Urea Nitrogen2

K203771 · Abbott Ireland Diagnostics Division · CDQ · May 31, 2022 · Clinical Chemistry

Device Facts

• Record ID: K203771
• Device Name: Urea Nitrogen2
• Applicant: Abbott Ireland Diagnostics Division
• Product Code: CDQ · Clinical Chemistry
• Decision Date: May 31, 2022
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1770
• Device Class: Class 2
• Attributes: Pediatric

Intended Use

The Urea Nitrogen2 assay is used for the quantitation of urea nitrogen in human serum, plasma, or urine on the ARCHITECT c System. The Urea Nitrogen2 assay is to be used as an aid in the diagnosis and treatment of certain renal and metabolic diseases.

Device Story

Urea Nitrogen2 assay is a quantitative photometric enzymatic test for use on the ARCHITECT c8000 System. Input: human serum, plasma, or urine samples. Principle: kinetic enzymatic reaction; urease hydrolyzes urea to ammonia and carbon dioxide; glutamate dehydrogenase (GLDH) converts ammonia and α-ketoglutarate to glutamate and water, oxidizing NADH to NAD. Output: decrease in absorbance at 340 nm proportional to urea concentration. Used in clinical laboratory settings by trained technicians. Results assist clinicians in diagnosing and monitoring renal and metabolic disease states.

Clinical Evidence

No clinical data. Performance established via bench testing, including precision (CLSI EP5-A3), linearity, interference (CLSI EP07), and method comparison against the predicate device (n=124 serum, n=121 urine). Correlation coefficients were 1.00 for both matrices.

Technological Characteristics

Enzymatic kinetic assay. Reagents: β-NADH, α-ketoglutaric acid, GLDH, urease. Form factor: reagent kit for ARCHITECT c8000 System. Traceability: NIST SRM 912b. Detection: photometric absorbance at 340 nm. Connectivity: integrated with ARCHITECT c8000 analyzer.

Indications for Use

Indicated for the quantitative measurement of urea nitrogen in human serum, plasma, or urine to aid in the diagnosis and treatment of renal and metabolic diseases in pediatric and adult populations.

Regulatory Classification

Identification

A urea nitrogen test system is a device intended to measure urea nitrogen (an end-product of nitrogen metabolism) in whole blood, serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of certain renal and metabolic diseases.

Predicate Devices

• Urea Nitrogen (k981918)

Submission Summary (Full Text)

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May 31, 2022

Abbott Ireland Diagnostics Division Tiffini Jenkins Regulatory Affairs Manager Lisnamuch Longford, Ireland

Re: K203771

Trade/Device Name: Urea Nitrogen2 Regulation Number: 21 CFR 862.1770 Regulation Name: Urea nitrogen test system Regulatory Class: Class II Product Code: CDO Dated: February 28, 2022 Received: March 2, 2022

Dear Tiffini Jenkins:

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.

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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 801); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email ([e-mail]) or phone [phone] or 301-796-7100).

Sincerely.

Marianela Perez-Torres, Ph.D. 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 Food and Drug Administration

Enclosure

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# Indications for Use

510(k) Number (if known) k203771

Device Name Urea Nitrogen2

Indications for Use (Describe)

The Urea Nitrogen2 assay is used for the quantitation of Urea Nitrogen in human serum, plasma, or urine on the ARCHITECT c System.

The Urea Nitrogen2 assay is to used as an aid in the diagnosis and treatment of certain renal and metabolic diseases.

| Type of Use (Select one or both, as applicable) | |
|-----------------------------------------------------------------------------------|----------------------------------------------------------------------------------|
| <div> <span> ☑ Prescription Use (Part 21 CFR 801 Subpart D) </span> </div> | <div> <span> ☐ Over-The-Counter Use (21 CFR 801 Subpart C) </span> </div> |

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### Section 5: 510(k) Summary (Summary of Safety and Effectiveness)

This summary of the 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

#### I. 510(k) Number

k203771

### II. Applicant Name

Abbott Ireland Diagnostics Division Lisnamuck, Longford, Longford, IE

Primary contact person for all communications:

Tiffini Jenkins, Regulatory Affairs Associate Director Abbott Diagnostics Division Phone [phone] Fax [phone]

Secondary contact person for all communications:

Magdalena Suszko, Regulatory Affairs Associate Director Abbott Diagnostics Division Phone [phone] Fax [phone]

Date Summary Prepared: May 24, 2022

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## III. Device Name

Urea Nitrogen2

## Reagents

Trade Name: Urea Nitrogen2 Device Classification: Class II Classification Name: Urease and Glutamic Dehydrogenase, Urea Nitrogen Governing Regulation Number: 21 CFR 862.1770 Product Code: CDQ

## IV. Predicate Device

Urea Nitrogen (k981918)

# V. Description of Device

# A. Principles of the Procedure

The Urea Nitrogen2 assay is an automated clinical chemistry assay. The Urea Nitrogen2 assay is a modification of a totally enzymatic procedure. * The test is performed as a kinetic assay in which the initial rate of the reaction is linear for a limited period of time. Urea in the sample is hydrolyzed by urease to ammonia and carbon dioxide. The second reaction, catalyzed by glutamate dehydrogenase (GLDH), converts ammonia and a-ketoglutarate to glutamate and water with the concurrent oxidation of reduced nicotinamide adenine dinucleotide (NADH) to nicotinamide adenine dinucleotide (NAD). Two moles of NADH are oxidized for each mole of urea present. The initial rate of decrease in absorbance at 340 nm is proportional to the urea concentration in the sample.

Methodology: Urease

^* Talke H, Schubert GE. Klinische Wochenschrift 1965;43:174.

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## B. Reagents

The various kit configurations of the Urea Nitrogen2 reagent kit are described below.

| | List Number | |
|----------------------------------|-------------|---------|
| | 04T1220 | 04T1230 |
| Tests per cartridge set | 350 | 1450 |
| Number of cartridge sets per kit | 4 | 4 |
| Tests per kit | 1400 | 5800 |
| Reagent 1 (R1) | 24.8 mL | 53.9 mL |
| Reagent 2 (R2) | 10.0 mL | 33.1 mL |

- Active ingredient: β-NADH (1.915 g/L). Preservative: sodium azide. R1
- R2 Active ingredients: α-ketoglutaric acid (13.149 g/L), GLDH (60.000 KU/L), and urease (10.000 KU/L). Preservative: sodium azide.

# VI. Intended Use of the Device

The Urea Nitrogen2 assay is used for the quantitation of urea nitrogen in human serum, plasma, or urine on the ARCHITECT c System.

The Urea Nitrogen2 assay is to be used as an aid in the diagnosis and treatment of certain renal and metabolic diseases.

# VII. Comparison of Technological Characteristics

The Urea Nitrogen2 assay (subject device) is an automated clinical chemistry assay for the quantitation of urea nitrogen in human serum, plasma, or urine on the ARCHITECT c System.

The similarities and differences between the subject assay and the predicate device are presented in the following table.

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| Characteristics | Subject Device<br>Urea Nitrogen2 (List No. 04T12) | Predicate Device<br>Urea Nitrogen (k981918;<br>List No. 7D75) |
|------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Platform | ARCHITECT c System | Same† |
| Intended Use<br>and Indications<br>for Use | The Urea Nitrogen2 assay is used for<br>the quantitation of urea nitrogen in<br>human serum, plasma, or urine on the<br>ARCHITECT c System.<br>The Urea Nitrogen2 assay is to be used<br>as an aid in the diagnosis and<br>treatment of certain renal and<br>metabolic diseases. | The Urea Nitrogen assay is used for<br>the quantitation of urea nitrogen in<br>human serum, plasma, or urine. |
| Methodology | Urease | Same |
| Specimen Type | Human serum, plasma, urine | Same |
| Assay Principle<br>/ Principle of<br>Procedure | The Urea Nitrogen2 assay is an<br>automated clinical chemistry assay.<br>The Urea Nitrogen2 assay is a<br>modification of a totally enzymatic<br>procedure.‡ The test is performed as a<br>kinetic assay in which the initial rate<br>of the reaction is linear for a limited<br>period of time. Urea in the sample is<br>hydrolyzed by urease to ammonia and<br>carbon dioxide. The second reaction,<br>catalyzed by glutamate dehydrogenase<br>(GLDH), converts ammonia and a-<br>ketoglutarate to glutamate and water<br>with the concurrent oxidation of<br>reduced nicotinamide adenine<br>dinucleotide (NADH) to nicotinamide<br>adenine dinucleotide (NAD). Two<br>moles of NADH are oxidized for each<br>mole of urea present. The initial rate of<br>decrease in absorbance at 340 nm is<br>proportional to the urea concentration<br>in the sample. | The Urea Nitrogen2 assay is a<br>modification of a totally enzymatic<br>procedure first described by Talke and<br>Schubert.‡ The test is performed as a<br>kinetic assay in which the initial rate<br>of the reaction is linear for a limited<br>period of time. Urea in the sample is<br>hydrolyzed by urease to ammonia and<br>carbon dioxide. The second reaction,<br>catalyzed by glutamate dehydrogenase<br>(GLD) converts ammonia and<br>α-ketoglutarate to glutamate and water<br>with the concurrent oxidation of<br>reduced nicotinamide adenine<br>dinucleotide (NADH) to nicotinamide<br>adenine dinucleotide (NAD). Two<br>moles of NADH are oxidized for each<br>mole of urea present. The initial rate<br>of decrease in absorbance at 340 nm is<br>proportional to the urea concentration<br>in the sample. |
| | | |
| Characteristics | Subject Device<br>Urea Nitrogen2 (List No. 04T12) | Predicate Device<br>Urea Nitrogen (k981918; List No.<br>7D75) |
| Standardization | NIST SRM 912b/Gravimetric | NIST SRM 912b/Differential Scanning<br>Calorimetry |
| Use of<br>Calibrators | Yes | Same |
| Use of Controls | Yes | Same |
| Assay Range | Serum/Plasma:<br>Analytical Measuring Interval:<br>2 — 125 mg/dL<br>Extended Measuring Interval:<br>125 – 625 mg/dL<br>Reportable Interval:<br>2 — 625 mg/dL<br>Urine: | Urea Nitrogen serum is linear from<br>2 to 125 mg/dL.<br>Urea Nitrogen urine is linear from<br>2 to 1991 mg/dL. |
| | Analytical Measuring Interval:<br>16 – 1991 mg/dL<br>Reportable Interval: 11 - 1991 mg/dL | |
| Precision | Serum/Plasma:<br>Samples with urea nitrogen<br>concentrations between 4 and<br>102 mg/dL were evaluated. The<br>samples demonstrated standard<br>deviations (SDs) \u2264 0.4 mg/dL and<br>% Coefficient of Variation (%CV)<br>\u22642.7%. | Serum/Plasma:<br>Samples with urea nitrogen<br>concentrations between 15.5 and<br>48.0 mg/dL demonstrated %CV values<br>ranging from 1.8 to 2.0%. |
| | Urine:<br>Samples with urea nitrogen<br>concentrations between 55 and<br>1605 mg/dL were evaluated. The<br>samples demonstrated SDs<br>\u2264 11.7 mg/dL and %CV \u2264 2.1%. | Urine:<br>Samples with urea nitrogen<br>concentrations between 504.8 and<br>896.4 mg/dL demonstrated %CV values<br>ranging from 3.1 to 3.8%. |
| | | |
| Characteristics | Subject Device<br>Urea Nitrogen2 (List No. 04T12) | Predicate Device<br>Urea Nitrogen (k981918; List No. 7D75) |
| Lower Limits of<br>Measurement | Serum/Plasma:<br>Limit of Blank: 1 mg/dL<br>Limit of Detection: 2 mg/dL<br>Limit of Quantitation: 2 mg/dL<br><br>Urine:<br>Limit of Blank: 6 mg/dL<br>Limit of Detection: 11 mg/dL<br>Limit of Quantitation: 16 mg/dL | Serum/Plasma:<br>Limit of Detection: 0.7 mg/dL<br>Limit of Quantitation: 1.4 mg/dL<br><br>Urine:<br>Limit of Detection: 15.0 mg/dL<br>Limit of Quantitation: 40.0 mg/dL |
| Tube Types | Serum:<br>- Serum tubes<br>- Serum separator tubes<br><br>Plasma:<br>- Lithium heparin tubes<br>- Lithium heparin separator tubes<br>- Sodium heparin tubes | Same |

Comparison of Subject Device (Urea Nitrogen2) to Predicate Device (Urea Nitrogen)

¹ In accordance with FDA Guidance Document "Data for Commercialization of Original Equipment Manufacturer, Secondary and Generic Reagent for Automated Analyzers", issued June 10, 1996, the assay equivalency study on ARCHITECT c System vs. the original platform, AEROSET, was performed and submitted under K980367/A004 in May 2002.

^‡ Talke H, Schubert GE. Klinische Wochenschrift 1965;43:174.

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## Comparison of Subject Device (Urea Nitrogen2) to Predicate Device (Urea Nitrogen) (Continued)

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### Comparison of Subject Device (Urea Nitrogen2) to Predicate Device (Urea Nitrogen) (Continued)

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## VIII. Summary of Nonclinical Performance

### A. Reportable Interval

Based on the limit of detection (LoD), limit of quantitation (LoQ), precision, and linearity, the ranges over which results can be reported are provided below according to the definitions from CLSI EP34, 1st ed. §

### Serum/Plasma

| | mg/dL |
|--------------------------------------|-----------|
| Analytical Measuring Interval (AMI)a | 2 - 125 |
| Extended Measuring Interval (EMI)b | 125 - 625 |
| Reportable Intervalc | 2 - 625 |

a AMI: The AMI extends from the LoQ to the upper limit of quantitation (ULoQ). This is determined by the range of values in mg/dL that demonstrated acceptable performance for linearity, imprecision, and bias.

b EMI: The EMI extends from the ULoQ to the ULoQ × sample dilution.

° The reportable interval extends from the LoD to the upper limit of the EMI.

#### Urine

| | mg/dL |
|--------------------------------------|-----------|
| Analytical Measuring Interval (AMI)a | 16 - 1991 |
| Reportable Intervalb | 11 - 1991 |

a AMI: The AMI extends from the LoQ to the upper limit of quantitation (ULoQ). This is determined by the range of values in mg/dL that demonstrated acceptable performance for linearity, imprecision, and bias.

b The reportable interval extends from the LoD to the upper limit of the AMI.

^े Clinical and Laboratory Standards Institute(CLS). Establishing and Verifying an Extended Measuring Interval Through Specinen Dilution and Spiking. 1st ed. CLSI Document EP34. Wayne, PA: CLSI; 2018.

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# B. Within-Laboratory Precision

### Serum/Plasma

A study was performed based on guidance from CLSI EP05-A3. ** Testing was conducted using 3 lots of the Urea Nitrogen2 reagent, 3 lots of the Consolidated Chemistry Calibrator, and 1 lot of commercially available controls and 3 instruments. Two controls and 3 human serum panels were tested in duplicate, twice per day on 20 days on 3 reagent lot/calibrator lot/instrument combinations, where a unique reagent lot and a unique calibrator lot is paired with 1 instrument. The performance from a representative combination is shown in the following table.

| | | | Within-Run<br>(Repeatability) | | Within-Laboratorya | |
|-----------------|----|-----------------|-------------------------------|-----|--------------------|--------------------|
| Sample | n | Mean<br>(mg/dL) | SD | %CV | SD<br>(Rangeb) | %CV<br>(Rangeb) |
| ControlLevel 1 | 80 | 15 | 0.3 | 2.1 | 0.4<br>(0.2 - 0.4) | 2.4<br>(1.6 - 2.4) |
| Control Level 2 | 80 | 49 | 0.5 | 1.1 | 0.8<br>(0.8 - 0.9) | 1.7<br>(1.6 - 1.7) |
| Panel A | 80 | 4 | 0.2 | 4.7 | 0.2<br>(0.0 - 0.2) | 4.7<br>(0.0 - 4.7) |
| Panel B | 80 | 22 | 0.3 | 1.1 | 0.5<br>(0.3 - 0.6) | 2.1<br>(1.4 - 2.7) |
| Panel C | 80 | 102 | 0.8 | 0.8 | 1.9<br>(1.2 - 2.5) | 1.8<br>(1.2 - 2.5) |

a Includes within-run, between-run, and between-day variability.

b Minimum and maximum SD or %CV a cross all rea gent lot and instrument combinations.

^** Clinical and Laboratory Standards Institute(CLSI). Evaluation of Quantitative Measurement Procedures; Approved Guideline-Third Edition. CLSI Document EP05-A3. Wayne, PA: CLSI; 2014.

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# Urine

A study was performed based on guidance from CLSI EP05-A3.tt Testing was conducted using 3 lots of the Urea Nitrogen2 reagent, 3 lots of the Consolidated Chemistry Calibrator, and 1 lot of commercially available controls and 3 instruments. Two controls and 3 human urine panels were tested in duplicate, twice per day on 20 days on 3 reagent lot/calibrator lot/instrument combinations, where a unique reagent lot and a unique calibrator lot is paired with 1 instrument. The performance from a representative combination is shown in the following table.

| | | | Within-Run<br>(Repeatability) | | Within-Laboratorya | |
|----------------|----|-----------------|-------------------------------|-----|-----------------------|---------------------|
| Sample | n | Mean<br>(mg/dL) | SD | %CV | SD<br>(Rangeb) | %CV<br>(Rangeb) |
| ControlLevel 1 | 80 | 447 | 3.7 | 0.8 | 7.1<br>(7.1 - 11.7) | 1.6<br>(1.6 - 2.6) |
| ControlLevel2 | 80 | 729 | 5.2 | 0.7 | 11.4<br>(11.2 - 15.4) | 1.6<br>(1.6 - 2.1) |
| Panel A | 80 | 55 | 2.2 | 4.1 | 2.7<br>(2.7 - 5.6) | 5.0<br>(5.0 - 10.3) |
| Panel B | 80 | 715 | 6.2 | 0.9 | 10.2<br>(10.2 - 15.1) | 1.4<br>(1.4 - 2.1) |
| Panel C | 80 | 1605 | 12.6 | 0.8 | 22.6<br>(22.6 - 27.8) | 1.4<br>(1.4 - 1.8) |

ª Includes within-run, between-run, and between-day variability.

b Minimum and maximum SD or %CV a cross all rea gent lot and instrument combinations.

^** Clinical and Laboratory Standards Institute (CLS). Evaluation of Quantitative Measurement Procedures; Approved Guideline-Third Edition. CLSI Document EP05-A3. Wayne, PA: CLSI; 2014.

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#### C. Accuracy

A study was performed to estimate the bias of the Urea Nitrogen2 assay relative to standard reference material (NIST SRM Standard 912b). Testing was conducted using 3 concentrations of standard across 3 lots of the Urea Nitrogen2 reagent, 2 lots of the Consolidated Chemistry Calibrator, and 1 instrument. The bias ranged from 1.6% to 4.2% for serum, and from -1.3% to 3.0% for urine.

### D. Lower Limits of Measurement

A study was performed based on guidance from CLSI EP17-A2. # Testing was conducted using 3 lots of the Urea Nitrogen2 reagent on each of 2 instruments over a minimum of 3 days. The results of the study support limit of blank (LoB), limit of detection (LoD), and limit of quantitation (LoQ) values as summarized below.

| | mg/dL |
|------|-------|
| LoBa | 1 |
| LoDb | 2 |
| LoQc | 2 |

#### Serum

#### Urine

| | mg/dL |
|------|-------|
| LoBa | 6 |
| LoDb | 11 |
| LoQc | 16 |

a The LoBrepresents the 95th percentile from n ≥ 60 replicates of zero-analyte samples.

b The LoD represents the lowest concentration at which the analyte can be detected with 95% probability based on n ≥ 60 replicates of low-analyte level samples.

6 The LoQ is defined as the lowest concentration at which a maximum allowable precision of 20% CV was met and was determined from n ≥ 60 replicates of low-analyte level samples.

^# Clinical and Laboratory Standards Institute(CLS). Evaluation of Detection Capability for Clinical Laboratory Measurent Procedures; Approved Guideline-Second Edition. CLSI Document EP 17-A2. Wayne, PA: CLSI; 2012.

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## E. Linearity

A study was performed based on guidance from CLSI EP06-A. § This assay is linear across the analytical measuring interval of 2 to 125 mg/dL for serum, and 16 to 1991 mg/dL for urine.

# F. Potentially Interfering Endogenous and Exogenous Substances

Serum/Plasma - Potentially Interfering Endogenous Substances

A study was performed based on guidance from CLSI EP07, 3rd ed. *** Each substance was tested at 2 levels of the analyte (approximately 10 mg/dL and 30 mg/dL).

No significant interference (interference within±10%) was observed at the following concentrations.

| Potentially Interfering Substance | Interferent Level |
|-----------------------------------|-------------------|
| Bilirubin - conjugated | 60 mg/dL |
| Bilirubin - unconjugated | 60 mg/dL |
| Hemoglobin | 2000 mg/dL |
| Total Protein | 10 g/dL |
| Triglycerides | 1500 mg/dL |

# Interference beyond ± 10% (based on 95% Confidence Intervals [CI]) was

observed at the concentrations and analyte levels shown below for the following substance.

| Potentially Interfering Substance | Interferent Level | Analyte Level | % Interference<br>(95% CI) |
|-----------------------------------|-------------------|---------------|----------------------------|
| Total Protein | 11 g/dL | 10 mg/dL | 11%<br>(9%, 14%) |

^\$\$ Clinical and Laboratory Standards Institute(CLS). Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline. CLSI Document EP06-A. Wayne, PA: CLSI; 2003.

^*** Clinical and Laboratory Standards Institute (CLSI). Interference Testing in Clinical Chemistry: 3rd ed. CLSI Guideline EP07. Wayne, PA: CLSI; 2018.

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# Serum/Plasma - Potentially Interfering Exogenous Substances

A study was performed based on guidance from CLSI EP07, 3rd ed.t*f Each substance was tested at 2 levels of the analyte (approximately 10 mg/dL and 30 mg/dL).

No significant interference (interference within±10%) was observed at the following concentrations.

| Potentially Interfering Substance | Interferent<br>Level | Potentially Interfering Substance | Interferent<br>Level |
|-----------------------------------------------------------|----------------------|-----------------------------------|----------------------|
| 3-methyl-(triazen-1-yl)imidazole-4-<br>carboxamide (MTIC) | 0.6 mg/L | Doxycycline | 20 mg/L |
| 4-methylamino-antipyrine | 3.3 mg/dL | Ibuprofen | 220 mg/L |
| 5-amino-4-imidazolecarboxamide<br>(AIC) | 3 mg/L | Levodopa | 8 mg/L |
| Acetaminophen | 160 mg/L | Methyldopa | 25 mg/L |
| Acetylcysteine | 150 mg/L | Metronidazole | 130 mg/L |
| Acetylsalicylic acid | 30 mg/L | Phenylbutazone | 330 mg/L |
| Ampicillin-Na | 80 mg/L | Rifampicin | 50 mg/L |
| Ascorbic acid | 60 mg/L | Sodium heparin | 4 U/mL |
| Biotin | 4250 ng/mL | Sulfapyridine | 300 mg/L |
| Ca-dobesilate | 60 mg/L | Sulfasalazine | 300 mg/L |
| Cefoxitin | 6287 mg/L | Temozolomide | 20 mg/L |
| Cyclosporine | 2 mg/L | Theophylline | 60 mg/L |
| Dipyrone (metamizole) | 45 mg/dL | | |

## Interference beyond ± 10% (based on 95% Confidence Intervals [CI]) was

observed at the concentrations and analyte levels shown below for the following substance.

| Potentially Interfering Substance | Interferent Level | Analyte Level | % Interference<br>(95% CI) |
|-----------------------------------|-------------------|---------------|----------------------------|
| Cefoxitin | 6600 mg/L | 10 mg/dL | 10%<br>(6%, 14%) |

^&quot;T" Clinical and Laboratory Standards Institute(CLS). Interference Testing in Clinical Chemistry. 3rd ed. CLSI Guideline EP07. Wayne, PA: CLSI; 2018.

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Urine - Potentially Interfering Endogenous Substances

A study was performed based on guidance from CLSI EP07, 3rd ed.## Each substance was tested at 2 levels of the analyte (approximately 700 mg/dL and 1500 mg/dL).

No significant interference (interference within±10%) was observed at the following concentrations.

| Potentially Interfering Substance | Interferent Level |
|-----------------------------------|-------------------|
| Ascorbate | 200 mg/dL |
| Glucose | 1000 mg/dL |
| Protein | 50 mg/dL |

Urine - Potentially Interfering Exogenous Substances

A study was performed based on guidance from CLSI EP07, 3rd ed. §§§ Each substance was tested at 2 levels of the analyte (approximately 700 mg/dL and 1500 mg/dL).

No significant interference (interference within±10%) was observed at the following concentrations.

| Potentially Interfering Substance | Interferent Level |
|-----------------------------------|-------------------|
| Acetaminophen | 16 mg/dL |
| Acetic acid (8.5N) | 6.25 mL/dL |
| Acetylcysteine | 15 mg/dL |
| Biotin | 4250 ng/mL |
| Boric acid | 250 mg/dL |
| Hydrochloric acid (6N) | 2.5 mL/dL |
| Ibuprofen | 22 mg/dL |
| Nitric acid (6N) | 5.0 mL/dL |
| Sodium carbonate | 1.25 g/dL |
| Sodium fluoride | 400 mg/dL |
| Sodium oxalate | 60 mg/dL |

^## Clinical and Laboratory Standards Institute(CLS). Interference Testing in Clinical Chemisstry. 3rd ed. CLSI Guideline EP07. Wayne, PA: CLSI: 2018.

SSS Clinical and Laboratory Standards Institute(CLS). Interference Testing in Clinical Chemistry. 3rd ed. CLSI Guideline EP07. Wayne, PA: CLSI; 2018.

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# G. Method Comparison

A study was performed based on guidance from CLSI EP09-A3 **** using the Passing-Bablok regression method.

| Urea Nitrogen2 vs Urea Nitrogen on the ARCHITECT c System | | | | | | |
|-----------------------------------------------------------|-------|-----|----------------------------|-----------|-------|------------------------|
| | Units | n | Correlation<br>Coefficient | Intercept | Slope | Concentration<br>Range |
| Serum | mg/dL | 124 | 1.00 | 0.74 | 1.02 | 4 - 123 |
| Urine | mg/dL | 121 | 1.00 | 8.95 | 1.03 | 41 - 1754 |

# H. Tube Type

A study was performed to evaluate the suitability of specific blood collection tube types for use with Urea Nitrogen2 assay. Samples were collected from a minimum of 40 donors and evaluated across tube types. The following blood collection tube types were determined to be acceptable for use with the Urea Nitrogen2 assay:

### Serum

- Serum tubes
- . Serum separator tubes

## Plasma

- Lithium heparin tubes .
- Lithium heparin separator tubes •
- Sodium heparin tubes •

^**** Samples; Approved Guideline-Third Edition. CLSI Document EP09-A3. Wayne, P A: CLSI; 2013.

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#### I. Dilution Verification

A study was performed to evaluate the performance of the Urea Nitrogen2 automated dilution protocol relative to the manual dilution procedure on the ARCHITECT c System. Five human serum samples were created by spiking urea stock solution into Serasub (a synthetic serum) to target concentration values of 150, 214, 278, 342, and 405 mg/dL. Each sample was divided into multiple aliquots. An aliquot of each sample was tested using the 1:5 automated dilution protocol on the ARCHITECT c System. The additional aliquots were divided such that 2 technicians each prepared 3 manual dilutions (1:5 dilution) of each sample using saline. Each sample preparation from a given technician was tested in a separate run.

The samples were tested in replicates of 5 using 1 lot each of reagents, calibrators, and controls on 2 instruments. The % difference values for the automated dilution protocol versus the manual dilution procedure ranged from -2.8% to -1.3% and therefore, demonstrated acceptable performance.

## IX. Summary of Clinical Performance

This section does not apply.

## X. Conclusion Drawn from Nonclinical Laboratory Studies

The similarities and differences between the subject device and predicate device are presented in Section 5-VII.

There is no known potential adverse effect to the operator when using this in vitro device according to the Urea Nitrogen2 reagent package insert instructions.