diagnostic (IVD) device. MRMC studies, which assess human reader performance with and without AI assistance, are typically conducted for AI-powered medical image analysis or clinical decision support systems.
- Therefore, an MRMC comparative effectiveness study is not applicable to this type of device. There are no "human readers" interpreting an output in the same way a radiologist reads an image.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done:
- Yes, this entire submission is a standalone performance evaluation of the assay (the "algorithm only" in a broader sense of the measurement procedure). The device is designed to quantitatively measure bilirubin, and the tests (LOQ, linearity, precision, interference, method comparison) evaluate its analytical performance without direct human interpretive intervention beyond running the instrument and analyzing the data.
7. The Type of Ground Truth Used:
- For LOQ, LOD, LOB: Gravimetrically prepared samples (human serum albumin and unconjugated bilirubin) provide the known "ground truth" concentrations.
- For Linearity: Combined bilirubin pools with known proportional compositions.
- For Precision: Commercial control materials with established (though perhaps unassayed) target ranges, tested repeatedly.
- For Method Comparison: The predicate device's measurements are used as the comparative "ground truth" or reference, as the goal is to show substantial equivalence.
- For Reference Range: Clinical health status of the adult population samples.
- For Automated Dilution: Known target concentrations and manual dilution results.
- For Specimen Tube Type: The control tube type (serum plastic tube) serves as the reference for comparison.
8. The Sample Size for the Training Set:
- This document describes the analytical validation of a re-agent kit for an existing instrument (ARCHITECT c8000 System). It's not an AI model that undergoes "training" in the conventional sense.
- Therefore, the concept of a "training set" for an AI algorithm is not applicable. The development of the reagent and its underlying chemical principles involved R&D and optimization, but not machine learning training on a dataset.
9. How the Ground Truth for the Training Set Was Established:
- As explained above, there is no "training set" in the context of an AI algorithm described here. The "ground truth" used during the development of the assay would have been based on established clinical chemistry principles, reference methods, and gravimetric preparations to ensure accurate concentration measurements during formulation and optimization.
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Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract symbol that resembles three human profiles facing right, stacked on top of each other.
April 2, 2015
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
ABBOTT LABORATORIES SUSHMA RAO REGULATORY AFFAIRS PROJECT MANAGER 1921 HURD DRIVE IRVING TX 75038
Re: K150510
Trade/Device Name: Total Bilirubin Regulation Number: 21 CFR 862.1110 Regulation Name: Bilirubin (total or direct) test system Regulatory Class: II Product Code: CIG, MOM Dated: March 2, 2015 Received: March 3, 2015
Dear Sushma Rao:
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 Parts 801 and 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.
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If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. 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 the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Stayce Beck -S
For:
Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K150510
Device Name Total Bilirubin
Indications for Use (Describe)
The Total Bilirubin assay is used for the quantitation of total bilirubin in human serum or plasma of adults and neonates on the ARCHITECT c8000 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 gall bladder block. A bilirubin (total and unbound) in the neonate test system is a device intended to measure the levels of bilirubin (total and unbound) in the blood (serum) of newborn infants to aid in indicating the risk of bilirubin encephalopathy (kernicterus).
Type of Use (Select one or both, as applicable)
Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
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K150510
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 SMDA 1990 and 21 CFR 807.92.
1. Applicant Name
Sushma Rao, ADD, Regulatory Affairs Project Manager Abbott Laboratories 1921 Hurd Drive Irving, TX 75038 (972) 518-7081 Fax: (972) 518-6960 Email: sushma.rao@abbott.com
Date Summary prepared: April 2, 2015
2. Device Name
Trade Name: Total Bilirubin Device Classification: Class II
Classification Name: Total Bilirubin Reagent Governing Regulation: CFR 862.1110 Product Code: CIG
Classification Name: Bilirubin (total and unbound) in the neonate test system Governing Regulation: 862.1113 Product Code: MQM
3. Predicate Device
Total Bilirubin, K121985
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4. Description of Device
The Total Bilirubin reagent kit contains:
| Number of Bottles × Volume | ||
|---|---|---|
| Component | 7P32-21 | 7P32-41 |
| Reagent 1 (R1) | $10 \times 53$ mL | $8 \times 93$ mL |
| Reagent 2 (R2) | $10 \times 17$ mL | $8 \times 28$ mL |
| Estimated tests per kit* | 2750 | 3840 |
Calculation is based on the minimum reagent fill volume per kit. 米
| Reagent | Reactive Ingredients | Concentration |
|---|---|---|
| Reagent 1 | Surfactants | 10.57% |
| Reagent 1 | HCl | 6.563 g/L |
| Reagent 2 | 2, 4-dichloroaniline | 0.81 g/L |
| Reagent 2 | HCl | 5.563 g/L |
| Reagent 2 | Sodium nitrite | 0.345 g/L |
| Reagent 2 | Surfactant | 1.96% |
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.
5. Indication for Use
The Total Bilirubin assay is used for the quantitation of total bilirubin in human serum or plasma of adults and neonates on the ARCHITECT c8000 System.
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 gall bladder block. A bilirubin (total and unbound) in the neonate test system is a device intended to
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measure the levels of bilirubin (total and unbound) in the blood (serum) of newborn infants to aid in indicating the risk of bilirubin encephalopathy (kernicterus).
6. Comparison of Technological Characteristics
The Total Bilirubin assay is used for the quantitative analysis of total bilirubin in human serum or plasma of adults and neonates on the ARCHITECT c 8000 System.
A comparison of the candidate assay (Total Bilirubin) and the predicate assay (K121985) is presented in the table below.
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Comparison of Total Bilirubin to Predicate Total Bilirubin Assay on the ARCHITECT c8000 Analyzer
| AssayCharacteristics | Total Bilirubin | Predicate Total BilirubinAssay (K121985 ) on theARCHITECT c8000 System | |||
|---|---|---|---|---|---|
| Intended Use | The Total Bilirubin assay is used for | Same | |||
| the quantitative analysis of total | |||||
| bilirubin in human serum or plasma of | |||||
| adults and neonates on the | |||||
| ARCHITECT c 8000 System. | |||||
| Assay Principle | Total (conjugated and unconjugated) | Same | |||
| 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. | |||||
| Detection of | End-point colorimetric | Same | |||
| Analyte | |||||
| Samples | Serum or plasma | Same | |||
| Assay Range | 0.3 to 25.0 mg/dL | 0.1 to 25.0 mg/dL | |||
| Reference Range - | Range (mg/dL) | Same | |||
| Newborn | Premature Newborn | ||||
| < 24 Hours | < 8.0 | ||||
| < 48 Hours | < 12.0 | ||||
| 3 to 5 Days | < 15.0 | ||||
| 7 Days | < 15.0 | ||||
| Full Term Newborn | |||||
| < 24 Hours | < 6.0 | ||||
| < 48 Hours | < 10.0 | ||||
| 3 to 5 Days | < 12.0 | ||||
| 7 Days | < 10.0 | ||||
| Reference Range - | 0.3 to 1.2 mg/dL | 0.2 to 1.2 mg/dL | |||
| Adult | |||||
| Reagent | R1: | R1: | |||
| Formulation | Surfactants | 10.57% | Surfactants | 4.51% | |
| HCl | 6.563 g/L | HCl | 8.204 g/L | ||
| R2: | R2: (Same) | ||||
| 2,4-dichloroaniline | 0.81 g/L | 2,4-dichloroaniline | 0.81 g/L | ||
| HCl | 5.563 g/L | HCl | 5.563 g/L | ||
| Sodium nitrite | 0.345 g/L | Sodium nitrite | 0.345 g/L | ||
| Surfactant | 1.96% | Surfactant | 1.96% |
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7. Summary of Performance Testing
Limit of Blank (LOB), Limit of Detection (LOD), and Limit of Quantitation (LOQ) The study was performed based on guidance from the Clinical and Laboratory Standards Institute (CLSI) document EP17-A2. LoB was determined using 4 samples prepared with human serum albumin (zero-analyte samples). LoD and LoQ were determined using low-level analyte samples prepared from human serum albumin and unconjugated bilirubin. A minimum of 2 low-analyte level samples were gravimetrically prepared at each of the following 8 target concentration levels: 0.010, 0.020, 0.040, 0.080, 0.150, 0.300, 0.450, and 0.600 mg/dL. The zero-analyte samples were tested in a minimum of 5 replicates on 5 separate runs. The low-analyte samples were tested in a minimum of 10 replicates on 5 separate runs. Testing was performed over a minimum of 3 days using 2 lots of reagent, 2 lots of commercially available calibrators, and 1 lot of commercially available controls on 3 ARCHITECT c 8000 instruments. Each reagent lot was matched with a different lot of calibrator.
LOQ is defined as the lowest concentration at which an assay can meet the total allowable error, which includes bias and imprecision. LOQ is based on 180 results meeting the <10% bias acceptance criteria. Therefore, the LOD is equivalent to LOQ.
The LoQ of the Total Bilirubin assay is 0.174 mg/dL. The LoO supports the lower end of the measuring interval of 0.3 mg/dL. LoD is 0.174 mg/dL and LoB is 0.102 mg/dL.
Linearity
Linearity was determined based on guidance from National Committee for Clinical Laboratory Standards (NCCLS) document EP6-A. Three combined bilirubin pools were prepared:
- Pool 1: 75% conjugated bilirubin stock / 25% unconjugated bilirubin stock
- . Pool 2: 50% conjugated bilirubin stock / 50% unconjugated bilirubin stock
- . Pool 3: 25% conjugated bilirubin stock / 75% unconjugated bilirubin stock
A sample set was prepared for each combined bilirubin pool. Each sample set consisted of 12 levels at the following total bilirubin target concentrations: 0.0 (serum), 0.1, 0.5, 2.0, 4.0, 8.0, 12.0, 16.0, 20.0, 22.0, 25.0, and 28.0 mg/dL. Levels 1 through 12 for each
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sample set were tested in a random order in a minimum of 4 replicates using 2 lots reagents and 1 lot each of commercially available calibrators and controls on
1 ARCHITECT c 8000 instrument. All levels in a sample set were tested in the same run.
The Total Bilirubin assay, was demonstrated to be linear across the measuring interval of 0.3 to 25.0 mg/dL
Within-Laboratory Precision (20-Day)
Precision was evaluated using the following Bio-Rad serum based control materials.
- . Level 1: Bio-Rad Lyphochek Unassayed Chemistry Control Level 1
- Level 2: Bio-Rad Lyphochek Unassayed Chemistry Control Level 2 .
- Level 3: Bio-Rad Liquichek Pediatric Control Level 1 •
- . Level 4: Bio-Rad Liquichek Pediatric Control Level 2
The levels were tested in a minimum of 2 replicates 2 times per day (separated by a minimum of 2 hours) for a total of 20 testing days. Testing was performed using 2 lots of reagents and commercially available calibrators and 1 lot of commercially available controls on 2 ARCHITECT c 8000 instruments. During each run, a given reagent lot/calibrator lot combination was randomly tested. Therefore, for each instrument, the 20 days of testing included up to 4 instrument/reagent lot combinations.
The analysis was performed based on guidance from National Committee for Clinical Laboratory Standards (NCCLS) document EP5-A2.
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Results Table:
| Within Run | Total | |||||
|---|---|---|---|---|---|---|
| Sample | N | Mean(mg/dL) | SD(mg/dL) | %CV | SD(mg/dL) | %CV |
| 1 | 80 | 0.87 | 0.010 | 1.2 | 0.018 | 2.1 |
| 2 | 80 | 4.53 | 0.034 | 0.8 | 0.057 | 1.3 |
| 3 | 80 | 6.42 | 0.041 | 0.6 | 0.066 | 1.0 |
| 4 | 80 | 16.85 | 0.115 | 0.7 | 0.204 | 1.2 |
| Within Run | Total | |||||
| Sample | N | Mean(µmol/L) | SD(µmol/L) | %CV | SD(µmol/L) | %CV |
| 1 | 80 | 14.90 | 0.17 | 1.2 | 0.31 | 2.1 |
| 2 | 80 | 77.57 | 0.58 | 0.8 | 0.97 | 1.3 |
| 3 | 80 | 109.93 | 0.70 | 0.6 | 1.13 | 1.0 |
Interference
The interference study was performed based on guidance from CLSI document EP7-A2. Interference effects were assessed by dose response and paired difference methods at two total bilirubin concnetrations (15mg/dL and 1.2 mg/dL, respectively). A bias of > 10%, or > 0.2 mg/dL (> 3.4 umol/L) for bilirubin concentrations ≤ 2.0 mg/dL is considered significant interference.
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| Interferent | Bilirubin | |||
|---|---|---|---|---|
| InterferingSubstance | InterferentConcentration | Control(mg/dL) | Observed Diff(mg/dL) | (%) |
| Hemoglobin | 2000 mg/dL | 1.0 | -0.1 | -9.8 |
| Hemoglobin | 2000 mg/dL | 13.4 | -0.4 | -3.0 |
| Intralipid | 1000 mg/dL | 1.0 | 0.0 | -0.6 |
| Intralipid | 1000 mg/dL | 13.4 | -0.1 | -0.6 |
| Indican | 0.125 mmol/L | 0.9 | 0.2 | 26.7 |
| Indican | 0.25 mmol/L | 14.7 | 0.5 | 3.2 |
| Interferent | Bilirubin | |||
| InterferingSubstance | InterferentConcentration | Control(µmol/L) | Observed Diff(µmol/L) | (%) |
| Hemoglobin | 20 g/L | 17.1 | -1.7 | -9.8 |
| Hemoglobin | 20 g/L | 229.1 | -6.8 | -3.0 |
| Intralipid | 10 g/L | 17.1 | 0.0 | -0.6 |
| Intralipid | 10 g/L | 229.1 | -1.7 | -0.6 |
| Indican | 0.125 mmol/L | 15.4 | 3.4 | 26.7 |
Results Tables: (Conventional and International Units)
Indican, at concentrations > 0.125 mmol/L, interferes with the assay in samples with bilirubin levels at 1.2 mg/dL.
Method Comparison
The study was performed based on guidance from CLSI document EP09-A2-IR. A total of 124 adult patient specimens and 64 neonatal patient specimens were evaluated with the candidate Total Bilirubin assay and the predicate Total Bilirubin (K121985) assay. A total of 4 adult and 4 neonate patient samples were spiked. Each sample was tested using 2 lots each of the candidate Total Bilirubin assay and the predicate Total Bilirubin (K121985) reagents and 1 lot each of commercially available calibrators and controls. Testing was performed in duplicate on the candidate Total Bilirubin assay and in duplicate on the predicate Total Bilirubin assay over 5 separate days on 1 ARCHITECT c 8000 System. Passing-Bablok regression results based on singlet test results from a representative reagent lot are summarized below:
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Adult Population Representative Data
| N | Slope | Intercept | CorrelationCoefficient | Range(mg/dL) |
|---|---|---|---|---|
| 118 | 0.99 | -0.09 | 0.9994 | 0.3 to 24.8 |
Neonate Population Representative Data
| N | Slope | Intercept | CorrelationCoefficient | Range(mg/dL) |
|---|---|---|---|---|
| 54 | 0.96 | 0.01 | 0.9982 | 0.3 to 24.3 |
Reference Range
The study was performed based on guidance from CLSI document EP28-A3c. Fresh, adult patient serum samples from a clinically healthy population of non-distinguished adult male and female patients were obtained. The samples were stored at 2 to 8℃ and protected from light when not in use. The samples were up to 3 days old when received at the testing site. The samples were tested on the day they were received at the testing site. The samples were tested in a replicate of 1 using 1 lot of reagents and 1 lot each of commercially available calibrators and controls on 1 ARCHITECT c 8000 instrument.
The Total Bilirubin assay, which had a total of 4 of 40 samples (10%) outside the reference range (all out-of-range samples were < 0.3 mg/dL).
The reference range was determined to be 0.3 mg/dL to 1.2 mg/dL.
Automated Dilution Protocol versus Manual Dilution Procedure
Fresh serum specimens were obtained and, if necessary, pooled to create test samples at the following target total bilirubin concentrations: 34, 32, 30, 28, 26, and 24 mg/dL. The samples were divided into 3 portions. One portion of each sample was tested using the 1:5 and 1:10 autodilution protocols. Two portions were manually diluted using 0.85% saline solution, one at 1:5 and the other at 1:10. All portions were tested in replicates of
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6 in the same run as the autodiluted samples using 1 lot of reagents on one ARCHITECT c 8000 System.
The Total Bilirubin assay met the acceptance criteria of a difference between the autodilution mean concentration and the manual dilution mean concentration of ≤ 10% bias. For Total Bilirubin samples greater than 25 mg/dL, either the System Automated Dilution protocol or Manual Dilution protocol can be performed.
Specimen Tube Type (Matrix Equivalence)
The study was performed based on guidance from CLSI document EP9-A3 and CLSI document GP34-A. The study control tube type was the serum plastic tube. The following tubes types were under evaluation: serum with gel separator, K2 EDTA plasma (without gel separator), lithium heparin plasma (without gel separator), lithium heparin plasma with gel separator, and sodium heparin plasma (without gel separator). Fresh or frozen sample sets were obtained that included the control tube type and at least 1 tube type under evaluation. Each tube type under evaluation was assessed using a minimum of 40 samples from adult subjects. The sample sets spanned the assay's measuring interval. All samples were tested in replicates of 6 using 1 lot each of reagents and commercially available calibrators and controls on 1 ARCHITECT c 8000 System. All samples collected from the same subject were tested in the same run.
Deming linear regression analysis was performed using the first set of results obtained. Results summarized below demonstrated that the following blood collection tube types are acceptable for use with the Total Bilirubin assay:
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| Tube Type | N | Slope | Intercept | CorrelationCoefficient |
|---|---|---|---|---|
| Serum (glass) | 41 | 0.96 | 0.06 | 0.9990 |
| Serum Separator Tube (SST) | 40 | 1.00 | 0.00 | 0.9996 |
| Ethylenediaminetetraacetic Acid(EDTA) | 39 | 1.00 | -0.01 | 0.9990 |
| Lithium Heparin | 40 | 1.01 | 0.02 | 0.9994 |
| Lithium Heparin PlasmaSeparator Tube (PST) | 40 | 0.96 | 0.05 | 0.9992 |
| Sodium Heparin | 39 | 0.98 | 0.03 | 0.9996 |
Tube type limitation: Tubes containing sodium flouride/potassium oxalate are not recommended due to the potential for hemolysis.
8. Conclusion Drawn from Performance Testing
The results presented in this 510(k) premarket notification demonstrate that the candidate Total Bilirubin assay performance is substantially equivalent to the predicate assay (Total Bilirubin, K121985).
§ 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.