(42 days)
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).
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
The provided text describes the performance validation of the Calcium2 assay, specifically for its use in quantitating calcium in human serum, plasma, or urine on the ARCHITECT c System. This is a Class II medical device (Calcium test system), regulated under 21 CFR 862.1145, product code CJY.
Here's an analysis based on the request:
Device: Calcium2 assay
Intended Use: Quantitation of calcium in human serum, plasma, or urine on the ARCHITECT c System. Used in the diagnosis and treatment of parathyroid disease, various bone diseases, chronic renal disease, and tetany.
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly outline a pre-defined table of "acceptance criteria" against which each test result is measured, as would be common for AI/ML performance studies. Instead, it presents various performance characteristics with their measured values, often referencing CLSI guidelines for the methodology. The "acceptance" can be inferred from the reported values and the conclusion of substantial equivalence. For quantitative assays like this, performance is typically assessed against established industry standards for precision, accuracy, linearity, and interference.
However, we can infer some "acceptance criteria" implicitly from the context of "acceptable performance" and the ranges presented.
| Performance Characteristic | Acceptance Criteria (Implicit/Standard) | Reported Device Performance |
|---|---|---|
| Reportable Interval (Serum/Plasma) | ||
| Analytical Measuring Interval (AMI) | Defined as the range demonstrating acceptable linearity, imprecision, and bias. | 2.0 – 24.0 mg/dL |
| Reportable Interval | Extends from LoD to upper AMI. | 0.2 – 24.0 mg/dL |
| Reportable Interval (Urine) | ||
| Analytical Measuring Interval (AMI) | Defined as the range demonstrating acceptable linearity, imprecision, and bias. | 2.0 – 24.0 mg/dL |
| Extended Measuring Interval (EMI) | Requires acceptable dilution performance (recovery, imprecision). | 24.0 – 96.0 mg/dL (Dilution recovery within 100% ± 10%, imprecision ≤ 5 %CV for automated dilution, ≤ 6 %CV for manual dilution) |
| Reportable Interval | Extends from LoD to upper EMI. | 0.2 – 96.0 mg/dL |
| Precision (Within-Laboratory - Serum, 20-Day) | ||
| %CV (Control Level 1) | Implied to be acceptable based on CLSI EP05-A3 guidance. | Within-Run: 0.8%; Within-Laboratory: 0.8% (Range 0.8-0.9%) |
| %CV (Control Level 2) | Implied to be acceptable based on CLSI EP05-A3 guidance. | Within-Run: 0.7%; Within-Laboratory: 0.7% (Range 0.6-0.9%) |
| %CV (Panel C, highest conc.) | Implied to be acceptable based on CLSI EP05-A3 guidance. | Within-Run: 0.6%; Within-Laboratory: 0.9% (Range 0.9-0.9%) |
| Precision (System Reproducibility - Serum) | ||
| %CV (Control Level 1) | Implied to be acceptable based on CLSI EP05-A3 guidance. | Repeatability: 0.9%; Within-Laboratory: 1.1%; Reproducibility: 1.4% |
| %CV (Panel A, lowest conc.) | Implied to be acceptable based on CLSI EP05-A3 guidance. | Repeatability: 1.5%; Within-Laboratory: 1.5%; Reproducibility: 2.6% |
| Accuracy (Bias) | ||
| Bias against NIST SRM 956d | Implied to be acceptable. | Ranged from -3.7% to -0.6% |
| Lower Limits of Measurement (Serum) | ||
| LoB | 95th percentile from zero-analyte samples. | 0.1 mg/dL |
| LoD | Lowest concentration detected with 95% probability. | 0.2 mg/dL |
| LoQ | Lowest concentration at which max 20%CV met. | 0.4 mg/dL |
| Interference (Serum, Endogenous & Exogenous) | ||
| No significant interference | Interference within ± 5%. | Most substances showed no significant interference (e.g., Bilirubin up to 40 mg/dL, Hemoglobin up to 1000 mg/dL, Acetaminophen up to 160 mg/L). One exception: Ca-dobesilate at 60 mg/L showed 6% interference (95% CI: 5%, 6%). |
| Method Comparison (Serum & Urine) | ||
| Correlation Coefficient | Implied to be close to 1.00 for equivalence. | Serum: 1.00; Urine: 1.00 |
| Slope | Implied to be close to 1.00 for equivalence. | Serum: 1.02; Urine: 0.96 |
| Intercept | Implied to be close to 0.00 for equivalence. | Serum: -0.1; Urine: 0.1 |
| Dilution Verification (Urine) | ||
| %Recovery | Within 100% ± 10%. | Acceptable performance demonstrated. |
| Imprecision (Automated Dilution) | ≤ 5 %CV. | ≤ 5 %CV. |
| Imprecision (Manual Dilution) | ≤ 6 %CV. | ≤ 6 %CV. |
2. Sample Size Used for the Test Set and the Data Provenance
The provided information is for an in-vitro diagnostic (IVD) test, not an AI/ML model for image analysis. Therefore, the "test set" and "training set" terminology from an AI/ML perspective doesn't directly apply in the same way. Instead, the studies involved various types of samples (controls, panels, human serum/plasma/urine samples) tested under specific experimental designs.
- Precision Studies (Serum & Urine, 20-Day):
- Sample Size: 80 replicates per sample type (2 controls, 3 human panels) for each of the 3 reagent lot/calibrator lot/instrument combinations in the 20-day study. (e.g., 5 samples * 80 replicates = 400 total data points per combination shown in the table).
- Data Provenance: Not explicitly stated (e.g., country of origin). The studies are "within-laboratory" meaning they were conducted in a controlled lab setting, likely at the manufacturer's site or a designated testing facility. The nature of these samples (human serum/urine panels) suggests they are likely representative, but the specific collection method or origin (retrospective/prospective collection from patients) is not detailed.
- System Reproducibility Studies (Serum & Urine):
- Sample Size: 90 replicates per sample type (2 controls, 3 human panels).
- Data Provenance: Same as above, not explicitly stated.
- Accuracy Study:
- Sample Size: Not explicitly stated for replicates, but involved 2 concentrations of NIST SRM 956d standard.
- Data Provenance: NIST standard reference material, a highly controlled and traceable source.
- Lower Limits of Measurement Studies (Serum & Urine):
- Sample Size: n ≥ 60 replicates for zero-analyte and low-analyte level samples for LoB, LoD, and LoQ determination.
- Data Provenance: Not explicitly stated.
- Linearity Studies (Serum & Urine):
- Sample Size: Not explicitly stated how many points were measured across the range, but demonstrated linearity from 2.0 to 24.0 mg/dL.
- Data Provenance: Not explicitly stated.
- Interference Studies (Serum & Urine):
- Sample Size: Not explicitly stated how many replicates, but each substance was tested at 2 levels of the analyte.
- Data Provenance: Not explicitly stated.
- Method Comparison Studies (Serum & Urine):
- Sample Size: 120 serum samples, 112 urine samples.
- Data Provenance: Patient samples. Not explicitly stated if retrospective or prospective collection.
- Tube Type Equivalence Study (Serum):
- Sample Size: Samples from 78 donors.
- Data Provenance: Donor samples. Not explicitly stated if retrospective or prospective.
- Dilution Verification (Urine):
- Sample Size: 5 samples prepared with calcium stock. Replicates for dilution recovery and imprecision were performed but the exact number isn't specified beyond "demonstrated acceptable performance."
- Data Provenance: Prepared samples.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts
This type of IVD device (quantitative chemical assay) relies on objective measurement against a known reference (e.g., NIST standard) or internal validated methods, rather than subjective expert consensus. Therefore, "ground truth" is established through highly controlled laboratory procedures and certified reference materials, not typically through multiple human experts adjudicating results. The "experts" involved are likely laboratory scientists and metrologists operating under strict quality systems (CLSI guidelines, ISO standards).
4. Adjudication Method (e.g. 2+1, 3+1, none) for the Test Set
Not applicable for a quantitative chemical assay. Results are objectively measured by the instrument and verified through calibration and quality control. There is no subjective interpretation requiring adjudication.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
Not applicable. This is an in-vitro diagnostic test, not an AI/ML-driven imaging or diagnostic tool that assists human readers.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
This is a standalone quantitative assay. The Calcium2 device automatically measures calcium concentration. Human involvement is in sample preparation, loading, and interpreting the numerical output. Its performance is evaluated entirely as an automated system.
7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)
The ground truth for this device's performance validation is established primarily through:
- Reference Materials: For accuracy (e.g., NIST SRM 956d for bias estimation).
- Known Concentrations: For linearity, lower limits of measurement, and dilution verification, samples are prepared with known concentrations of calcium or spiked with calcium.
- Comparative Methods: For method comparisons, the "ground truth" is implicitly the performance of the legally marketed predicate device (Abbott Clinical Chemistry Architect/Aeroset Calcium, K062855), which serves as the comparator.
- Statistical Models/Guidelines: CLSI guidelines (EP05-A3, EP09c, EP17-A2, EP06, EP07, EP34) provide the statistical framework and methodology for validating performance characteristics like precision, linearity, and interference.
8. The Sample Size for the Training Set
Not applicable in the typical AI/ML sense. This is a chemistry assay, not a machine learning model that undergoes a "training" phase with a large dataset. The "training" for such a device involves rigorous engineering, chemical formulation, and calibration development, rather than data-driven model training.
9. How the Ground Truth for the Training Set Was Established
As above, "training set" is not a concept for this type of device. The accuracy and reliability of the assay are built into its chemical design, reagent formulation, and instrument calibration process. These processes rely on highly accurate reference standards (like NIST) and established analytical chemistry principles to ensure the device measures calcium correctly across its analytical range.
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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"
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(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.
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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 (DICE@fda.hhs.gov) or phone (1-800-638-2041 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
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Indications for Use
Submission Number (if known)
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)
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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: (224) 668-1435 Fax: (224) 667-4836 Email: cherie.lipowsky(@abbott.com
Secondary contact person for all communications:
Jacob Richards, Associate Director of Regulatory Affairs Abbott Diagnostics Division Phone: (224) 668-8852 Fax: (224) 667-4836 Email: jacob.richards(@abbott.com
Date Summary Prepared: February 07, 2025
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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.
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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.
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Table VI.1
Assay Similarities
| Characteristics | Subject DeviceCalcium2 (List Number [LN] 04S91)(K244042) | Predicate DeviceAbbott Clinical Chemistry Architect/AerosetCalcium (LN 3L79)(K062855) |
|---|---|---|
| Intended Use andIndications for Use | The Calcium2 assay is used for the quantitation ofcalcium in human serum, plasma, or urine on theARCHITECT c System.Calcium measurements are used in the diagnosis andtreatment of parathyroid disease, a variety of bonediseases, chronic renal disease and tetany (intermittentmuscular contractions or spasms). | The Calcium assay is used for the quantitation of calcium inhuman serum, plasma, or urine.Calcium measurements are used in the diagnosis andtreatment of parathyroid disease, a variety of bone diseases,chronic renal disease and tetany (intermittent muscularcontractions or spasms). |
| Methodology | Arsenazo III | Same |
| Specimen Type | Human serum, plasma, or urine | Same |
| Assay Principle/Principle ofProcedure | The Calcium2 assay is an automated clinical chemistryassay. Arsenazo III dye reacts with calcium in an acidsolution to form a blue-purple complex. The colordeveloped is measured at 660 nm and is proportional tothe calcium concentration in the sample. | Same |
| Use of Calibrators | Yes | Same |
| Use of Controls | Yes | Same |
| Traceability | NIST SRM 956 | Same |
| Characteristics | Subject DeviceCalcium2 (List Number [LN] 04S91)(K244042) | Predicate DeviceAbbott Clinical Chemistry Architect/AerosetCalcium (LN 3L79)(K062855) |
| Platform | ARCHITECT c8000 System | AEROSET and ARCHITECT c8000 System |
| Assay Range | Serum/Plasma:Analytical Measuring Interval (AMI):2.0–24.0 mg/dLReportable Interval:0.2–24.0 mg/dLUrine:Analytical Measuring Interval (AMI):2.0–24.0 mg/dLExtended Measuring Interval (EMI):24.0-96.0 mg/dL | Serum/Plasma/Urine:2.0-24.0 mg/dL |
| Reportable Interval:0.2–96.0 mg/dL | ||
| Lower Limits ofMeasurement | Serum/Plasma:Limit of Blank (LoB): 0.1 mg/dLLimit of Detection (LoD): 0.2 mg/dLLimit of Quantitation (LoQ): 0.4 mg/dLUrine:LoB: 0.1 mg/dLLoD: 0.2 mg/dLLoQ: 0.5 mg/dL | Serum/Urine:LoD: 0.5 mg/dLLoQ: 1.0 mg/dL |
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Table VI.2
Assay Differences
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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.
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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.
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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(mg/dL) | Within-Run(Repeatability) | Within-Laboratorya | ||
|---|---|---|---|---|---|---|
| SD | %CV | SD(Rangeb) | %CV(Rangeb) | |||
| Control Level 1 | 80 | 9.5 | 0.07 | 0.8 | 0.07(0.07 – 0.08) | 0.8(0.8 – 0.9) |
| Control Level 2 | 80 | 12.7 | 0.08 | 0.7 | 0.09(0.08 – 0.11) | 0.7(0.6 – 0.9) |
| Panel A | 80 | 3.3 | 0.05 | 1.5 | 0.05(0.05 – 0.07) | 1.5(1.5 – 2.3) |
| Panel B | 80 | 6.3 | 0.05 | 0.8 | 0.07(0.05 – 0.08) | 1.1(0.8 – 1.3) |
| Panel C | 80 | 22.5 | 0.14 | 0.6 | 0.20(0.19 – 0.20) | 0.9(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.
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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(mg/dL) | Repeatability | Within-Laboratorya | Reproducibilityb | |||
|---|---|---|---|---|---|---|---|---|
| SD | %CV | SD | %CV | SD | %CV | |||
| ControlLevel 1 | 90 | 9.4 | 0.09 | 0.9 | 0.10 | 1.1 | 0.13 | 1.4 |
| ControlLevel 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.
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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(Repeatability) | Within-Laboratorya | ||||||
|---|---|---|---|---|---|---|---|
| Mean(mg/dL) | SD | %CV | SD(Rangeb) | %CV(Rangeb) | |||
| Sample | n | ||||||
| ControlLevel 1 | 80 | 6.7 | 0.07 | 1.0 | 0.08(0.05 - 0.08) | 1.1(0.8 - 1.2) | |
| ControlLevel 2 | 80 | 9.6 | 0.08 | 0.9 | 0.10(0.06 - 0.10) | 1.0(0.7 - 1.0) | |
| Panel A | 80 | 3.2 | 0.06 | 1.9 | 0.08(0.04 - 0.08) | 2.5(1.4 - 2.5) | |
| Panel B | 80 | 14.2 | 0.12 | 0.8 | 0.12(0.10 - 0.12) | 0.9(0.7 - 0.9) | |
| Panel C | 80 | 23.1 | 0.14 | 0.6 | 0.17(0.14 - 0.17) | 0.7(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.
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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-Laboratoryª | Reproducibilityb | |||||
|---|---|---|---|---|---|---|---|---|
| Sample | n | (mg/dL) | SD | %CV | SD | %CV | SD | %CV |
| ControlLevel 1 | 90 | 6.9 | 0.06 | 0.9 | 0.07 | 1.0 | 0.10 | 1.4 |
| ControlLevel 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.
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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.
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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.
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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.
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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 |
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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 InterferingSubstance | Interferent Level | Analyte Level | % Interference(95% CI) |
| Ca-dobesilate | 60 mg/L | 9 mg/dL | 6%(5%, 6%) |
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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.
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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 InterferingSubstance | Interferent Level | Analyte Level | % Interference(95% CI) |
| Acetic acid (8.5N) | 6.25 mL/dL | 8 mg/dL | -7%(-8%, -6%) |
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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.
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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 •
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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.
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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.
§ 862.1145 Calcium test system.
(a)
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).(b)
Classification. Class II.