Atellica® CH Diazo Direct Bilirubin (D_DBil)

K223078 · Siemens Healthcare Diagnostics, Inc. · CIG · Jun 12, 2023 · Clinical Chemistry

Device Facts

• Record ID: K223078
• Device Name: Atellica® CH Diazo Direct Bilirubin (D_DBil)
• Applicant: Siemens Healthcare Diagnostics, Inc.
• Product Code: CIG · Clinical Chemistry
• Decision Date: Jun 12, 2023
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1110
• Device Class: Class 2

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-hematological, and metabolic disorders, including hepatitis and gall bladder block.

Device Story

Atellica® CH Diazo Direct Bilirubin (D_DBil) is an in vitro diagnostic assay for use on the Atellica® CH Analyzer. It utilizes a photometric diazo colorimetry method: direct bilirubin reacts with diazotized 2,4-dichloroaniline in an acidic solution to form a red azocompound. The analyzer measures absorbance at 545/658 nm to quantify direct bilirubin concentration. Operated by laboratory technicians in clinical settings, the device processes human serum or plasma samples. The output is a quantitative concentration value (mg/dL) provided to clinicians to assist in diagnosing and monitoring liver, hemolytic, and metabolic conditions. The assay is intended for prescription use.

Clinical Evidence

Bench testing only. Performance evaluated per CLSI guidelines (EP05-A3, EP07, EP09-A3, EP17-A2, EP28-A3c). Precision studies (N=80/225) showed CVs ≤ 3.2%. Method comparison against predicate (N=100) yielded r=0.993 and slope=0.95. LoQ=0.10 mg/dL. Interference testing confirmed no significant bias (≤10%) for common substances, though hemolysis causes significant negative interference.

Technological Characteristics

Photometric diazo colorimetry assay using 2,4-dichloroaniline. Reagents: two liquid, ready-to-use packs containing EDTA-Na2, NaCl, sulfamic acid, HCl, and Na-Nitrite. Measuring interval: 0.10–12.00 mg/dL. Traceability: internal reference standards via gravimetric methods. Analyzed on Atellica® CH Analyzer. No specific material standards (e.g., ASTM) cited.

Indications for Use

Indicated for in vitro diagnostic quantitative determination of direct bilirubin in human serum and plasma to aid in diagnosis and treatment of liver, hemolytic-hematological, and metabolic disorders (e.g., hepatitis, gall bladder block).

Regulatory Classification

Identification

A bilirubin (total or direct) test system is a device intended to measure the levels of bilirubin (total or direct) in plasma or serum. Measurements of the levels of bilirubin, an organic compound formed during the normal and abnormal distruction of red blood cells, if used in the diagnosis and treatment of liver, hemolytic hematological, and metabolic disorders, including hepatitis and gall bladder block.

Predicate Devices

• Wako Direct Bilirubin V (K053132)

Submission Summary (Full Text)

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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

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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 ([e-mail]) or phone [phone] 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

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## 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)

< | Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

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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<br>Regulatory Affairs Specialist |
|----------|----------------------------------------------------------------------------------------|
| Address: | Siemens Healthcare Diagnostics Inc.<br>P.O. Box 6101, M/S 514<br>Newark, DE 19714-1601 |
| Email: | [e-mail] |

### 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

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## 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<br>(K053132) |
| Intended Use | The Atellica CH Diazo Direct Bilirubin<br>(D_DBil) assay is for <i>in vitro</i> diagnostic use<br>in the quantitative determination of direct<br>bilirubin in human serum and plasma using<br>the Atellica CH Analyzer. Measurement of<br>direct bilirubin, an organic compound<br>formed during the normal and abnormal<br>destruction of red blood cells, is used in the<br>diagnosis and treatment of liver,<br>hemolytic-hematologcial, and metabolic<br>disorders, including hepatitis and gall<br>bladder block. | For <i>in vitro</i> diagnostic use in the<br>quantitative determination of<br>direct bilirubin in human serum or<br>plasma. Such measurements are<br>useful in the screening of liver<br>function disorders or in the<br>diagnosis of jaundice. |
| Sample Type | Human serum and plasma (lithium heparin,<br>sodium heparin, dipotassium EDTA) | Human Serum and plasma (Lithium<br>heparin) |
| Units of Measure | mg/dL | mg/dL |
| Assay Range / Measuring<br>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).<br>Direct bilirubin in presence of diazotized 2,4-<br>dichloroaniline forms a red colored<br>azocompound in acidic solution. Absorbance is<br>measured at 545/658 nm. | Bilirubin is oxidized by vanadate at about<br>pH 3 to produce biliverdin. In the presence<br>of detergent and vanadate, conjugated<br>(direct) bilirubin is oxidized. This oxidation<br>reaction causes a decrease in the optical<br>density of the yellow color, which is<br>specific to bilirubin. The decrease in<br>optical density at 451/545 nm is<br>proportional to the direct bilirubin<br>concentration in the sample. The<br>concentration is measured as an endpoint<br>reaction. |
| Traceability | Traceable to internal reference standards<br>manufactured by gravimetric methods | Traceable to reference method, which<br>uses reference materials from the National<br>Institute of Standards and Technology<br>(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:<br>23.5mL<br>EDTA-NA2(0.1 mmoll/L); NaCl (150mmol/L); sulfamic<br>acid (100 mmol/L) | 68 mL in 70-mLcontainers<br>Tartrate buffer, pH 2.9<br>(0.1 mol/L)Detergent |
| | Well 2 Reagent 1:<br>23.5mL<br>EDTA-NA2(0.1 mmoll/L); NaCl (150mmol/L); sulfamic<br>acid (100 mmol/L) | Direct Bilirubin Reagent 2:<br>25 mL in 70-mL containers<br>Phosphate buffer, pH 7.0(10<br>mmol/L)Sodium metavanadate (4 mmol/L) |
| | Pack 2: | |
| | Well 1 Reagent 2:<br>8.8mL<br>2,4-Dichloroaniline (5 mmol/L); HCl (920mmol/L);<br>EDTA-Na2 (0.13mmol/L); Na-Nitrite (0.5 mmol/L) | |
| | Well 2 Reagent 2:<br>8.8mL<br>2,4-Dichloroaniline (5 mmol/L); HCl (920mmol/L);<br>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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## 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<br>Type | N | Mean<br>(mg/dL) | Mean<br>(µmol/L) | SD<br>(mg/dL) | SD<br>(µmol/L) | CV<br>(%) | SD<br>(mg/dL) | SD<br>(µmol/L) | CV<br>(%) |
| 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<br>Type | N | Mean<br>mg/dL | Mean<br>µmol/L | Repeatability | | | Between-Day | | | Between-LOT | | | Between SYSTEM | | | Reproducibility | | |
|------------------|-----|---------------|----------------|---------------|--------------|---------|-------------|--------------|---------|-------------|--------------|---------|----------------|--------------|---------|-----------------|--------------|---------|
| | | | | SD<br>mg/dL | SD<br>µmol/L | %<br>CV | SD<br>mg/dL | SD<br>µmol/L | %<br>CV | SD<br>mg/dL | SD<br>µmol/L | %<br>CV | SD<br>mg/dL | SD<br>µmol/L | %<br>CV | SD<br>mg/dL | SD<br>µmol/L | %<br>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<br>Type | Comparison<br>Assay (x) | Regression Equation<br>mg/dL ( $\u03bcmol$ /L) | Sample Range<br>mg/dL ( $\u03bcmol$ /L) | N | r |
|------------------|----------------------------|------------------------------------------------|-----------------------------------------|-----|-------|
| Serum | Wako Direct<br>Bilirubin V | $y=0.95x-0.03mg/dL$ $(y=0.95x-.51)\u03bcmol/L$ | 0.10 - 11.10<br>(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<br>Type | Reference<br>Specimen | Regression Equation<br>mg/dL (µmol/L) | Sample Range<br>mg/dL (µmol/L) | N | r |
|--------------------------------|-----------------------|------------------------------------------|---------------------------------|----|-------|
| Plasma<br>(Lithium<br>heparin) | Serum | $y=1.00x - 0.02$<br>( $y=1.00x - 0.34$ ) | 0.10 - 10.27<br>(1.71 - 175.62) | 53 | 0.999 |
| Plasma<br>(Sodium<br>Heparin) | Serum | $y=0.98x + 0.00$<br>( $y=0.98 + 0.00$ ) | 0.10 - 10.27<br>(1.71 - 175.62) | 53 | 0.999 |
| Plasma<br>K2(EDTA) | Serum | $y=0.98x - 0.02$<br>( $y=0.98x - 0.34$ ) | 0.10 - 10.27<br>(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<br>Conventional Units (SI Units) | Analyte Concentration<br>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% |

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### 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.

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### 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<br>Concentration<br>(SI) | Observed<br>Analyte (SI) | Observed<br>Bias from<br>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<br>Concentration<br>(SI) | Observed<br>Analyte (SI) | Observed<br>Bias from<br>Control |
| | (79.3 µmol/L) | (89.43 µmol/L) | |
| Cholesterol | 500 mg/dL<br>(12.9 mmol/L) | 0.30 mg/dL<br>(5.13 µmol/L) | 0.00 mg/dL |
| Cholesterol | 500 mg/dL<br>(12.9 mmol/L) | 5.52 mg/dL<br>(94.39 µmol/L) | -1.0% |
| Diazepam | 20 µg/mL<br>(70.2 µmol/L) | 0.27 mg/dL<br>(4.62 µmol/L) | 0.00 mg/dL |
| Diazepam | 20 µg/mL<br>(70.2 µmol/L) | 5.09 mg/dL<br>(87.04 µmol/L) | 0.0% |
| Eltrombopag | 25 µg/mL<br>(56.6 µmol/L) | 0.28 mg/dL<br>(4.79 µmol/L) | -0.01 mg/dL |
| Eltrombopag | 25 µg/mL<br>(56.6 µmol/L) | 5.03 mg/dL<br>(86.01 µmol/L) | -1.0% |
| Ethanol | 800 mg/dL<br>(173.5 mmol/L) | 0.28 mg/dL<br>(4.79 µmol/L) | 0.00 mg/dL |
| Ethanol | 800 mg/dL<br>(173.5 mmol/L) | 5.08 mg/dL<br>(86.87 µmol/L) | -1.0% |
| Ibuprofen | 50 mg/dL<br>(2427.2 µmol/L) | 0.29 mg/dL<br>(4.96 µmol/L) | -0.01 mg/dL |
| Ibuprofen | 50 mg/dL<br>(2427.2 µmol/L) | 5.18 mg/dL<br>(88.58 µmol/L) | -1.0% |
| IgG | 5 g/dL<br>(333.3 µmol/L) | 0.28 mg/dL<br>(4.79 µmol/L) | -0.01 mg/dL |
| IgG | 5 g/dL<br>(333.3 µmol/L) | 4.97 mg/dL<br>(84.99 µmol/L) | -1.0% |
| Levodopa | 300 µg/mL<br>(1522.8 µmol/L) | 0.27 mg/dL<br>(4.62 µmol/L) | 0.05mg/dL |
| Interferent | Interferent<br>Concentration<br>(SI) | Observed<br>Analyte (SI) | Observed<br>Bias from<br>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)