(255 days)
No
The summary describes a standard photometric chemical assay for measuring direct bilirubin. There is no mention of AI, ML, image processing, or any other technology typically associated with AI/ML in medical devices. The performance studies are based on traditional analytical methods.
No.
The device is an in vitro diagnostic (IVD) assay used for the quantitative determination of direct bilirubin, which aids in the diagnosis and treatment of certain disorders. It does not provide therapy or treatment to a patient.
Yes
The "Intended Use / Indications for Use" section explicitly states that the assay is for "in vitro diagnostic use in the quantitative determination of direct bilirubin in human serum and plasma." It also mentions that the measurement is "used in the diagnosis and treatment of liver, hemolytic-hematological, and metabolic disorders."
No
The device description clearly states it is a "Photometric test using 2,4-dichloroaniline (DCA)" and measures absorbance at specific wavelengths, indicating a chemical reagent and optical hardware component, not a software-only device.
Yes, this device is an IVD (In Vitro Diagnostic).
The "Intended Use / Indications for Use" section explicitly states:
"The Atellica® CH Diazo Direct Bilirubin (D DBil) assay is for in vitro diagnostic use in the quantitative determination of direct bilirubin in human serum and plasma using the Atellica® CH Analyzer."
This statement clearly indicates that the device is intended for use in diagnostic procedures performed outside of the living body, which is the definition of an in vitro diagnostic device.
N/A
Intended Use / Indications for Use
The Atellica® CH Diazo Direct Bilirubin (D DBil) assay is for in vitro diagnostic use in the quantitative determination of direct bilirubin in human serum and plasma using the Atellica® CH Analyzer. Measurement of direct 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
Atellica® CH Diazo Direct Bilirubin is a Photometric test using 2,4-dichloroaniline (DCA). Direct bilirubin in presence of diazotized 2,4-dichloroaniline forms a red colored azocompound in acidic solution. Absorbance is measured at 545/658 nm.
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
Not Found
Intended User / Care Setting
Prescription Use Only
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)
Detection Capability:
The Limit of Blank (LoB) corresponds to the highest measurement result that is likely to be observed for a blank sample. The assay is designed to have an LoB ≤ Limit of Detection (LoD). The Limit of Detection (LoD) corresponds to the lowest concentration of direct bilirubin that can be detected with a probability of 95%. The assay is designed to have an LoD ≤ Limit of Quantitation(LoQ). The Limit of Quantitation (LoQ) corresponds to the lowest concentration of direct bilirubin that met the required analyte level but did not reach 20%CV. The assay is designed to have a LoQ of ≤ 0.10mg/dL.
Detection capability was determined in accordance with CLSI Documents EP17-A2.
Serum/Plasma: LoB 0.00 mg/dL, LoD 0.02 mg/dL, LoQ 0.10 mg/dL.
Precision:
Precision was determined in accordance with CLSI Document EP05-A3. Samples were assayed on the Atellica CH Analyzer in duplicate in 2 runs per day for 20 days.
Results:
Serum 1 (N=80, Mean=0.37 mg/dL): Repeatability SD=0.007 mg/dL (1.9% CV), Within-Lab SD=0.007 mg/dL (1.9% CV).
Serum 2 (N=80, Mean=0.99 mg/dL): Repeatability SD=0.004 mg/dL (0.4% CV), Within-Lab SD=0.007 mg/dL (0.7% CV).
Serum 3 (N=80, Mean=4.95 mg/dL): Repeatability SD=0.014 mg/dL (0.3% CV), Within-Lab SD=0.037 mg/dL (0.7% CV).
Serum 4 (N=80, Mean=9.16 mg/dL): Repeatability SD=0.031 mg/dL (0.3% CV), Within-Lab SD=0.070 mg/dL (0.8% CV).
Reproducibility:
Reproducibility was determined in accordance with CLSI Document EP05-A3. Samples were assayed with 5 replicates per run for 5 days using 3 instruments/sites and 3 reagent lots.
Results:
Serum (N=225, Mean=0.36 mg/dL): Repeatability SD=0.006 mg/dL (1.7% CV), Between-Day SD=0.001 mg/dL (0.3% CV), Between-LOT SD=0.009 mg/dL (2.5% CV), Between SYSTEM SD=0.002 mg/dL (0.6% CV), Reproducibility SD=0.011 mg/dL (3.1% CV).
Serum (N=225, Mean=0.97 mg/dL): Repeatability SD=0.005 mg/dL (0.5% CV), Between-Day SD=0.005 mg/dL (0.5% CV), Between-LOT SD=0.012 mg/dL (1.2% CV), Between SYSTEM SD=0.008 mg/dL (0.8% CV), Reproducibility SD=0.016 mg/dL (1.6% CV).
Serum (N=225, Mean=5.02 mg/dL): Repeatability SD=0.017 mg/dL (0.3% CV), Between-Day SD=0.016 mg/dL (0.3% CV), Between-LOT SD=0.118 mg/dL (2.4% CV), Between SYSTEM SD=0.051 mg/dL (1.0% CV), Reproducibility SD=0.131 mg/dL (2.6% CV).
Serum (N=225, Mean=9.37 mg/dL): Repeatability SD=0.027 mg/dL (0.3% CV), Between-Day SD=0.026 mg/dL (0.3% CV), Between-LOT SD=0.290 mg/dL (3.1% CV), Between SYSTEM SD=0.072 mg/dL (0.8% CV), Reproducibility SD=0.301 mg/dL (3.2% CV).
Assay Comparison:
The Atellica CH Diazo Direct Bilirubin (D DBil) assay was designed to have correlation coefficient of ≥ 0.950 and a slope of 1.00 ± 0.10 compared to the Wako Direct Billrubin V assay.
Results: Serum (N=100), Comparison Assay: Wako Direct Bilirubin V, Regression Equation: y=0.95x-0.03 mg/dL, Sample Range: 0.10 - 11.10 mg/dL, Correlation coefficient (r): 0.993.
Specimen Equivalency:
The specimen equivalency was determined using the Deming regression model in accordance with CLSI Document EP90c.
Results:
Plasma (Lithium heparin) vs Serum: N=53, Regression Equation: y=1.00x - 0.02, Sample Range: 0.10 - 10.27 mg/dL, r=0.999.
Plasma (Sodium Heparin) vs Serum: N=53, Regression Equation: y=0.98x + 0.00, Sample Range: 0.10 - 10.27 mg/dL, r=0.999.
Plasma K2(EDTA) vs Serum: N=53, Regression Equation: y=0.98x - 0.02, Sample Range: 0.10 - 10.27 mg/dL, r=0.999.
Interferences:
The Atellica CH Diazo Direct Bilirubin (D DBil) assay is designed to have ≤ 10% interference from hemoglobin, bilirubin, and lipemia. Bias is the difference in the results between the control sample (does not contain the interferent) and the test sample (contains the interferent) expressed in a percentage. Bias > 10% is considered interference. Interference testing was performed in accordance with CLSI Document EP07.
Hemoglobin: Interference observed at concentrations ≥ 37.5 mg/dL. For example, at 37.5 mg/dL Hemoglobin and 4.50 mg/dL Analyte, bias was -12.2%.
Lipemia: No interference up to 1000 mg/dL.
Non-interfering Substances: Acetaminophen (20 mg/dL), Acetylsalicylic acid (100 mg/dL), Albumin (6 g/dL), Ascorbic acid (5 mg/dL), Carbenicillin (3 mg/dL), Cholesterol (500 mg/dL), Diazepam (20 µg/mL), Eltrombopag (25 µg/mL), Ethanol (800 mg/dL), Ibuprofen (50 mg/dL), IgG (5 g/dL), Levodopa (300 µg/mL), Oxytetracycline (50 mg/dL), Phloroglucinol (1500 ng/mL), Rheumatoid Factor (510 IU/mL), Rifampicin (6 mg/dL), Total Protein (12 g/dL) show bias ≤ 10%.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Not Found
Predicate Device(s)
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 862.1110 Bilirubin (total or direct) test system.
(a)
Identification. A bilirubin (total or direct) test system is a device intended to measure the levels of bilirubin (total or direct) in plasma or serum. Measurements of the levels of bilirubin, an organic compound formed during the normal and abnormal distruction of red blood cells, if used in the diagnosis and treatment of liver, hemolytic hematological, and metabolic disorders, including hepatitis and gall bladder block.(b)
Classification. Class II.
0
Image /page/0/Picture/0 description: The image shows 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 includes the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue text.
June 12, 2023
Siemens Healthcare Diagnostics Inc. Anthony Calabro Regulatory Affairs Specialist 500 GBC Drive, M/S 514, PO Box 6101 Newark, Delaware 19714
Re: K223078
Atellica® CH Diazo Direct Bilirubin (D DBil) Trade/Device Name: Regulation Number: 21 CFR 862.1110 Regulation Name: Bilirubin (Total Or Direct) Test System Regulatory Class: Class II Product Code: CIG Dated: February 21, 2023 Received: February 21, 2023
Dear Anthony Calabro:
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 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 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 mediation-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,
Paula V. Caposino -S
Paula Caposino, Ph.D. Acting Deputy 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
2
Indications for Use
Submission Number (if known)
K223078 Device Name
Atellica® CH Diazo Direct Bilirubin (D DBil)
Indications for Use (Describe)
The Atellica® CH Diazo Direct Bilirubin (D DBil) assay is for in vitro diagnostic use in the quantitative determination of direct bilirubin in human serum and plasma using the Atellica® CH Analyzer. Measurement of direct 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.
Type of Use (Select one or both, as applicable)
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
3
This 510(k) Summary of Safety and Effectiveness is being submitted in accordance with the requirements of 21 CFR 807.92 and the Safe Medical Device Act of 1990.
The assigned 510(k) Number is: K223078
1. Date Prepared
June 9, 2023
2. Applicant Information
| Contact: | Anthony Calabro
Regulatory Affairs Specialist |
|----------|----------------------------------------------------------------------------------------|
| Address: | Siemens Healthcare Diagnostics Inc.
P.O. Box 6101, M/S 514
Newark, DE 19714-1601 |
| Email: | anthony.calabro@siemens-healthineers.com |
3. Regulatory Information
Atellica® CH Diazo Direct Bilirubin (D_DBil) assay
Trade Name: Atellica® CH Diazo Direct Bilirubin (D DBil) Common Name: Bilirubin (total or direct) test system Classification Name: Diazo Colorimetry, Bilirubin FDA Classification: Class II Review Panel: Chemistry Product Code: CIG Regulation Number: 21 CFR 862.1110
4. Predicate Device Information
Predicate Device Name: Wako Direct Bilirubin V 510(k) Number: K053132
4
5. Intended Use / Indications For Use
The Atellica® CH Diazo Direct Bilirubin (D_DBil) assay is for in vitro diagnostic use in the quantitative determination of direct bilirubin in human serum and plasma using the Atellica® CH Analyzer. Measurement of direct bilirubin, an organic compound formed during the normal and abnormal destruction of red blood cells, is used in the diagnosis and treatment of liver, hemolytichematologcial, and metabolic disorders, including hepatitis and gall bladder block.
Special Conditions for Use Statement: For Prescription Use Only
6. Device Description
Atellica® CH Diazo Direct Bilirubin is a Photometric test using 2,4-dichloroaniline (DCA). Direct bilirubin in presence of diazotized 2,4-dichloroaniline forms a red colored azocompound in acidic solution. Absorbance is measured at 545/658 nm.
7. Purpose of Submission
The purpose of this submission is a premarket notification for a new device: Atellica CH Diazo Direct Bilirubin (D DBil) assay
8. Comparison of Candidate Device and Predicate Device
The table below describes the similarities and differences between the Atellica CH Diazo Direct Bilirubin assay (Candidate Device) and the Wako Direct Bilirubin V (Predicate Device).
Substantial equivalence was demonstrated by testing several performance characteristics including intended use/indications for use, specimen types, units of measure, expected values, and measuring interval.
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| Feature | Candidate Device | Predicate Device |
|---|---|---|
| Atellica® CH Diazo Direct Bilirubin (D_DBil) | Wako Direct Bilirubin V | |
| (K053132) | ||
| Intended Use | The Atellica CH Diazo Direct Bilirubin | |
| (D_DBil) assay is for in vitro diagnostic use | ||
| in the quantitative determination of direct | ||
| bilirubin in human serum and plasma using | ||
| the Atellica CH Analyzer. Measurement of | ||
| direct 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-hematologcial, and metabolic | ||
| disorders, including hepatitis and gall | ||
| bladder block. | For in vitro diagnostic use in the | |
| quantitative determination of | ||
| direct bilirubin in human serum or | ||
| plasma. Such measurements are | ||
| useful in the screening of liver | ||
| function disorders or in the | ||
| diagnosis of jaundice. | ||
| Sample Type | Human serum and plasma (lithium heparin, | |
| sodium heparin, dipotassium EDTA) | Human Serum and plasma (Lithium | |
| heparin) | ||
| Units of Measure | mg/dL | mg/dL |
| Assay Range / Measuring | ||
| Interval | 0.10 mg/dL -12.00 mg/dL | 0.1-20.0 mg/dL |
| Expected Values | ≤ 0.30 mg/dL (5.13 µmol/L). | ≤ 0.30 mg/dL (5.13 µmol/L). |
| Feature | Candidate Device | Predicate Device |
|---|---|---|
| Atellica® CH Diazo Direct Bilirubin (D_DBil) | Wako Direct Bilirubin V (K053132) | |
| Assay Principle | Photometric test using 2,4-dichloroaniline (DCA). | |
| Direct bilirubin in presence of diazotized 2,4- | ||
| dichloroaniline forms a red colored | ||
| azocompound in acidic solution. Absorbance is | ||
| measured at 545/658 nm. | Bilirubin is oxidized by vanadate at about | |
| pH 3 to produce biliverdin. In the presence | ||
| of detergent and vanadate, conjugated | ||
| (direct) bilirubin is oxidized. This oxidation | ||
| reaction causes a decrease in the optical | ||
| density of the yellow color, which is | ||
| specific to bilirubin. The decrease in | ||
| optical density at 451/545 nm is | ||
| proportional to the direct bilirubin | ||
| concentration in the sample. The | ||
| concentration is measured as an endpoint | ||
| reaction. | ||
| Traceability | Traceable to internal reference standards | |
| manufactured by gravimetric methods | Traceable to reference method, which | |
| uses reference materials from the National | ||
| Institute of Standards and Technology | ||
| (NIST). | ||
| Feature | Candidate Device | Predicate Device |
| Atellica® CH Diazo Direct Bilirubin (D_DBil) | Wako Direct Bilirubin V (K053132) | |
| Calibration | Single level calibration | Single level calibration |
| Calibrators | Atellica CH Bilirubin Calibrator (BILI CAL) | Siemens Chemistry Calibrator |
| Reagents | Two liquid reagents, ready to use | Ready-for-use liquid reagents |
| Composition | Pack 1: | Direct Bilirubin Reagent 1: |
| Well 1 Reagent 1: | ||
| 23.5mL | ||
| EDTA-NA2(0.1 mmoll/L); NaCl (150mmol/L); sulfamic | ||
| acid (100 mmol/L) | 68 mL in 70-mLcontainers | |
| Tartrate buffer, pH 2.9 | ||
| (0.1 mol/L)Detergent | ||
| Well 2 Reagent 1: | ||
| 23.5mL | ||
| EDTA-NA2(0.1 mmoll/L); NaCl (150mmol/L); sulfamic | ||
| acid (100 mmol/L) | Direct Bilirubin Reagent 2: | |
| 25 mL in 70-mL containers | ||
| Phosphate buffer, pH 7.0(10 | ||
| mmol/L)Sodium metavanadate (4 mmol/L) | ||
| Pack 2: | ||
| Well 1 Reagent 2: | ||
| 8.8mL | ||
| 2,4-Dichloroaniline (5 mmol/L); HCl (920mmol/L); | ||
| EDTA-Na2 (0.13mmol/L); Na-Nitrite (0.5 mmol/L) | ||
| Well 2 Reagent 2: | ||
| 8.8mL | ||
| 2,4-Dichloroaniline (5 mmol/L); HCl (920mmol/L); | ||
| EDTA-Na2 (0.13mmol/L); Na-Nitrite (0.5 mmol/L) | ||
| Interferences | Hemoglobin: | Hemoglobin: |
| No Interference ≤ 12.5 mg/dL | No Interference ≤ 750 mg/dL | |
| Lipemia: | Lipemia: | |
| No Interference ≤ 1000 mg/dL | No Interference ≤ 1000mg/dL |
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7
9. Standard/Guidance Document References
The following recognized standards from Clinical Laboratory Standards Institute (CLSI) were used as a basis of the study procedures described in this submission:
• Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline—Third Edition. (CLSI EP05-A3).
· Interference Testing in Clinical Chemistry (CLSI EP07).
• Measurement Procedure Comparison and Bias Estimation Using Patient Samples (CLS) EP09-A3).
• Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline-Second Edition (EP17-A2).
- · Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline (CLSI EP25-A).
- Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory;
- Approved Guideline Third Edition (CLSI EP28-A3c).
- Establishing and Verifying an Extended Measuring Interval Through Specimen Dilution and Spiking (CLSI EP34-ED1)
- · Metrological Traceability and Its Implementation; CLSI EP32-R)
- Supplemental tables for Interference Testing in Clinical Chemistry (CLSI EP37-ED1)
- Evaluation of the Linearity of Quantitative Measurement Procedures -20d Edition (CLSI EP06 ED2)
10. Performance Characteristics for Atellica ® CH Diazo Direct Bilirubin (D DBil)
10.1 Detection Capability
The Limit of Blank (LoB) corresponds to the highest measurement result that is likely to be observed for a blank sample. The assay is designed to have an LoB ≤ Limit of Detection (LoD).
The Limit of Detection (LoD) corresponds to the lowest concentration of direct bilirubin that can be detected with a probability of 95%. The assay is designed to have an LoD ≤ Limit of Quantitation(LoQ).
The Limit of Quantitation (LoQ) corresponds to the lowest concentration of direct bilirubin that met the required analyte level but did not reach 20%CV. The assay is designed to have a LoQ of ≤ 0.10mg/dL.
Detection capability was determined in accordance with CLSI Documents EP17-A2.
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The following results were obtained:
| Specimen Type | Detection Capability | Result mg/dL |
|---|---|---|
| Serum/Plasma | LoB | 0.00 |
| LoD | 0.02 | |
| LoQ | 0.10 |
10.2 Precision
Precision was determined in accordance with CLSI Document EP05-A3. Samples were assayed on the Atellica CH Analyzer in duplicate in 2 runs per day for 20 days. The following results were obtained.
| Mean | Repeatability | Within-Lab | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Specimen | |||||||||
| Type | N | Mean | |||||||
| (mg/dL) | Mean | ||||||||
| (µmol/L) | SD | ||||||||
| (mg/dL) | SD | ||||||||
| (µmol/L) | CV | ||||||||
| (%) | SD | ||||||||
| (mg/dL) | SD | ||||||||
| (µmol/L) | CV | ||||||||
| (%) | |||||||||
| Serum 1 | 80 | 0.37 | 6.33 | 0.007 | 0.120 | 1.9 | 0.007 | 0.120 | 1.9 |
| Serum 2 | 80 | 0.99 | 16.93 | 0.004 | 0.068 | 0.4 | 0.007 | 0.120 | 0.7 |
| Serum 3 | 80 | 4.95 | 84.65 | 0.014 | 0.239 | 0.3 | 0.037 | 0.633 | 0.7 |
| Serum 4 | 80 | 9.16 | 156.64 | 0.031 | 0.530 | 0.3 | 0.070 | 1.197 | 0.8 |
10.3 Reproducibility
Reproducibility was determined in accordance with CLSI Document EP05-A3. Samples were assayed with 5 replicates per run for 5 days using 3 instruments/sites and 3 reagent lots. The data was analyzed to calculate the following components of precision: repeatability, between-day, between-lot, between-instrument, and reproducibility (total). The following results were obtained.
| Specimen
Type | N | Mean
mg/dL | Mean
µmol/L | Repeatability | | | Between-Day | | | Between-LOT | | | Between SYSTEM | | | Reproducibility | | |
|------------------|-----|---------------|----------------|---------------|--------------|---------|-------------|--------------|---------|-------------|--------------|---------|----------------|--------------|---------|-----------------|--------------|---------|
| | | | | SD
mg/dL | SD
µmol/L | %
CV | SD
mg/dL | SD
µmol/L | %
CV | SD
mg/dL | SD
µmol/L | %
CV | SD
mg/dL | SD
µmol/L | %
CV | SD
mg/dL | SD
µmol/L | %
CV |
| Serum | 225 | 0.36 | 6.16 | 0.006 | 0.103 | 1.7 | 0.001 | 0.017 | 0.3 | 0.009 | 0.154 | 2.5 | 0.002 | 0.034 | 0.6 | 0.011 | 0.188 | 3.1 |
| Serum | 225 | 0.97 | 16.59 | 0.005 | 0.086 | 0.5 | 0.005 | 0.086 | 0.5 | 0.012 | 0.205 | 1.2 | 0.008 | 0.137 | 0.8 | 0.016 | 0.274 | 1.6 |
| Serum | 225 | 5.02 | 85.84 | 0.017 | 0.291 | 0.3 | 0.016 | 0.274 | 0.3 | 0.118 | 2.018 | 2.4 | 0.051 | 0.872 | 1.0 | 0.131 | 2.240 | 2.6 |
| Serum | 225 | 9.37 | 160.23 | 0.027 | 0.462 | 0.3 | 0.026 | 0.445 | 0.3 | 0.290 | 4.959 | 3.1 | 0.072 | 1.231 | 0.8 | 0.301 | 5.147 | 3.2 |
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10.4 Assay Comparison
The Atellica CH Diazo Direct Bilirubin (D DBil) assay was designed to have correlation coefficient of ≥ 0.950 and a slope of 1.00 ± 0.10 compared to the Wako Direct Billrubin V assay. The following results were obtained.
| Specimen
Type | Comparison
Assay (x) | Regression Equation
mg/dL ( $\u03bcmol$ /L) | Sample Range
mg/dL ( $\u03bcmol$ /L) | N | r |
|------------------|----------------------------|------------------------------------------------|-----------------------------------------|-----|-------|
| Serum | Wako Direct
Bilirubin V | $y=0.95x-0.03mg/dL$ $(y=0.95x-.51)\u03bcmol/L$ | 0.10 - 11.10
(1.71 - 189.81) | 100 | 0.993 |
N – Number of samples
r – Correlation coefficient
10.5 Specimen Equivalency
The specimen equivalency was determined using the Deming regression model in accordance with CLSI Document EP90c. The following results were obtained:
| Specimen
Type | Reference
Specimen | Regression Equation
mg/dL (µmol/L) | Sample Range
mg/dL (µmol/L) | N | r |
|--------------------------------|-----------------------|------------------------------------------|---------------------------------|----|-------|
| Plasma
(Lithium
heparin) | Serum | $y=1.00x - 0.02$
( $y=1.00x - 0.34$ ) | 0.10 - 10.27
(1.71 - 175.62) | 53 | 0.999 |
| Plasma
(Sodium
Heparin) | Serum | $y=0.98x + 0.00$
( $y=0.98 + 0.00$ ) | 0.10 - 10.27
(1.71 - 175.62) | 53 | 0.999 |
| Plasma
K2(EDTA) | Serum | $y=0.98x - 0.02$
( $y=0.98x - 0.34$ ) | 0.10 - 10.27
(1.71 - 175.62) | 53 | 0.999 |
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10.6 Interferences
10.6.1 Hemolysis, Icterus, and Lipemia (HIL)
The Atellica CH Diazo Direct Bilirubin (D DBil) assay is designed to have ≤ 10% interference from hemoglobin, bilirubin, and lipemia. Bias is the difference in the results between the control sample (does not contain the interferent) and the test sample (contains the interferent) expressed in a percentage. Bias > 10% is considered interference. Analyte results should not be corrected based on this bias.
Interference testing was performed in accordance with CLSI Document EP07. The following results were obtained:
Interferent concentrations in the table below are the highest concentration tested with no interference.
| Substance | Substance Concentration
Conventional Units (SI Units) | Analyte Concentration
Conventional Units (SI Units) | Bias |
|------------|----------------------------------------------------------|--------------------------------------------------------|-------------|
| Hemoglobin | 12.5 mg/dL (0.125 g/L) | 0.33 mg/dL (5.64 μmol/L) | -0.10 mg/dL |
| Hemoglobin | 12.5 mg/dL (0.125 g/L) | 4.84 mg/dL (82.76 μmol/L) | -6.2% |
| Hemoglobin | 25.0 mg/dL (0.250 g/L) | 0.31 mg/dL (5.30 μmol/L) | -0.07 mg/dL |
| Hemoglobin | 25.0 mg/dL (0.250 g/L) | 4.50 mg/dL (76.95 μmol/L) | -8.0% |
| Hemoglobin | 37.5 mg/dL (0.375 g/L) | 0.31 mg/dL (5.30 μmol/L) | -0.11 mg/dL |
| Hemoglobin | 37.5 mg/dL (0.375 g/L) | 4.50 mg/dL (76.95 μmol/L) | -12.2% |
| Hemoglobin | 50.0 mg/dL (0.500 g/L) | 0.31 mg/dL (5.30 μmol/L) | -0.14 mg/dL |
| Hemoglobin | 50.0 mg/dL (0.500 g/L) | 4.50 mg/dL (76.95 μmol/L) | -15.1% |
| Hemoglobin | 75.0 mg/dL (0.750 g/L) | 0.31 mg/dL (5.30 μmol/L) | -0.17 mg/dL |
| Hemoglobin | 75.0 mg/dL (0.750 g/L) | 4.50 mg/dL (76.95 μmol/L) | -22.3% |
| Hemoglobin | 112.5 mg/dL (1.125 g/L) | 0.31 mg/dL (5.30 μmol/L) | -0.19 mg/dL |
| Hemoglobin | 112.5 mg/dL (1.125 g/L) | 4.50 mg/dL (76.95 μmol/L) | -30.8% |
| Hemoglobin | 125.0 mg/dL (1.250 g/L) | 0.31 mg/dL (5.30 μmol/L) | -0.20 mg/dL |
| Hemoglobin | 125.0 mg/dL (1.250 g/L) | 4.50 mg/dL (76.95 μmol/L) | -32.8% |
| Hemoglobin | 150.0 mg/dL (1.500 g/L) | 0.31 mg/dL (5.30 μmol/L) | -0.20 mg/dL |
| Hemoglobin | 150.0 mg/dL (1.500 g/L) | 4.50 mg/dL (76.95 μmol/L) | -36.8% |
| Hemoglobin | 250.0 mg/dL (2.500 g/L) | 0.31 mg/dL (5.30 μmol/L) | -0.25 mg/dL |
| Hemoglobin | 250.0 mg/dL (2.500 g/L) | 4.50 mg/dL (76.95 μmol/L) | -46.2% |
| Hemoglobin | 375.0 mg/dL (3.750 g/L) | 0.31 mg/dL (5.30 μmol/L) | -0.26 mg/dL |
| Hemoglobin | 375.0 mg/dL (3.750 g/L) | 4.50 mg/dL (76.95 μmol/L) | -54.0% |
| Hemoglobin | 500.0 mg/dL (5.000 g/L) | 0.31 mg/dL (5.30 μmol/L) | -0.26 mg/dL |
| Hemoglobin | 500.0 mg/dL (5.000 g/L) | 4.50 mg/dL (76.95 μmol/L) | -59.0% |
| Lipemia | 1000 mg/dL (10.00g/L) | 0.31 mg/dL (3.50 μmol/L) | -0.07 mg/dL |
| Lipemia | 1000 mg/dL (10.00g/L) | 4.55 mg/dL (77.81 μmol/L) | -4.8% |
11
Do not use hemolyzed samples, as they may cause significant interference with this assay. Hemolyzed samples will give falsely negative results.
An H index above 0 (≥1) indicates hemolysis has been detected and results should not be reported out of the laboratory. It is strongly recommended that the HIL index capability be turned on in order to detect hemolysis in samples.
Assay results obtained at individual laboratories may vary from the data presented.
12
10.6.2 Non-interfering Substances
The following substances do not interfere with Atellica CH Diazo Direct Bilirubin (D_DBil) assay when present in serum and plasma at the concentrations indicated in the table below. Bias due to these substances is ≤ 10%.
Interference testing was performed in accordance with CLSI Document EP07. The following results were obtained:
| Interferent | Interferent
Concentration
(SI) | Observed
Analyte (SI) | Observed
Bias from
Control |
|----------------------|--------------------------------------|------------------------------|----------------------------------|
| Acetaminophen | 20 mg/dL | 0.29 mg/dL | |
| | (1323.1 µmol/L) | (4.96 µmol/L) | -0.01 mg/dL |
| Acetaminophen | 20 mg/dL | 5.23 mg/dL | |
| | (1323.1 µmol/L) | (89.43 µmol/L) | -1.0% |
| Acetylsalicylic acid | 100 mg/dL | 0.29 mg/dL | |
| | (5555.6 µmol/L) | (4.96 µmol/L) | -0.01 mg/dL |
| Acetylsalicylic acid | 100 mg/dL | 5.21 mg/dL | |
| | (5555.6 µmol/L) | (89.09 µmol/L) | 0.0% |
| Albumin | 6 g/dL | 0.29 mg/dL | |
| | (60 g/L) | (4.96 µmol/L) | -0.01 mg/dL |
| Albumin | 6 g/dL | 5.48 mg/dL | |
| | (60 g/L) | (93.71 µmol/L) | -4.0% |
| Ascorbic acid | 5 mg/dL | 0.30 mg/dL | |
| | (284.1 µmol/L) | (5.13 µmol/L) | -0.02 mg/dL |
| Ascorbic acid | 5 mg/dL | 5.18 mg/dL | |
| | (284.1 µmol/L) | (88.58 µmol/L) | -1.0% |
| Carbenicillin | 3 mg/dL | 0.29 mg/dL | |
| | (79.3 µmol/L) | (4.96 µmol/L) | 0.00 mg/dL |
| Carbenicillin | 3 mg/dL | 5.23 mg/dL | 0.0% |
| Interferent | Interferent
Concentration
(SI) | Observed
Analyte (SI) | Observed
Bias from
Control |
| | (79.3 µmol/L) | (89.43 µmol/L) | |
| Cholesterol | 500 mg/dL
(12.9 mmol/L) | 0.30 mg/dL
(5.13 µmol/L) | 0.00 mg/dL |
| Cholesterol | 500 mg/dL
(12.9 mmol/L) | 5.52 mg/dL
(94.39 µmol/L) | -1.0% |
| Diazepam | 20 µg/mL
(70.2 µmol/L) | 0.27 mg/dL
(4.62 µmol/L) | 0.00 mg/dL |
| Diazepam | 20 µg/mL
(70.2 µmol/L) | 5.09 mg/dL
(87.04 µmol/L) | 0.0% |
| Eltrombopag | 25 µg/mL
(56.6 µmol/L) | 0.28 mg/dL
(4.79 µmol/L) | -0.01 mg/dL |
| Eltrombopag | 25 µg/mL
(56.6 µmol/L) | 5.03 mg/dL
(86.01 µmol/L) | -1.0% |
| Ethanol | 800 mg/dL
(173.5 mmol/L) | 0.28 mg/dL
(4.79 µmol/L) | 0.00 mg/dL |
| Ethanol | 800 mg/dL
(173.5 mmol/L) | 5.08 mg/dL
(86.87 µmol/L) | -1.0% |
| Ibuprofen | 50 mg/dL
(2427.2 µmol/L) | 0.29 mg/dL
(4.96 µmol/L) | -0.01 mg/dL |
| Ibuprofen | 50 mg/dL
(2427.2 µmol/L) | 5.18 mg/dL
(88.58 µmol/L) | -1.0% |
| IgG | 5 g/dL
(333.3 µmol/L) | 0.28 mg/dL
(4.79 µmol/L) | -0.01 mg/dL |
| IgG | 5 g/dL
(333.3 µmol/L) | 4.97 mg/dL
(84.99 µmol/L) | -1.0% |
| Levodopa | 300 µg/mL
(1522.8 µmol/L) | 0.27 mg/dL
(4.62 µmol/L) | 0.05mg/dL |
| Interferent | Interferent
Concentration
(SI) | Observed
Analyte (SI) | Observed
Bias from
Control |
| Levodopa | 300 µg/mL | 4.85 mg/dL | |
| | (1522.8 µmol/L) | (82.94 µmol/L) | 1.0% |
| Oxytetracycline | 50 mg/dL | 0.28 mg/dL | |
| | (1085.9 µmol/L) | (4.79 µmol/L) | 0.01 mg/dL |
| Oxytetracycline | 50 mg/dL | 5.19 mg/dL | |
| | (1085.9 µmol/L) | (88.75 µmol/L) | 0.0% |
| Phloroglucinol | 1500 ng/mL | 0.27 mg/dL | |
| | (11.9 µmol/L) | (4.62 µmol/L) | 0.01 mg/dL |
| Phloroglucinol | 1500 ng/mL | 5.26 mg/dL | |
| | (11.9 µmol/L) | (89.95 µmol/L) | -1.0% |
| Rheumatoid Factor | 510 IU/mL | 0.28 mg/dL | |
| | (510 IU/mL) | (4.79 µmol/L) | 0.00 mg/dL |
| Rheumatoid Factor | 510 IU/mL | 5.05 mg/dL | |
| | (510 IU/mL) | (86.36 µmol/L) | 0.0% |
| Rifampicin | 6 mg/dL | 0.30 mg/dL | |
| | (72.9 µmol/L) | (5.13 µmol/L) | 0.08 mg/dL |
| Rifampicin | 6 mg/dL | 5.24 mg/dL | |
| | (72.9 µmol/L) | (89.60 µmol/L) | 0.0% |
| Total Protein | 12 g/dL | 0.30 mg/dL | |
| | (120 g/L) | (5.13 µmol/L) | -0.01 mg/dL |
| Total Protein | 12 g/dL | 5.46 mg/dL | |
| | (120 g/L) | (93.37 µmol/L) | -8.0% |
13
14
Clinical Study 11.
Not applicable.
15
Expected Values 11.1
Siemens Healthineers has verified the reference interval for serum and plasma for the Atellica CH Diazo Direct Bilirubin assay, in accordance with CLSI Document EP28-A3c is ≤ 0.30 mg/dL (5.13 µmol/L).
12. Traceability
The Atellica CH D_DBil assay is traceable to internal reference standards manufactured by gravimetric methods
Clinical Cut-off 13.
Not applicable
Conclusion 14.
The results from the performance studies support that the Candidate Device, Atellica CH Diazo Direct Bilirubin (D_DBil) assay is substantially equivalent to the Predicate Device, Wako Direct Bilirubin V (K053132)