Atellica® CH Diazo Total Bilirubin (D_TBil)

K222104 · Siemens Healthcare Diagnostics, Inc. · CIG · Mar 20, 2023 · Clinical Chemistry

Device Facts

• Record ID: K222104
• Device Name: Atellica® CH Diazo Total Bilirubin (D_TBil)
• Applicant: Siemens Healthcare Diagnostics, Inc.
• Product Code: CIG · Clinical Chemistry
• Decision Date: Mar 20, 2023
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1110
• Device Class: Class 2
• Attributes: Pediatric

Intended Use

The Atellica® CH Diazo Total Bilirubin (D_TBil) assay is for in vitro diagnostic use in the quantitative determination of total bilirubin in adults and children (non-neonates) in human serum and plasma using the Atellica® CH Analyzer. 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.

Device Story

In vitro diagnostic assay for quantitative total bilirubin measurement in human serum/plasma; utilizes Atellica CH Analyzer. Principle: Diazo chemistry using 2,4-dichloroaniline (DCA) in acidic solution; forms red-colored azocompound measured photometrically at 545nm. Requires 6.0 µL sample. Used in clinical laboratory settings by trained personnel. Output: total bilirubin concentration (mg/dL). Assists clinicians in diagnosing/treating liver, hemolytic, hematological, and metabolic disorders. Performance validated via precision, linearity, and method comparison studies against predicate.

Clinical Evidence

Bench testing only. Precision/reproducibility evaluated per CLSI EP05-A3 (n=80/sample for precision; n=225/sample for reproducibility). Linearity (0.04-27.91 mg/dL) per CLSI EP06. Interference testing per CLSI EP07. Method comparison (n=103) vs. predicate showed Deming regression slope 1.02, intercept 0.08, r=0.997. Matrix comparison (n=57) confirmed equivalency across serum and heparin/EDTA plasma. LoB/LoD/LoQ validated per CLSI EP17-A2.

Technological Characteristics

Photometric diazo colorimetry assay. Reagents: 2,4-dichloroaniline, HCl, Na-Nitrite, phosphate buffer, NaCl, detergents. Measuring interval: 0.10-25.0 mg/dL. Traceable to NIST SRM 916. Analyzed on Atellica CH Analyzer. Software-controlled automated photometric measurement.

Indications for Use

Indicated for quantitative determination of total bilirubin in human serum and plasma for adults and children (non-neonates). Used 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

• Dimension TBI Flex reagent cartridge (K060628)

Submission Summary (Full Text)

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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 is in blue and includes the letters "FDA" followed by the words "U.S. Food & Drug Administration".

March 20, 2023

Siemens Healthcare Diagnostics Inc. Anthony Calabro Regulatory Affairs Specialist 500 GBC Drive M/S 514, P.O. Box 6101 Newark, DE 19714

Re: K222104

Trade/Device Name: Atellica® CH Diazo Total Bilirubin (D_TBil) Regulation Number: 21 CFR 862.1110 Regulation Name: Bilirubin (Total Or Direct) Test System Regulatory Class: Class II Product Code: CIG Dated: December 22, 2022 Received: December 22, 2022

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

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statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about 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 | Digitally signed by<br>Paula Caposino -S |
|--------------------------------------------------|------------------------------------------|
| Caposino -S Date: 2023.03.20<br>16:51:17 -04'00' | |

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)

K222104 Device Name

Atellica® CH Diazo Total Bilirubin (D TBil)

### Indications for Use (Describe)

The Atellica® CH Diazo Total Bilirubin (D TBil) assay is for in vitro diagnostic use in the quantitative determination of total bilirubin in adults and children (non-neonates) in human serum and plasma using the Atellica® CH Analyzer. 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.

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: K222104

## 1. Date Prepared

December 14, 2022

## 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 Total Bilirubin (D_TBil) assay

Trade Name: Atellica® CH Diazo Total Bilirubin (D TBil) 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: Dimension TBI Flex reagent cartridge 510(k) Number: K060628

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## 5. Intended Use / Indications For Use

The Atellica® CH Diazo Total Bilirubin (D_TBil) assay is for in vitro diagnostic use in the quantitative determination of total bilirubin in adults and children (non-neonates) in human serum and plasma using the Atellica® CHAnalyzer. 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.

Special Conditions for Use Statement: For Prescription Use Only

## 6. Device Description

Atellica CH Diazo Total 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. A specific mixture of detergents enables the determination of the total bilirubin.

## 7. Purpose of Submission

The purpose of this submission is a premarket notification for a new device: Atellica CH Diazo Total Bilirubin (D TBil) assay

## 8. Comparison of Candidate Device and Predicate Device

The table below describes the similarities and differences between the Atellica CH Diazo Total Bilirubin assay (Candidate Device) and the Dimension TBI Flex reagent cartridge (Predicate Device).

Substantial equivalence was demonstrated by testing several performance characteristics including measuring interval, expected values, reference interval, precision, method comparison, interference, and specimen equivalence by method comparison.

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| Feature | Candidate Device | Predicate Device |
|-------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | Atellica® CH Diazo Total Bilirubin<br>(D_TBil) | Dimension TBI Flex reagent<br>cartridge<br>(k060628) |
| Intended Use | The Atellica® CH Diazo Total Bilirubin<br>(D_TBil) assay is for in vitro<br>diagnostic use in the<br>quantitative determination of total<br>bilirubin in adults and children (non-<br>neonates) in human serum and<br>plasma using the Atellica® CH<br>Analyzer. Measurement of total<br>bilirubin, an organic compound<br>formed during the normal and<br>abnormal destruction of red blood<br>cells, is used in the diagnosis and<br>treatment of liver,<br>hemolytic hematological, and<br>metabolic disorders, including<br>hepatitis and gall bladder block. | The TBI method for the Dimension®<br>clinical chemistry system is an in vitro<br>diagnostic test intended to<br>quantitatively measure total bilirubin<br>in human serum and plasma.<br>Measurements of total bilirubin are<br>used in the diagnosis and treatment of<br>liver, hemolytic, hematological, and<br>metabolic disorders, including<br>hepatitis and gallbladder disease. |
| Sample Type | Human serum and plasma (lithium heparin,<br>sodium heparin, dipotassium EDTA) | Human Serum and plasma (Lithium<br>heparin, EDTA) |
| Units of Measure | mg/dL | mg/dL |
| Assay Range / Measuring<br>Interval | 0.10 mg/dL - 25.0 mg/dL | 0.10 mg/dL - 25.0 mg/dL |
| Expected Values | 0.3mg/dL - 1.2 mg/dL | 0.2 mg/dL - 1.0mg/dL |

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| Feature | Candidate Device | Predicate Device |
|-----------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | Atellica® CH Diazo Total Bilirubin (D_TBil) | Dimension TBI Flex reagent cartridge<br>(k060628) |
| 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. A specific<br>mixture of detergents enables the determination<br>of the total bilirubin. | Diazotized sulfanilic acid is formed by<br>combining sodium nitrite and sulfanilic<br>acid at low pH. Bilirubin<br>(unconjugated) in the sample is<br>solubilized by dilution in a mixture of<br>caffeine/benzoate/acetate/EDTA.<br>Upon addition of the diazotized<br>sulfanilic acid, the solubilized bilirubin<br>including conjugated bilirubins (mono<br>and diglucoronides) and the delta<br>form4 (biliprotein-bilirubin covalently<br>bound to albumin) is converted to<br>diazo-bilirubin, a red chromophore<br>representing the total bilirubin which<br>absorbs at 540 nm and is measured<br>using a bichromatic (540, 700 nm)<br>endpoint technique. A sample blank<br>correction is used. |
| Traceability | NIST Standard Reference Material 916 | Same |
| Calibration | Single level calibration | Multi-Level Calibration |
| Calibrators | Atellica CH Bilirubin Calibrator (BILI CAL) | Dimension TBI/DBI Calibrator |
| Reagents | Two liquid reagents, ready to use | Ready-for-use liquid reagents |
| Feature | Candidate Device | Predicate Device |
| | Atellica® CH Diazo Total Bilirubin (D_TBil) | Dimension TBI Flex reagent cartridge (k060628) |
| Composition | Pack 1:<br>Well 1 Reagent 1:<br>23.5mL<br>Phosphate buffer (50mmol/L) ; NaCl (150mmol/L)<br>Well 2 Reagent 1:<br>23.5mL<br>Phosphate buffer (50mmol/L) ; NaCl (150mmol/L)<br>Pack 2:<br>Well 1 Reagent 2:<br>8.8mL<br>2,4-Dichloroaniline (5 mmol/L); HCl (130 mmol/L); Na-Nitrite (0.5 mmol/L)<br>Well 2 Reagent 2:<br>8.8mL<br>2,4-Dichloroaniline (5 mmol/L); HCl (130 mmol/L); Na-Nitrite (0.5 mmol/L) | Multi-Well liquid reagent cartridge that contains:<br>Wells 1, 4-6: Acetate Buffer, Caffeine (168 mM), Sodium Benzoate (338 mM), Disodium EDTA (2.57mM)<br>Well 2: Sulfanilic acid (25.89 mM), Hydrochloric acid (132 mM),<br>Well 3: Sodium Nitrite (72.5 mM) |
| Interferences | Hemoglobin:<br>No Interference ≤ 1000 mg/dL<br>Lipemia:<br>No Interference ≤ 1000 mg/dL | Hemoglobin:<br>No Interference ≤ 1000 mg/dL<br>Lipemia:<br>No Interference ≤ 600mg/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) EPO9-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; A Report (CLSI EP32-R)

- Supplemental tables for Interference Testing in Clinical Chemistry (CLSI EP37-ED1)
• Evaluation of the Linearity of Quantitative Measurement Procedures -200 Edition (CLSI EP06 ED2)

### Performance Characteristics for Atellica® CH Diazo Total Bilirubin (D_TBil) 10.

#### 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 total 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 total bilirubin that met the required analyte level but did not reach 20% deviation The assay is designed to have an 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 | 0.01 |
| | 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.

| Specimen<br>Type | N | Mean | | Repeatability | | | Within-Lab | | |
|------------------|----|---------------|----------------|---------------|--------------|-----|-------------|--------------|-----|
| | | Mean<br>mg/dL | Mean<br>μmol/L | SD<br>mg/dL | SD<br>μmol/L | %CV | SD<br>mg/dL | SD<br>μmol/L | %CV |
| Serum 1 | 80 | 1.02 | 17.44 | 0.015 | 0.257 | 1.5 | 0.034 | 0.581 | 3.3 |
| Serum 2 | 80 | 13.40 | 229.14 | 0.053 | 0.906 | 0.4 | 0.140 | 2.394 | 1.0 |
| Serum 3 | 80 | 22.39 | 382.87 | 0.067 | 1.146 | 0.3 | 0.189 | 3.232 | 0.8 |

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#### 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.

| Sample ID | 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 |
| 1 | Serum | 225 | 1.03 | 17.61 | 0.012 | 0.205 | 1.2 | 0.009 | 0.154 | 0.9 | 0.013 | 0.222 | 1.3 | 0.011 | 0.188 | 1.1 | 0.023 | 0.393 | 2.2 |
| 2 | Serum | 225 | 13.24 | 226.40 | 0.037 | 0.633 | 0.3 | 0.062 | 1.060 | 0.5 | 0.028 | 0.479 | 0.2 | 0.047 | 0.804 | 0.4 | 0.091 | 1.556 | 0.7 |
| 3 | Serum | 225 | 22.14 | 378.59 | 0.057 | 0.975 | 0.3 | 0.106 | 1.813 | 0.5 | 0.053 | 0.906 | 0.2 | 0.063 | 1.077 | 0.3 | 0.146 | 2.497 | 0.7 |

#### 10.4 Assay Comparison

The Atellica CH Diazo Total Bilirubin (D_TBil) assay was designed to have correlation coefficient of ≥ 0.950 and a slope of 1.00 ± 0.10 compared to the Dimension TBI assay. The following results were obtained.

| Specimen<br>Type | Comparison<br>Assay (x) | Regression Equation | Sample Range<br>mg/dL<br>(μmol/L) | N | r |
|------------------|-------------------------|-------------------------------------------|-----------------------------------|-----|-------|
| Serum | Dimension<br>TBI | y=1.02x+0.08mg/dL<br>(y=1.02x+1.37μmol/L) | 0.14-22.55<br>(2.39-385.61) | 103 | 0.997 |

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#### 10.5 Specimen Equivalency

The specimen equivalency was determined using the Demming regression model in accordance with CLSI Document EP90c. The following results were obtained:

| Specimen<br>Type | Comparison<br>Assay (x) | Regression Equation<br>(μmol/L) | Sample Range mg/dL<br>(µmol/L) | N | r |
|--------------------------------|-------------------------|-------------------------------------------------|--------------------------------------------|----|-------|
| Plasma<br>(Lithium<br>heparin) | Serum | y=0.98x + 0.05 mg/dL<br>(y=0.98X + 0.86 µmol/L) | 0.24-22.61 mg/dL<br>(4.10 – 386.63 µmol/L) | 57 | 0.997 |
| Plasma<br>(Sodium<br>Heparin) | Serum | y=1.00x + 0.02 mg/dL<br>(y=1.00X + 0.34 µmol/L) | 0.24-22.61 mg/dL<br>(4.10 – 386.63 µmol/L) | 57 | 0.998 |
| Plasma<br>(K2 EDTA) | Serum | y=0.99x + 0.03 mg/dL<br>(y=0.99X + 0.51 µmol/L) | 0.24-22.61 mg/dL<br>(4.10 – 386.63 µmol/L) | 57 | 0.998 |

#### 10.6 Interferences

### 10.6.1 Hemolysis, Icterus, and Lipemia (HIL)

The Atellica CH Diazo Total Bilirubin (D_TBil) assay is designed to have ≤ 10% interference from hemoglobin, 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 | Interferent<br>Concentration (SI) | Observed<br>Analyte<br>mg/dL<br>(µmol/L) | Observed %<br>Bias from<br>Control |
|-------------------------------------------------|-----------------------------------|------------------------------------------|------------------------------------|
| Hemoglobin | 1000 mg/dL<br>(10.0 g/L) | 1.08<br>(18.47) | -9.3 |
| Hemoglobin | 1000 mg/dL<br>(10.0 g/L) | 13.86<br>(237.00) | -7.1 |
| Lipemia (from High<br>Fraction<br>Triglyceride) | 1000 mg/dL<br>(10.0 g/L) | 0.90<br>(15.39) | -7.8 |
| Lipemia (from High<br>Fraction<br>Triglyceride) | 1000 mg/dL<br>(10.0 g/L) | 12.94<br>(221.27) | 0.5 |

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### 10.6.2 Non-interfering Substances

The following substances do not interfere with Atellica CH Diazo Total Bilirubin (D_TBil) 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<br>mg/dL<br>(µmol/L) | Acceptance<br>Criteria | Observed<br>% Bias | Acceptance<br>Criteria |
|--------------------------------|--------------------------------------|------------------------------------------|------------------------|--------------------|------------------------|
| Acetaminophen | 20 mg/dL<br>1323.1 µmol/L | 1.04<br>(17.78) | 1.00 mg/dL<br>± 15.0% | -1.9 | ≤10.0% |
| Acetaminophen | 20 mg/dL<br>1323.1 µmol/L | 13.85<br>(236.84) | 14.00 mg/dL<br>± 15.0% | -0.4 | ≤10.0% |
| Carbenicillin | 3 mg/dL<br>79.3 µmol/L | 1.01<br>(17.27) | 1.00 mg/dL<br>± 15.0% | 2.0 | ≤10.0% |
| Carbenicillin | 3 mg/dL<br>79.3 µmol/L | 13.82<br>(236.32) | 14.00 mg/dL<br>± 15.0% | 0.1 | ≤10.0% |
| Ascorbic acid | 5 mg/dL<br>284.1 µmol/L | 1.01<br>(17.27) | 1.00 mg/dL<br>± 15.0% | -2.0 | ≤10.0% |
| Ascorbic acid | 5 mg/dL<br>284.1 µmol/L | 13.51<br>(231.02) | 14.00 mg/dL<br>± 15.0% | -0.4 | ≤10.0% |
| Acetylsalicylic acid | 100 mg/dL<br>5555.6 µmol/L | 1.01<br>(17.27) | 1.00 mg/dL<br>± 15.0% | 0.0 | ≤10.0% |
| Acetylsalicylic acid | 100 mg/dL<br>5555.6 µmol/L | 13.62<br>(232.90) | 14.00 mg/dL<br>± 15.0% | 0.1 | ≤10.0% |
| Ibuprofen | 50 mg/dL | 1.01 | 1.00 mg/dL | -5.0 | ≤10.0% |
| Interferent | Interferent<br>Concentration<br>(SI) | Observed<br>Analyte<br>mg/dL<br>(µmol/L) | Acceptance<br>Criteria | Observed<br>% Bias | Acceptance<br>Criteria |
| Ibuprofen | 2427.2 µmol/L | (17.27) | ± 15.0% | | |
| | 50 mg/dL | 13.50 | 14.00 mg/dL | | |
| Ibuprofen | 2427.2 µmol/L | (230.85) | ± 15.0% | | |
| | Rifampicin | 6 mg/dL | 1.02 | | |
| 72.9 µmol/L | | (17.44) | ± 15.0% | | |
| Rifampicin | 6 mg/dL | 13.66 | 14.00 mg/dL | -3.5 | ≤10.0% |
| | 72.9 µmol/L | (233.59) | ± 15.0% | | |
| Diazepam | 20 µg/mL | 1.03 | 1.00 mg/dL | -1.9 | ≤10.0% |
| | 70.2 µmol/L | (17.61) | ± 15.0% | | |
| Diazepam | 20 µg/mL | 13.81 | 14.00 mg/dL | 0.2 | ≤10.0% |
| | 70.2 µmol/L | (236.15) | ± 15.0% | | |
| Ethanol | 800 mg/dL | 1.04 | 1.00 mg/dL | -1.9 | ≤10.0% |
| | 173.5 mmol/L | (17.78) | ± 15.0% | | |
| Ethanol | 800 mg/dL | 13.78 | 14.00 mg/dL | -0.7 | ≤10.0% |
| | 173.5 mmol/L | (235.64) | ± 15.0% | | |
| Eltrombopag | 25 µg/mL | 0.99 | 1.00 mg/dL | 0.0 | ≤10.0% |
| | 56.6 µmol/L | (16.93) | ± 15.0% | | |
| Eltrombopag | 25 µg/mL | 13.67 | 14.00 mg/dL | 0.3 | ≤10.0% |
| | 56.6 µmol/L | (233.76) | ± 15.0% | | |
| Cholesterol | 500 mg/dL | 1.03 | 1.00 mg/dL | -1.0 | ≤10.0% |
| | 12.9 mmol/L | (17.61) | ± 15.0% | | |
| Cholesterol | 500 mg/dL | 13.69 | 14.00 mg/dL | -0.7 | ≤10.0% |
| | 12.9 mmol/L | (234.10) | ± 15.0% | | |
| Interferent | Interferent<br>Concentration<br>(SI) | Observed<br>Analyte<br>mg/dL<br>(µmol/L) | Acceptance<br>Criteria | Observed<br>% Bias | Acceptance<br>Criteria |
| Phenazopyridine HCl | 80 µg/mL | 0.98 | 1.00 mg/dL | 0.0 | ≤10.0% |
| | 32.04 µmol/L | (16.76) | ± 15.0% | | |
| Phenazopyridine HCl | 80 µg/mL | 12.99 | 14.00 mg/dL | 0.5 | ≤10.0% |
| | 32.04 µmol/L | (222.13) | ± 15.0% | | |
| Phloroglucinol | 250 ng/mL | 1.01 | 1.00 mg/dL | 0.0 | ≤10.0% |
| | 2 µmol/L | (17.27) | ± 15.0% | | |
| Phloroglucinol | 250 ng/mL | 13.77 | 14.00 mg/dL | -0.9 | ≤10.0% |
| | 2 µmol/L | (235.47) | ± 15.0% | | |
| Cyanokit<br>(Hydroxocobalamin) | 40 µg/mL | 1.01 | 1.00 mg/dL | -4.0 | ≤10.0% |
| | 29.7 µmol/L | (17.27) | ± 15% | | |
| Cyanokit<br>(Hydroxocobalamin) | 40 µg/mL | 13.58 | 14.00 mg/dL | -2.0 | ≤10.0% |
| | 29.7 µmol/L | (232.22) | ± 15.0% | | |
| Levodopa | 225 µg/mL | 0.93 | 1.00 mg/dL | 8.6 | ≤10.0% |
| | 1142.1 µmol/L | (15.90) | ± 15.0% | | |
| Levodopa | 300 µg/mL | 12.82 | 14.00 mg/dL | 0.5 | ≤10.0% |
| | 1522.8 µmol/L | (219.22) | ± 15% | | |
| IgG | 5 g/dL | 0.96 | 1.00 mg/dL | -1.0 | ≤10.0% |
| | 333.3 µmol/L | (16.42) | ± 15.0% | | |
| IgG | 5 g/dL | 12.90 | 14.00 mg/dL | -0.2 | ≤10.0% |
| | 333.3 µmol/L | (220.59) | ± 15.0% | | |
| Indican | 1.5 mg/dL | 0.94 | 1.00 mg/dL | 7.9 | ≤10.0% |
| | 59.7 µmol/L | (16.07) | ± 15.0% | | |
| Indican | 31.3 mg/dL | 13.59 | 14.00 mg/dL | 8.6 | ≤10.0% |
| Interferent | Interferent<br>Concentration<br>(SI) | Observed<br>Analyte<br>mg/dL<br>(µmol/L) | Acceptance<br>Criteria | Observed<br>% Bias | Acceptance<br>Criteria |
| | | | | | |
| | 1245.5 µmol/L | (232.39) | ± 15.0% | | |

{13}------------------------------------------------

{14}------------------------------------------------

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### Clinical Study 11.

Not applicable.

#### 11.1 Expected Values

Siemens Healthineers has verified the reference interval for serum and plasma for the Atellica CH Diazo Total Bilirubin assay, in accordance with CLSI Document EP28-A3c is 0.3 - 1.2mg/dL (5.13 - 20.52 µmol/L)

### Traceability 12.

The assay is traceable to the NIST Standard Reference Material 916.

### Clinical Cut-off 13.

Not applicable

### Conclusion 14.

The results from the performance studies support that the Candidate Device, Atellica CH Diazo Total Bilirubin (D_TBil) assay is substantially equivalent to the Predicate Device, Dimension TBI assay (K060628)