Calcium2

K244042 · Abbott Ireland · CJY · Feb 10, 2025 · Clinical Chemistry

Device Facts

• Record ID: K244042
• Device Name: Calcium2
• Applicant: Abbott Ireland
• Product Code: CJY · Clinical Chemistry
• Decision Date: Feb 10, 2025
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1145
• Device Class: Class 2

Intended Use

The Calcium2 assay is used for the quantitation of calcium in human serum, plasma, or urine on the ARCHITECT c System. Calcium measurements are used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany (intermittent muscular contractions or spasms).

Device Story

Calcium2 is an automated clinical chemistry assay for the ARCHITECT c System; measures calcium concentration in human serum, plasma, or urine. Principle of operation: Arsenazo III dye reacts with calcium in an acid solution to form a blue-purple complex; color intensity measured at 660 nm is proportional to calcium concentration. Used in clinical laboratories by technicians; results are reviewed by physicians to assist in diagnosing and managing parathyroid, bone, and renal diseases, and tetany. Provides quantitative calcium levels to support clinical decision-making.

Clinical Evidence

Bench testing only. Performance validated on ARCHITECT c8000 System. Studies included precision (within-run, within-lab, reproducibility per CLSI EP05-A3), accuracy (bias vs NIST SRM 956d), linearity (CLSI EP06), and interference testing (CLSI EP07). Method comparison (CLSI EP09c) against predicate showed correlation coefficient of 1.00 for both serum (n=120) and urine (n=112). LoB, LoD, and LoQ established per CLSI EP17-A2.

Technological Characteristics

Automated clinical chemistry assay using Arsenazo III dye. Reagent contains Arsenazo III (0.932 g/L) and sodium azide preservative. Operates on ARCHITECT c System. Serum/plasma AMI: 2.0–24.0 mg/dL; Urine AMI: 2.0–24.0 mg/dL with EMI up to 96.0 mg/dL. Traceable to NIST SRM 956. Connectivity via ARCHITECT c8000 platform.

Indications for Use

Indicated for the quantitation of calcium in human serum, plasma, or urine to aid in the diagnosis and treatment of parathyroid disease, bone diseases, chronic renal disease, and tetany.

Regulatory Classification

Identification

A calcium test system is a device intended to measure the total calcium level in serum. Calcium measurements are used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany (intermittent muscular contractions or spasms).

Submission Summary (Full Text)

{0}------------------------------------------------

Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the FDA logo is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

February 10, 2025

Abbott Ireland Cherie Lipowsky Regulatory Affairs Manager Diagnostic Divison Lisnamuck, Longford Ireland

Re: K244042

Trade/Device Name: Calcium2 Regulation Number: 21 CFR 862.1145 Regulation Name: Calcium test system Regulatory Class: Class II Product Code: CJY Dated: December 30, 2024 Received: December 30, 2024

Dear Cherie Lipowsky:

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 (the 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 available 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.

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device"

{1}------------------------------------------------

(https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30. Design controls; 21 CFR 820.90. Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review. the OS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-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 Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rue"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-device-advicecomprehensive-regulatory-assistance/unique-device-identification-system-udi-system.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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.

{2}------------------------------------------------

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,

## Paula V. Caposino -S

Paula Caposino, Ph.D. Deputy Division 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

{3}------------------------------------------------

## Indications for Use

Submission Number (if known)

K244042

Device Name

Calcium2

Indications for Use (Describe)

The Calcium2 assay is used for the quantitation of calcium in human serum, plasma, or urine on the ARCHITECT c System.

Calcium measurements are used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany (intermittent muscular contractions or spasms).

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)

#### CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

#### *DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW *

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

> Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

{4}------------------------------------------------

## Administrative Documentation - 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 the Federal Food, Drug, and Cosmetic Act, and 21 CFR §807.92.

#### 510(k) Number: K244042

#### I. Applicant Name

Abbott Ireland Diagnostics Division Lisnamuck, Longford, Co. Longford, Ireland

Primary contact person for all communications:

Cherie Lipowsky, Regulatory Affairs Manager Abbott Diagnostics Division Phone: [phone] Fax: [phone] Email: cherie.lipowsky(@abbott.com

Secondary contact person for all communications:

Jacob Richards, Associate Director of Regulatory Affairs Abbott Diagnostics Division Phone: [phone] Fax: [phone] Email: jacob.richards(@abbott.com

Date Summary Prepared: February 07, 2025

{5}------------------------------------------------

#### II. Subject Device

Trade Name: Calcium2

Device Classification: Class II Classification Name: Calcium Test System Regulation Number: 21 CFR §862.1145 Product Code: CJY

## III. Predicate Device

Abbott Clinical Chemistry Architect/Aeroset Calcium; k062855

### IV. Description of Device

### A. Principles of the Procedure

The Calcium2 assay is an automated clinical chemistry assay. Arsenazo III dye reacts with calcium in an acid solution to form a blue-purplex. The color developed is measured at 660 nm and is proportional to the calcium concentration in the sample.

Methodology: Arsenazo III

## B. Reagent

The configurations of the Calcium2 reagent kits are described below.

| | List Number | |
|------------------------------|-------------|---------|
| | 04S9120 | 04S9130 |
| Tests per cartridge | 300 | 1,350 |
| Number of cartridges per kit | 4 | 4 |
| Tests per kit | 1,200 | 5,400 |
| Reagent 1 (R1) | 22.9 mL | 91.8 mL |

R1: Active ingredient: Arsenazo III 0.932 g/L. Preservative: sodium azide.

{6}------------------------------------------------

## V. Intended Use of the Device

The Calcium2 assay is used for the quantitation of calcium in human serum, plasma, or urine on the ARCHITECT c System.

Calcium measurements are used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany (intermittent muscular contractions or spasms).

#### VI. Comparison of Technological Characteristics

The Calcium2 assay (subject device) is an automated clinical chemistry assay for the quantitation of calcium in human serum, plasma, or urine on the ARCHITECT c System.

The similarities and differences between the subject device and the predicate device are presented in the Assay Similarities (Table VI.1) and Assay Differences (Table VI.2), respectively.

{7}------------------------------------------------

# Table VI.1
Assay Similarities

| Characteristics | Subject Device<br>Calcium2 (List Number [LN] 04S91)<br>(K244042) | Predicate Device<br>Abbott Clinical Chemistry Architect/Aeroset<br>Calcium (LN 3L79)<br>(k062855) |
|-----------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use and<br>Indications for Use | The Calcium2 assay is used for the quantitation of<br>calcium in human serum, plasma, or urine on the<br>ARCHITECT c System.<br>Calcium measurements are used in the diagnosis and<br>treatment of parathyroid disease, a variety of bone<br>diseases, chronic renal disease and tetany (intermittent<br>muscular contractions or spasms). | The Calcium assay is used for the quantitation of calcium in<br>human serum, plasma, or urine.<br>Calcium measurements are used in the diagnosis and<br>treatment of parathyroid disease, a variety of bone diseases,<br>chronic renal disease and tetany (intermittent muscular<br>contractions or spasms). |
| Methodology | Arsenazo III | Same |
| Specimen Type | Human serum, plasma, or urine | Same |
| Assay Principle/<br>Principle of<br>Procedure | The Calcium2 assay is an automated clinical chemistry<br>assay. Arsenazo III dye reacts with calcium in an acid<br>solution to form a blue-purple complex. The color<br>developed is measured at 660 nm and is proportional to<br>the calcium concentration in the sample. | Same |
| Use of Calibrators | Yes | Same |
| Use of Controls | Yes | Same |
| Traceability | NIST SRM 956 | Same |
| Characteristics | Subject Device<br>Calcium2 (List Number [LN] 04S91)<br>(K244042) | Predicate Device<br>Abbott Clinical Chemistry Architect/Aeroset<br>Calcium (LN 3L79)<br>(k062855) |
| Platform | ARCHITECT c8000 System | AEROSET and ARCHITECT c8000 System |
| Assay Range | Serum/Plasma:<br>Analytical Measuring Interval (AMI):<br>2.0–24.0 mg/dL<br>Reportable Interval:<br>0.2–24.0 mg/dL<br>Urine:<br>Analytical Measuring Interval (AMI):<br>2.0–24.0 mg/dL<br>Extended Measuring Interval (EMI):<br>24.0-96.0 mg/dL | Serum/Plasma/Urine:<br>2.0-24.0 mg/dL |
| | Reportable Interval:<br>0.2–96.0 mg/dL | |
| Lower Limits of<br>Measurement | Serum/Plasma:<br>Limit of Blank (LoB): 0.1 mg/dL<br>Limit of Detection (LoD): 0.2 mg/dL<br>Limit of Quantitation (LoQ): 0.4 mg/dL<br>Urine:<br>LoB: 0.1 mg/dL<br>LoD: 0.2 mg/dL<br>LoQ: 0.5 mg/dL | Serum/Urine:<br>LoD: 0.5 mg/dL<br>LoQ: 1.0 mg/dL |

{8}------------------------------------------------

# Table VI.2
Assay Differences

{9}------------------------------------------------

## VII. Summary of Nonclinical Performance

All performance characteristics were obtained using the ARCHITECT c8000 System.

### A. Reportable Interval - Serum/Plasma

Based on the limit of quantitation (LoQ) and the limit of detection (LoD), precision, and linearity, the ranges over which results can be reported are provided below.

| | mg/dL |
|--------------------------------------|------------|
| Analytical Measuring Interval (AMI)a | 2.0 – 24.0 |
| Reportable Intervalb | 0.2 – 24.0 |

a AMI: The AMI 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.

{10}------------------------------------------------

## B. Reportable Interval – Urine

Based on the limit of quantitation (LoQ) and the limit of detection (LoD), precision, and linearity, the ranges over which results can be reported are provided below.

| | mg/dL |
|--------------------------------------|-------------|
| Analytical Measuring Interval (AMI)a | 2.0 – 24.0 |
| Extended Measuring Interval (EMI)b | 24.0 – 96.0 |
| Reportable Intervalc | 0.2 – 96.0 |

ª AMI: The AMI 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 upper limit of quantitation (ULoQ) to the ULoQ × dilution factor.

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

{11}------------------------------------------------

## C. Within-Laboratory Precision - Serum

#### 1. Within-Laboratory Precision (20-Day)

A study was performed based on guidance from CLSI EP05-A3. * Testing was conducted using 3 lots of the Calcium2 reagent, 3 lots of the Consolidated Chemistry Calibrator (ConCC), and 1 lot of commercially available controls and 3 instruments. Two controls and 3 human serum panels were tested in 2 replicates, 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.

| Sample | n | Mean<br>(mg/dL) | Within-Run<br>(Repeatability) | | Within-Laboratorya | |
|-----------------|----|-----------------|-------------------------------|-----|-----------------------|--------------------|
| | | | SD | %CV | SD<br>(Rangeb) | %CV<br>(Rangeb) |
| Control Level 1 | 80 | 9.5 | 0.07 | 0.8 | 0.07<br>(0.07 – 0.08) | 0.8<br>(0.8 – 0.9) |
| Control Level 2 | 80 | 12.7 | 0.08 | 0.7 | 0.09<br>(0.08 – 0.11) | 0.7<br>(0.6 – 0.9) |
| Panel A | 80 | 3.3 | 0.05 | 1.5 | 0.05<br>(0.05 – 0.07) | 1.5<br>(1.5 – 2.3) |
| Panel B | 80 | 6.3 | 0.05 | 0.8 | 0.07<br>(0.05 – 0.08) | 1.1<br>(0.8 – 1.3) |
| Panel C | 80 | 22.5 | 0.14 | 0.6 | 0.20<br>(0.19 – 0.20) | 0.9<br>(0.9 – 0.9) |

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

b Minimum and maximum SD or %CV across the 3 reagent lot/calibrator lot/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.

{12}------------------------------------------------

## 2. System Reproducibility

A study was performed based on guidance from the CLSI document EP05-A3. * Testing was conducted using 1 lot of the Calcium2 reagent, 1 lot of the ConCC, 1 lot of commercially available controls, and 3 instruments. Each instrument was operated by a different technician, and each technician prepared an individual sample set. Two controls and 3 human serum panels were tested in 3 replicates at 2 separate times per day on 5 different days.

| Sample | n | Mean<br>(mg/dL) | Repeatability | | Within-<br>Laboratorya | | Reproducibilityb | |
|--------------------|----|-----------------|---------------|-----|------------------------|-----|------------------|-----|
| | | | SD | %CV | SD | %CV | SD | %CV |
| Control<br>Level 1 | 90 | 9.4 | 0.09 | 0.9 | 0.10 | 1.1 | 0.13 | 1.4 |
| Control<br>Level 2 | 90 | 12.5 | 0.10 | 0.8 | 0.10 | 0.8 | 0.12 | 1.0 |
| Panel A | 90 | 3.3 | 0.05 | 1.5 | 0.05 | 1.5 | 0.08 | 2.6 |
| Panel B | 90 | 6.3 | 0.08 | 1.2 | 0.08 | 1.2 | 0.11 | 1.7 |
| Panel C | 90 | 22.2 | 0.18 | 0.8 | 0.19 | 0.9 | 0.19 | 0.9 |

ª Includes repeatability (within-run), between-run, and between-day variability.

b Includes repeatability (within-run), between-day, and between-instrument variability.

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

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

## D. Within-Laboratory Precision - Urine

#### 1. Within-Laboratory Precision (20-Day)

A study was performed based on guidance from CLSI EP05-A3. * Testing was conducted using 3 lots of the Calcium2 reagent, 3 lots of the ConCC, and 1 lot of commercially available controls and 3 instruments. Two controls and 3 human urine panels were tested in 2 replicates, 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 | |
|--------------------|----|-----------------|-------------------------------|-----|-----------------------|--------------------|--|
| | | Mean<br>(mg/dL) | SD | %CV | SD<br>(Rangeb) | %CV<br>(Rangeb) | |
| Sample | n | | | | | | |
| Control<br>Level 1 | 80 | 6.7 | 0.07 | 1.0 | 0.08<br>(0.05 - 0.08) | 1.1<br>(0.8 - 1.2) | |
| Control<br>Level 2 | 80 | 9.6 | 0.08 | 0.9 | 0.10<br>(0.06 - 0.10) | 1.0<br>(0.7 - 1.0) | |
| Panel A | 80 | 3.2 | 0.06 | 1.9 | 0.08<br>(0.04 - 0.08) | 2.5<br>(1.4 - 2.5) | |
| Panel B | 80 | 14.2 | 0.12 | 0.8 | 0.12<br>(0.10 - 0.12) | 0.9<br>(0.7 - 0.9) | |
| Panel C | 80 | 23.1 | 0.14 | 0.6 | 0.17<br>(0.14 - 0.17) | 0.7<br>(0.6 - 0.8) | |

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

b Minimum and maximum SD or %CV across the 3 reagent lot/calibrator lot/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.

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

#### 2. System Reproducibility

A study was performed based on guidance from the CLSI document EP05-A3. * Testing was conducted using 1 lot of the Calcium2 reagent, 1 lot of the ConCC, 1 lot of commercially available controls, and 3 instruments. Each instrument was operated by a different technician, and each technician prepared an individual sample set. Two controls and 3 human urine panels were tested in 3 replicates at 2 separate times per day on 5 different days.

| | | Mean | Repeatability | | Within-<br>Laboratoryª | | Reproducibilityb | |
|--------------------|----|---------|---------------|-----|------------------------|-----|------------------|-----|
| Sample | n | (mg/dL) | SD | %CV | SD | %CV | SD | %CV |
| Control<br>Level 1 | 90 | 6.9 | 0.06 | 0.9 | 0.07 | 1.0 | 0.10 | 1.4 |
| Control<br>Level 2 | 90 | 9.9 | 0.09 | 0.9 | 0.09 | 0.9 | 0.11 | 1.1 |
| Panel A | 90 | 3.1 | 0.06 | 1.8 | 0.07 | 2.2 | 0.09 | 2.9 |
| Panel B | 90 | 14.2 | 0.11 | 0.8 | 0.12 | 0.8 | 0.15 | 1.1 |
| Panel C | 90 | 23.1 | 0.18 | 0.8 | 0.18 | 0.8 | 0.23 | 1.0 |

a Includes repeatability (within-run), between-run, and between-day variability.

b Includes repeatability (within-run), between-day, and between-instrument variability.

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

{15}------------------------------------------------

## E. Accuracy

A study was performed to estimate the bias of the Calcium2 assay relative to standard reference material (NIST SRM 956d Level 1 and Level 2). Testing was conducted using 2 concentrations of the standard across 3 lots of the Calcium2 reagent, 2 lots of the Consolidated Chemistry Calibrator, and 1 instrument. The bias ranged from -3.7% to -0.6%.

#### F. Lower Limits of Measurement - Serum

A study was performed based on guidance from CLSI EP17-A2. * Testing was conducted using 3 lots of the Calcium2 reagent on each of 2 instruments over 3 days. The maximum observed limit of blank (LoB), limit of detection (LoD), and limit of quantitation (LoQ) values are summarized below.

| | mg/dL |
|------|-------|
| LoBa | 0.1 |
| LoDb | 0.2 |
| LoQc | 0.4 |

a The LoB represents 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 (CLSI). Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline-Second Edition. CLSI Document EP17-A2. Wayne, PA: CLSI; 2012.

{16}------------------------------------------------

#### G. Lower Limits of Measurement - Urine

A study was performed based on guidance from CLSI EP17-A2. * Testing was conducted using 3 lots of the Calcium2 reagent on each of 2 instruments over 3 days. The maximum observed limit of blank (LoB), limit of detection (LoD), and limit of quantitation (LoQ) values are summarized below.

| | mg/dL |
|------|-------|
| LoBa | 0.1 |
| LoDb | 0.2 |
| LoQc | 0.5 |

a The LoB represents 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.

#### H. Linearity - Serum

A study was performed based on guidance from CLSI EP06 2nd ed. *

The assay was demonstrated to be linear from 2.0 to 24.0 mg/dL.

## I. Linearity - Urine

A study was performed based on guidance from CLSI EP06 2nd ed.

The assay was demonstrated to be linear from 2.0 to 24.0 mg/dL

^* Clinical and Laboratory Standards Institute (CLSI). Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline-Second Edition. CLSI Document EP17-A2. Wayne, PA: CLSI: 2012.

^* Clinical and Laboratory Standards Institute (CLSI). Evaluation of the Linearity of Quantitative Measurement Procedure. 2nd ed. CLSI Document EP06. Wayne, PA: CLSI; 2020.

{17}------------------------------------------------

### J. Potentially Interfering Endogenous and Exogenous Substances - Serum

#### Potentially Interfering Endogenous Substances

A study was performed based on guidance from EP07 3rd ed. * Each substance was tested at 2 levels of the analyte (approximately 9 mg/dL and 12 mg/dL). No significant interference (interference within ± 5%) was observed at the following

concentrations.

| No Significant Interference (Interference within ± 5%) | |
|--------------------------------------------------------|-------------------|
| Potentially Interfering Substance | Interferent Level |
| Bilirubin (conjugated) | 40 mg/dL |
| Bilirubin (unconjugated) | 40 mg/dL |
| Hemoglobin | 1,000 mg/dL |
| Total protein | 15 g/dL |
| Triglycerides | 1500 mg/dL |

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

{18}------------------------------------------------

## Potentially Interfering Exogenous Substances

No significant interference (interference within ± 5%) was observed at the following concentrations.

| No Significant Interference (Interference within ± 5%) | |
|--------------------------------------------------------|-------------------|
| Potentially Interfering Substance | Interferent Level |
| Acetaminophen | 160 mg/L |
| Acetylcysteine | 150 mg/L |
| Acetylsalicylic acid | 30 mg/L |
| Ampicillin-Na | 80 mg/L |
| Ascorbic acid | 60 mg/L |
| Ca-dobesilate | 46 mg/L |
| Cefoxitin | 6600 mg/L |
| Cyclosporine | 2 mg/L |
| Doxycycline | 20 mg/L |
| Ibuprofen | 220 mg/L |
| Levodopa | 8 mg/L |
| Magnesium sulfate | 50 mg/dL |
| Methyldopa | 25 mg/L |
| Metronidazole | 130 mg/L |
| Phenylbutazone | 330 mg/L |
| Rifampicin | 50 mg/L |
| Sodium heparin | 4 U/mL |
| Theophylline (1,3-dimethylxanthine) | 60 mg/L |

{19}------------------------------------------------

Interference beyond ± 5% (based on 95% Confidence Intervals [CI]) was observed

at the concentrations shown below for the following substance

| Interference beyond ± 5% (based on 95% Confidence Interval [CI]) | | | |
|------------------------------------------------------------------|-------------------|---------------|----------------------------|
| Potentially Interfering<br>Substance | Interferent Level | Analyte Level | % Interference<br>(95% CI) |
| Ca-dobesilate | 60 mg/L | 9 mg/dL | 6%<br>(5%, 6%) |

{20}------------------------------------------------

## K. Potentially Interfering Endogenous and Exogenous Substances - Urine

#### Potentially Interfering Endogenous Substances

A study was performed based on guidance from EP07 3rd ed. * Each substance was tested at 2 levels of the analyte (approximately 8 mg/dL and 16 mg/dL). No significant interference (interference within ± 5%) was observed at the following concentrations.

| No Significant Interference (Interference within ± 5%) | |
|--------------------------------------------------------|-------------------|
| Potentially Interfering Substance | Interferent Level |
| Ascorbate | 100 mg/dL |
| Glucose | 500 mg/dL |
| Magnesium sulfate | 50 mg/dL |
| Total protein | 30 mg/dL |
| Sample pH | 2.5 to 6.0 |
| Urea | 5000 mg/dL |
| Uric acid | 92 mg/dL |

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

{21}------------------------------------------------

## Potentially Interfering Exogenous Substances

No significant interference (interference within±5%) was observed at the following concentrations.

| No Significant Interference (Interference within ± 5%) | | | |
|--------------------------------------------------------|-------------------|--|--|
| Potentially Interfering Substance | Interferent Level | | |
| Acetaminophen | 16 mg/dL | | |
| Acetic acid (8.5N) | 5.16 mL/dL | | |
| Boric acid | 250 mg/dL | | |
| Hydrochloric acid (6N) | 2.5 mL/dL | | |
| Ibuprofen | 22 mg/dL | | |
| Nitric acid (6N) | 5.0 mL/dL | | |

### Interference beyond ± 5% (based on 95% Confidence Intervals [CI]) was observed

at the concentrations shown below for the following substance

| Interference beyond ± 5% (based on 95% Confidence Interval [CI]) | | | |
|------------------------------------------------------------------|-------------------|---------------|----------------------------|
| Potentially Interfering<br>Substance | Interferent Level | Analyte Level | % Interference<br>(95% CI) |
| Acetic acid (8.5N) | 6.25 mL/dL | 8 mg/dL | -7%<br>(-8%, -6%) |

{22}------------------------------------------------

## L. Method Comparison - Serum

A study was performed based on guidance from CLSI EP09c 3rd ed. * using the Passing-Bablok regression method. The study compared the Calcium2 assay to the comparator Calcium assay.

| Calcium2 vs Calcium on the ARCHITECT c8000 System | | | | | | |
|---------------------------------------------------|-----|-------|-------------------------|-----------|-------|---------------------|
| | n | Units | Correlation Coefficient | Intercept | Slope | Concentration Range |
| Serum | 120 | mg/dL | 1.00 | -0.1 | 1.02 | 2.3–21.1 |

#### M. Method Comparison - Urine

A study was performed based on guidance from CLSI EP09c 3rd ed. * using the Passing-Bablok regression method. The study compared the Calcium2 assay to the comparator Calcium assay.

| Calcium2 vs Calcium on the ARCHITECT c8000 System | | | | | | |
|---------------------------------------------------|-----|-------|-------------------------|-----------|-------|---------------------|
| | n | Units | Correlation Coefficient | Intercept | Slope | Concentration Range |
| Urine | 112 | mg/dL | 1.00 | 0.1 | 0.96 | 2.1–22.7 |

^* Clinical and Laboratory Standards Institute (CLSI). Measurement Procedure Comparison and Bias Estimation Using Patient Samples.3rd ed. CLSI Document EP09c. Wayne, PA: CLSI; 2018.

^* Clinical and Laboratory Standards Institute (CLSI). Measurement Procedure Comparison and Bias Estimation Using Patient Samples.3rd ed. CLSI Document EP09c. Wayne, PA: CLSI; 2018.

{23}------------------------------------------------

## N. Tube Type Equivalence - Serum

A study was performed to evaluate the suitability of specific blood collection tube types for use with the Calcium2 assay. Samples were collected from 78 donors and evaluated across tube types. The following blood collection tube types were determined to be acceptable for use with the Calcium2 assay:

## Serum

- Serum tubes •
- Serum separator tubes •

## Plasma

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

{24}------------------------------------------------

#### O. Dilution Verification - Urine

A study was performed based on guidance from CLSI EP34 1st ed. * to evaluate the recovery of the Calcium2 automated and manual dilution, relative to the assigned concentration, on the ARCHITECT c System.

Five samples were prepared to have calcium concentrations within the EMI of the Calcium2 assay by spiking normal human urine with calcium stock (calcium chloride dihydrate solution) to the target concentration values of 26, 41, 56, 71, and 85 mg/dL.

The performance of the automated dilution protocol and manual dilution procedure was considered acceptable if, for samples within the EMI, the dilution recovery was within or equal to 100% ± 10% when comparing auto-diluted or manually diluted samples to target or assigned concentrations and the imprecision was ≤ 5 %CV for the automated dilution protocol and < 6 %CV for manual dilution procedure.

The %recovery for the automated dilution and the manual dilution demonstrated acceptable performance.

The dilution reproducibility demonstrated imprecision ≤ 5 %CV for the automated dilution protocol and ≤ 6 %CV for manual dilution procedure.

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

{25}------------------------------------------------

## VIII. Summary of Clinical Performance

This section does not apply.

## IX. Conclusion Drawn from Nonclinical Laboratory Studies

The results presented in this 510(k) premarket notification demonstrate that the performance of the subject device Calcium2 (LN 04S91), is substantially equivalent to the predicate device, ARCHITECT Calcium (k062855).

The similarities and differences between the subject device and the predicate device are presented in Section VI.