(86 days)
ELITech Clinical Systems CALCIUM ARSENAZO is intended for the quantitative in vitro diagnostic determination of total calcium in human serum, plasma and urine using ELITech Clinical Systems Selectra Pro Series Analyzers.
It is not intended for use in Point of Care settings.
Calcium measurements are used in the diagnosis and treatment of parathyroid diseases, chronic renal disease and tetany (intermittent muscular contractions or spasms).
ELITech Clinical Systems CALCIUM ARSENAZO is available as a kit only. It consists of a mono-reagent R whose composition is: 100 mmol/L MES buffer (pH 6.50), 200 µmol/L Arsenazo III.
This document describes the performance of the ELITech Clinical Systems CALCIUM ARSENAZO IVD device. The information provided outlines the analytical performance characteristics and comparison studies rather than clinical or AI-assisted studies typically associated with detailed acceptance criteria of AI/ML-based medical devices.
Therefore, many of the requested categories (e.g., number of experts, adjudication methods, MRMC studies, effect size of AI improvement, standalone AI performance) are not applicable to this type of device submission, which is for an in vitro diagnostic reagent. The "ground truth" here refers to established analytical methods and reference materials, not expert consensus on medical images or clinical outcomes data.
Here's a breakdown of the available information based on your request, focusing on the analytical performance studies conducted for this IVD reagent:
1. Table of Acceptance Criteria (Implicit) and Reported Device Performance:
The document doesn't present explicit "acceptance criteria" in a singular table for all performance characteristics against which the device passed or failed, but rather describes the methodology and results for each analytical performance study. The "acceptance criteria" are generally implied by standard clinical laboratory practices and regulatory expectations for IVD devices (e.g., CLSI guidelines, demonstrating substantial equivalence).
Device Performance Summaries (from the document):
| Performance Characteristic | Acceptance Criteria (Implicit/Standard Practice) | Reported Device Performance (ELITech Clinical Systems CALCIUM ARSENAZO) |
|---|---|---|
| Precision (Serum) | Based on CLSI EP05-A2 protocol (Guideline for acceptable CV%) | Level 1: Within-run CV% 1.1, Total CV% 1.7 (Mean 8.28 mg/dL) |
| Level 2: Within-run CV% 0.5, Total CV% 1.4 (Mean 10.32 mg/dL) | ||
| Level 3: Within-run CV% 0.5, Total CV% 1.0 (Mean 12.96 mg/dL) | ||
| Precision (Urine) | Based on CLSI EP05-A2 protocol (Guideline for acceptable CV%) | Level 1: Within-run CV% 1.3, Total CV% 1.8 (Mean 4.53 mg/dL) |
| Level 2: Within-run CV% 0.5, Total CV% 1.2 (Mean 10.89 mg/dL) | ||
| Level 3: Within-run CV% 0.3, Total CV% 0.8 (Mean 17.51 mg/dL) | ||
| Linearity/Assay Range | Based on CLSI EP06-A protocol (Demonstrate linearity across intended range) | Serum: 5.00 - 15.00 mg/dL, with auto-dilution up to 90.00 mg/dL |
| Urine: 1.50 - 18.00 mg/dL | ||
| On-Board Stability | Deviations from D0 results within acceptance criteria for stability period | 28 days |
| Real-Time Stability | Stable until expiry date | 24 months at 2-8°C |
| Limit of Detection (LoD) | Based on CLSI EP17-A protocol | Serum: 0.04 mg/dL |
| Urine: 0.15 mg/dL | ||
| Limit of Quantification (LoQ) | Based on CLSI EP17-A protocol (e.g., Total Error ≤ 0.32 mg/dL for serum LoQ) | Serum: 5.00 mg/dL |
| Urine: 1.50 mg/dL | ||
| Interference (Serum) | Acceptance criteria: ±10% bias | No significant interference up to specified concentrations for various substances (see table in original text). Minor interference from some monoclonal gammopathies. |
| Interference (Urine) | Acceptance criteria: ±10% bias | No significant interference up to specified concentrations for various substances and pH range (see table in original text). |
| Method Comparison (Serum) | Based on CLSI EP09-A2 protocol (Good correlation with predicate device) | y = 0.949x + 0.41 mg/dL; r = 0.993; r² = 0.986; Sy.x = 0.29 mg/dL (vs. predicate device) |
| Method Comparison (Urine) | Based on CLSI EP09-A2 protocol (Good correlation with predicate device) | y = 0.936x + 0.20 mg/dL; r = 0.995; r² = 0.990; Sy.x = 0.39 mg/dL (vs. predicate device) |
| Matrix Effect (Serum/Plasma) | Based on CLSI EP09-A2 protocol (Good correlation between serum and plasma) | y = 0.976x + 0.26 mg/dL; r = 1.000; r² = 0.993; Sy.x = 0.19 mg/dL (serum vs. lithium heparin plasma) |
2. Sample Size and Data Provenance:
- Precision Studies: 80 measurements for each of 3 levels for both serum and urine (total of 160 measurements per sample type across 20 operating days on 2 instruments).
- Linearity Studies: 11 levels of mixed samples for both serum and urine.
- Interference Studies: For each interferent, 2 sample pools (low and high calcium concentration) were tested, with aliquots spiked at various concentrations (7-9 different concentrations). Each point was measured in triplicate per run.
- Method Comparison (Serum): 106 serum patient samples.
- Method Comparison (Urine): 52 urine patient samples.
- Matrix Effect: 63 paired serum and plasma patient specimens.
Data Provenance: The document generally refers to "patient samples" but does not specify the country of origin. The studies are described as analytical performance evaluations, typically performed retrospectively on collected samples in a controlled laboratory setting. The submitting company is based in France.
3. Number of Experts and Qualifications:
Not applicable for this type of IVD analytical performance study. The ground truth for this device is based on quantitative chemical measurements, established analytical methods (e.g., predicate device, reference methods), and certified reference materials (NIST SRM 956c). Expertise is in analytical chemistry and clinical laboratory science for study design and interpretation, not expert medical opinion on, for example, image interpretation.
4. Adjudication Method:
None applicable. This is an analytical device for quantitative determination, not a diagnostic aid requiring adjudication of clinical findings or interpretations.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
Not applicable. This is an IVD reagent, not an AI/ML-based diagnostic system for human-in-the-loop assistance.
6. Standalone (Algorithm Only) Performance:
This device is a chemical reagent. Its performance is inherent to its chemical reaction and measurement on a specific analyzer (ELITech Clinical Systems Selectra Pro Series Analyzers). Therefore, the concept of "standalone performance" as it applies to an AI algorithm is not applicable. The reported performance metrics (precision, linearity, LoD, LoQ, interference) are its standalone analytical performance.
7. Type of Ground Truth Used:
The ground truth for the analytical performance studies is established by:
- Reference materials: Such as NIST SRM 956c for traceability of calibration.
- Established analytical methods: Comparison against a legally marketed predicate device (ABX Pentra Calcium AS CP) and adherence to CLSI (Clinical and Laboratory Standards Institute) protocols (e.g., EP05-A2 for precision, EP06-A for linearity, EP17-A for detection limits, EP07-A2 for interference, EP09-A2 for method comparison).
- Gravimetric or Volumetric Preparations: For linearity and interference studies, samples are prepared by mixing known concentrations or spiking with known amounts of analytes/interferents.
8. Sample Size for Training Set:
Not applicable. This device is a chemical reagent, not an AI/ML model that requires a "training set." The performance characteristics are determined through standard analytical validation studies.
9. How the Ground Truth for the Training Set Was Established:
Not applicable for the same reason as above.
{0}------------------------------------------------
Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized caduceus symbol, which is a staff with two snakes entwined around it. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the caduceus symbol.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
July 22, 2015
ELITECH GROUP DEBRA HUTSON VP RA/QA 21720 23RD DRIVE SE, SUITE 150 BOTHELL WA 98021
Re: K151113
Trade/Device Name: ELITech Clinical Systems CALCIUM ARSENAZO Regulation Number: 21 CFR 862.1145 Regulation Name: Calcium test system Regulatory Class: II Product Code: CJY Dated: April 23, 2015 Received: April 27, 2015
Dear Debra Hutson:
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. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21. Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
{1}------------------------------------------------
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. 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
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours.
Courtney H. Lias -S
Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
{2}------------------------------------------------
Indications for Use
510(k) Number (if known) K151113
Device Name
ELITech Clinical Systems CALCIUM ARSENAZO
Indications for Use (Describe)
ELITech Clinical Systems CALCIUM ARSENAZO is intended for the quantitative in vitro diagnostic determination of total calcium in human serum, plasma and urine using ELITech Clinical Systems Selectra Pro Series Analyzers.
It is not intended for use in Point of Care settings.
Calcium measurements are used in the diagnosis and treatment of parathyroid 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."
{3}------------------------------------------------
510(k) Summary
ELITech Clinical Systems CALCIUM ARSENAZO
| 1. | Date: | April 23, 2015 |
|---|---|---|
| 2. | Submitter: | ELITech Clinical Systems SASZone Industrielle61500 SEESFRANCE |
| 3. | Contact Person: | Debra K. HutsonVP RA/QA, EGI21720 23rd Dr SE, Suite 150Bothell, WA 98021Phone: 425-482-5174Fax:425-482-5550Email: d.hutson@elitechgroup.com |
| 4. | Device Name:Classification: | ELITech Clinical Systems CALCIUM ARSENAZO IIIClass IICJYClinical Chemistry21 CFR 862.1145 |
| 5. | Predicate Device: | K123171HORIBA ABXABX PENTRA CALCIUM AS CP |
{4}------------------------------------------------
- Intended Use:
ELITech Clinical Systems CALCIUM ARSENAZO is intended for the quantitative in vitro diagnostic determination of total calcium in human serum, plasma and urine using ELITech Clinical Systems Selectra Pro Series Analyzers. It is not intended for use in Point of Care settings. 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).
Special conditions for use statement(s):
Rx only.
This device is intended for professional use and in vitro diagnostic use only. CAUTION: Federal Law restricts this device to sale by or on the order of a licensed healthcare practitioner.
Special instrument requirements:
For use with ELITech Clinical Systems Selectra Pro Series Analyzers. Performance data was obtained on the Selectra ProM Analyzer.
7. Device Descriptions
ELITech Clinical Systems CALCIUM ARSENAZO is available as a kit only. It consists of a mono-reagent R whose composition is: 100 mmol/L MES buffer (pH 6.50), 200 µmol/L Arsenazo III.
8. Substantial Equivalence Information Assay (reagent)
-
- Predicate Device Name
- ABX PENTRA CALCIUM AS CP
-
- Comparison with predicate
Similarities
| Parameter | New DeviceELITech Clinical SystemsCALCIUM ARSENAZO | Predicate DeviceABX PENTRA CALCIUM AS CP,K123171 |
|---|---|---|
| Intended Use | ELITech Clinical Systems CALCIUMARSENAZO is intended for thequantitative in vitro diagnosticdetermination of total calcium inhuman serum, plasma and urine usingELITech Clinical Systems Selectra ProSeries Analyzers.It is not intended for use in Point ofCare settings. | ABX Pentra Calcium AS CP reagent,with associated calibrator and controls,is a diagnostic reagent for quantitativein vitro determination of calcium inhuman serum, plasma and urine basedon a colourimetric method, using theABX Pentra 400 Clinical Chemistryanalyzer. |
{5}------------------------------------------------
| Parameter | New DeviceELITech Clinical SystemsCALCIUM ARSENAZO | Predicate DeviceABX PENTRA CALCIUM AS CP,K123171 |
|---|---|---|
| Indication forUse | Calcium measurements are used inthe diagnosis and treatment ofparathyroid disease, a variety of bonediseases, chronic renal disease andtetany (intermittent muscularcontractions or spasms). | Measurements of calcium is used in thediagnosis and treatment of parathyroiddisease, a variety of bone diseases,chronic renal disease and tetany(intermittent muscular contractions orspasms). |
| Sample Type | Serum, Plasma, Urine | Same |
| AssayTechnology | Colorimetric test | Same |
| Composition | Reagent R:MES Buffer, pH 6.50 100 mmol/LArsenazo III 200 μmol/L | Same |
| Appearanceof reagents | Liquid form, ready to use | Same |
Differences
| Parameter | New DeviceELITech Clinical SystemsCALCIUM ARSENAZO | Predicate DeviceABX PENTRA CALCIUM AS CP,K123171 |
|---|---|---|
| Assay Format | 12 x 20 mL | 1 x 79 mL |
| Storage &Expiry | Store at 2-8°C and protect from light.The reagent is stable until the expirydate stated on the label. | Reagents, in unopened cassettes, arestable up to the expiry date on the labelif stored at 2-8°C and contamination isavoided. |
| Assay Range | Serum, Plasma : 5.00 - 15.00 mg/dLUrine: 1.50 - 18.00 mg/dL | Serum, Plasma : 4.00 - 18.05 mg/dLUrine: 0.64 - 18.05 mg/dL |
| Instrument | Selectra Pro M | ABX Pentra 400 |
| ReferenceValues | Serum/ Plasma :8.6 - 10.3 mg/dL2.15 - 2.57 mmol/LUrine (for a urinary volume of 1.5 Lper day) :100 - 300 mg/24h2.50 - 7.50 mmol/24hCalcemia is always interpretedaccording to the plasmatic proteinrates. | Serum / Plasma : 8.6 - 10.3 mg/dL(2.15 - 2.57 mmol/L)Urine :Women: < 250 mg/24h (6.24 mmol/24h)Men: < 300 mg/24h (7.49 mmol/24h) |
| Parameter | New DeviceELITech Clinical SystemsCALCIUM ARSENAZO | Predicate DeviceABX PENTRA CALCIUM AS CP,K123171 |
| Controls | Recommended quality controlmaterial (not included):ELITech Clinical Systems ELITROL I(Normal control) (cleared in K110830)ELITech Clinical Systems ELITROL II(Pathologic control) (cleared inK110830) | Recommended quality control material(not included):ABX Pentra N ControlABX Pentra P ControlABX Pentra Urine Control |
| Calibrator | Recommended calibration material(not included):ELITech Clinical Systems ELICAL 2(cleared in K110830) | Recommended calibration material (notincluded):ABX Pentra MultiCal |
| Limit ofDetection | Serum/Plasma: 0.04 mg/dLUrine: 0.15 mg/dL | Serum/Plasma: 0.28 mg/dLUrine: 0.23 mg/dL |
| Limit ofQuantitation | Serum/Plasma: 5.00 mg/dL | Serum/Plasma: 1.54 mg/dL |
| Urine: 1.50 mg/dL | Urine: 0.64 mg/dL | |
| Interferences-Serum/Plasma | Unconjugated bilirubin: Nosignificant interference up to30.0 mg/dL (513 µmol/L).Conjugated bilirubin: No significantinterference up to 29.5 mg/dL (504µmol/L).Hemoglobin: No significantinterference up to 500 mg/dL.Triglycerides: No significantinterference up to 1726 mg/dL.Magnesium: No significantinterference up to 12.0 mg/dLAscorbic acid: No significantinterference up to 20.0 mg/dL.Acetylsalicylic Acid: No significantinterference up to 200 mg/dL.Acetaminophen: No significantinterference up to 30 mg/dL. | Total Bilirubin: No significant influenceis observed up to 788 µmol/L(46.1 mg/dL).Direct Bilirubin: No significantinfluence is observed up to 445 µmol/L(26.0 mg/dL).Haemoglobin: No significant influenceis observed up to 290 µmol/L (500mg/dL).Lipemia: No significant influence isobserved up to an Intralipid®concentration (representative oflipemia) of 500 mg/dL.Magnesium: No significant influence isobserved up to 4.42 mmol/L (10.7mg/dL).Ascorbic Acid: No significant influenceis observed up to 3.40 mmol/L (60mg/dL).Acetylsalicylic Acid: No significantinfluence is observed up to 3.62 mmol/L(65.2 mg/dL).Acetaminophen: No significantinfluence is observed up to 1324 µmol/L(20 mg/dL).Ibuprofen: No significant influence isobserved up to 2.42 mmol/L (50.1mg/dL). |
| Parameter | New DeviceELITech Clinical SystemsCALCIUM ARSENAZO | Predicate DeviceABX PENTRA CALCIUM AS CP,K123171 |
| Interferences -Urine | Conjugated bilirubin: No significantinterference up to 29.5 mg/dL (504μmol/L).Hemoglobin: No significantinterference up to 500 mg/dLAscorbic acid: No significantinterference up to 20.0 mg/dL.Urea: No significant interference upto 5000 mg/dL.Uric Acid: No significant interferenceup to 100 mg/dL.Magnesium: No significantinterference up to 10.0 mg/dLpH: No significant interference for pHvalues ranging between 2.5 and 6.0. | Direct Bilirubin: No significantinfluence is observed up to 432 μmol/L(25.3 mg/dL).Haemoglobin: No significant influenceis observed up to 290 μmol/L (500mg/dL).Ascorbic Acid: No significant influenceis observed up to 3.40 mmol/L (60mg/dL).Lipemia: No significant influence isobserved up to an Intralipid®concentration (representative oflipemia) of 200 mg/dL.Magnesium: No significant influence isobserved up to 5.34 mmol/L (13.0mg/dL).pH: The urine should not be alkalinized. |
| On-boardstability | 28 days | 60 days |
| Calibrationfrequency | Calibration frequency: 28 daysRecalibrate when reagent lotschange, when quality control resultsfall outside the established range,and after a maintenance operation. | The reagent is calibrated on Day 0. Thecalibration stability is checked bytesting 2 control specimens.The calibration stability is 10 days.Note: A recalibration is recommendedwhen reagent lots change, and whenquality control results fall outside therange established. |
{6}------------------------------------------------
{7}------------------------------------------------
9. Standard/Guidance Document Reference
No applicable mandatory performance standards or special controls exist for this device
10. Test Principle:
Arsenazo III [2,7-(bis(2-arsonophenylazo))-1,8-dihydroxynaphtalene-3,6-disulphonic acid], forms in neutral medium a blue complex with calcium. The color intensity is directly proportional to the total calcium concentration.
Performance Characteristics - Analytical Performance 11.
a. Precision/Reproducibility
Precision
The precision of the device was determined in accordance with CLSI EP05-A2 protocol (Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline - Second Edition).
Within-run and total precision results were obtained by performing two runs per day, two measures per run, for 3 levels of samples on 2 instruments during twenty operating days
{8}------------------------------------------------
according to CLSI EP05-A2 protocol. The results are presented in the table below:
Serum
| Level | n | Mean (mg/dL) | Precision % | |
|---|---|---|---|---|
| Within-run CV% | Total CV% | |||
| Level 1 | 80 | 8.28 | 1.1 | 1.7 |
| Level 2 | 80 | 10.32 | 0.5 | 1.4 |
| Level 3 | 80 | 12.96 | 0.5 | 1.0 |
Urine
| Level | n | Mean (mg/dL) | Precision % | |
|---|---|---|---|---|
| Within-run CV% | Total CV% | |||
| Level 1 | 80 | 4.53 | 1.3 | 1.8 |
| Level 2 | 80 | 10.89 | 0.5 | 1.2 |
| Level 3 | 80 | 17.51 | 0.3 | 0.8 |
b. Linearity/assay reportable range
The linearity study of ELITech Clinical Systems CALCIUM ARSENAZO was performed according to CLSI protocol EP06-A (Evaluation of the Linearity of the Measurement of Quantitative Procedures: a Statistical Approach; Approved Guideline).
Serum:
The linearity of ELITech Clinical Systems CALCIUM ARSENAZO was studied by mixing a sample with high value (15.35 mg/dL) and a sample with low value (4.94 mg/dL) to obtain 11 levels with equidistant concentrations and then measuring the Calcium concentration of each of the 11 levels using ECS Calcium Arsenazo reagent.
From this study, a measuring range from 5.00 - 15.00 mg/dL has been determined.
Urine:
The linearity of ELITech Clinical Systems CALCIUM ARSENAZO was studied by mixing a sample with high value (18.60 mg/dL) and a sample with low value (1.45 mg/dL) to obtain 11 levels with equidistant concentrations and then measuring the Calcium concentration of each of the 11 levels using ECS Calcium Arsenazo reagent.
From this study, a measuring range from 1.50 - 18.00 mg/dL has been determined.
Auto-dilution 1 to 5 allows the use of the ELITech Clinical Systems CALCIUM ARSENAZO with analyte activities up to 90.00 mg/dL.
c. Traceability
For calibration, a multi-parametric calibrator, most recently cleared under K132399, named ELITech Clinical Systems ELICAL 2 (manufactured by ELITech Clinical Systems SAS under product code CALI-0580) must be used. Traceability of the assigned value for all constituents in this calibrator, including the calcium value assigned to calibrate ELITech Clinical Systems CALCIUM ARSENAZO, is included in its labeling. Traceability for calcium is to NIST SRM 956c Quality Control Materials.
{9}------------------------------------------------
d. Stability
On board stability:
This evaluates the period of time during which correct measurements are obtained after installation of a new vial on board.
At least 3 levels of sample (high/medium/low) are tested in duplicate at Day 0 (D0).
At regular intervals, the three (3) concentration levels are analyzed in duplicate, until the deviations from the results at DO are higher than acceptance criteria or for at least 30 days. During this period, the reagents are stored on the analyzer (vial open).
This study was performed on one (1) lot of ELITech Clinical Systems CALCIUM ARSENAZO reagent on ELITech Clinical Systems Selectra Pro M Analyzer. Results indicate the on-board stability of the reagent is 28 days.
Real-time stability:
The shelf-life of ELITech Clinical Systems CALCIUM ARSENAZO reagent has been followed in real time for 24 months at 2-8°C on 3 different batches.
e. Detection limit
Determined according to CLSI protocol EP17-A (Protocols for Determination of Limits of Detection and Limits of Quantification; Approved Guideline).
Serum
Limit of Detection:
The limit of Detection was obtained from 15 measurements of 4 samples prepared from 4 patient samples measured using ELITech Clinical Systems CALCIUM ARSENAZO and diluted with NaCl 0.9% to obtain a concentration of approximately 5 mg/dL.
The data are not Gaussian, so LoD= LoB + Dsg (where Ds & is determined by calculating the median minus the 50 percentile of the low concentration sample distribution).
Limit of Detection = 0.04 mg/dL.
Limit of Quantification:
The limit of Quantification was obtained from 15 measurements of 4 samples prepared from 4 patient samples measured using ELITech Clinical Systems CALCIUM ARSENAZO and diluted with NaCl 0.9% to obtain a concentration of 5.0 mg/dL.
Acceptance criteria: The acceptable Total Error for the determination Limit of Quantification is ≤ 0.32 mg/dL. If the confidence Interval is within the acceptable total error limits, then the Limit of Quantification is acceptable. The value must be equal or higher than the Limit of Detection.
Limit of Quantification = 5.00 mg/dL.
Urine
Limit of Detection:
The limit of Detection was obtained from 15 measurements of 4 samples prepared from 4 patient samples measured using ELITech Clinical Systems CALCIUM ARSENAZO and diluted with NaCl 0.9% to obtain a concentration of 0.40 mg/dL.
{10}------------------------------------------------
The data are not Gaussian, so LoD= LoB + Dsg (where Dsg is determined by calculating the median minus the 5th percentile of the low concentration sample distribution).
Limit of Detection = 0.15 mg/dL.
Limit of Quantification
The limit of Quantification was obtained from 15 measurements of 4 samples prepared from 4 patient samples measured using ELITech Clinical Systems CALCIUM ARSENAZO and diluted with NaCI 0.9% to obtain a concentration of 1.50 mg/dL.
Limit of Quantification =1.50 mg/dL.
f. Interference/analytical specificity
Serum
Interferences due to unconjugated bilirubin, conjugated bilirubin, hemoglobin, triglycerides, magnesium, ascorbic acid, acetylsalicylic acid and acetaminophen were investigated following the recommended sample levels in CLSI EP07-A2 protocol (Interference Testing in Clinical Chemistry; Approved Guideline - Second Edition).
For each potential interferent tested, 2 serum sample pools at two calcium levels close to those specified in Appendix B of EP7-A2 were prepared:
-1 pool: low concentration at nominal 8.00 mq/dL
-200 pool: high concentration at nominal 12.00 mg/dL
-200 pool: high concentration at nominal 12.00 mg/dL
Aliquots of each of the serum sample pools were spiked with increasing interferent concentration. Test ranges covered at least the interferent level specified in Appendix D of EP7-A2. Thus, there were two series of interferent spike for each potential interferent tested. A control sample was prepared from the sample pool diluted in the appropriate diluent.
| Interferent | Test range | Number of differentconcentrations tested |
|---|---|---|
| Unconjugated bilirubin | up to 30.0 mg/dL | 7 |
| Conjugated bilirubin | up to 29.5 mg/dL | 7 |
| Hemoglobin | up to 500 mg/dL | 9 |
| Triglycerides | up to 3172 mg/dL | 8 |
| Magnesium | up to 12.2 mg/dL | 8 |
| Ascorbic acid | up to 20 mg/dL | 7 |
| Acetylsalicylic Acid | up to 200 mg/dL | 7 |
| Acetaminophen | up to 30 mg/dL | 7 |
Two (2) levels of control (Serum control Level 1 (ELITROL I) and Serum control Level 2 (ELITROL II)) were tested to check the calibration.
For both sample pools for each interferent, each point was measured in triplicate per run. Acceptance criteria: an accepted bias of ±10% in sample pools with low (8.00 mg/dL) or high (12.00 mg/dL) nominal concentration.
The results of testing interferences are the following:
- i Concentration up to 30.0 mg/dL unconjugated bilirubin, 29.5 mg/dL conjugated bilirubin, 500 mg/dL hemoglobin, 1726 mg/dL triglycerides, 12.0 mg/dL magnesium, 20.0 mg/dL ascorbic acid, 200 mg/dL acetylsalicylic acid and 30 mg/dL acetaminophen do not show any significant interference for each substance.
- । In very rare cases, monoclonal gammopathies (multiple myeloma), in particular IgM
{11}------------------------------------------------
type (Waldenstrom's macroglobulinemia) can cause unreliable results.
The following statement will also be included in the labeling:
Other compounds may interfere. Users should refer to the three following literature references:
-Young, D. S., Effects of preanalytical variables on clinical laboratory tests, 200 Ed., AACC Press, (1997).
- Young, D. S., Effects of drugs on clinical laboratory tests, 4th Ed., AACC Press, (1995). -Berth, M. & Delanghe, J. Protein precipitation as a possible important pitfall in the clinical chemistry analysis of blood samples containing monoclonal immunoglobulins: 2 case reports and a review of literature, Acta Clin Belg., (2004), 59, 263.
Urine
Interferences due to Conjugated bilirubin, Hemoglobin, Ascorbic acid, Urea, Uric Acid, Magnesium, and pH were investigated following the recommended sample levels in CLSI EP07-A2 protocol (Interference Testing in Clinical Chemistry; Approved Guideline -Second Edition).
For each potential interferent tested, 2 urine sample pools at two calcium levels close to those specified in Appendix B of EP7-A2 were prepared:
-1 $ pool: low concentration at nominal 4.00 mg/dL
-200 pool: high concentration at nominal 16.00 mg/dL
Aliquots of each of the serum sample pools were spiked with increasing interferent concentration. Test ranges covered at least the interferent level specified in Appendix D of EP7-A2. Thus, there were two series of interferent spike for each potential interferent tested. A control sample was prepared from the sample pool diluted in the appropriate diluent.
| Interferent | Test range | Number of differentconcentrations tested |
|---|---|---|
| Conjugated bilirubin | up to 29.5 mg/dL | 7 |
| Hemoglobin | up to 500 mg/dL | 9 |
| Ascorbic acid | up to 20 mg/dL | 7 |
| Urea | up to 5000 mg/dL | 6 |
| Uric Acid | up to 100 mg/dL | 6 |
| Magnesium | up to 10 mg/dL | 8 |
| pH | 2.5 to 12.0 | 7 |
Two (2) levels of control (Serum control Level 1 (ELITROL I) and Serum control Level 2 (ELITROL II)) were tested to check the calibration.
For both sample pools for each interferent, each point was measured in triplicate per run. Acceptance criteria: an accepted bias of ±10% in sample pools with low (4.00 mg/dL) or high (16.00 mg/dL) nominal concentration.
The results of testing interferences are the following:
- Concentration up to 29.5 mg/dL conjugated bilirubin, 500 mg/dL hemoglobin, 10.0 mg/dL magnesium, 20.0 mg/dL ascorbic acid, 5000 mg/dL urea, 100 mg/dL uric acid, and pH values ranging between 2.5 and 6.0 do not show any significant interference for each substance.
{12}------------------------------------------------
The following statement will also be included in the labeling:
Other compounds may interfere. Users should refer to the two following literature references: -Young, D. S., Effects of preanalytical variables on clinical laboratory tests, 200 Ed., AACC Press, (1997). -Young, D. S., Effects of drugs on clinical laboratory tests, 40 Ed., AACC Press, (1995).
11. Performance Characteristics - Comparison Studies
a. Method comparison
Serum
A correlation study was performed between ELITech Clinical Systems CALCIUM ARSENAZO reagent on a Selectra ProM Analyzer and ABX Pentra Calcium AS CP reagent on a ABX Pentra analyzer according to CLSI EP09-A2 protocol (Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline - Second edition).
This study was performed using 106 serum patient samples from 5.07 to 14.79 mg/dL over a span of 5 days.
Regression analysis of the results yielded the following: y = 0.949 x + 0.41 mg/dL. r = 0.993 r² = 0.986 Standard error of the estimate Sy.x = 0.29 mg/dL.
Urine
A correlation study was performed between ELITech Clinical Systems CALCIUM ARSENAZO reagent on a Selectra ProM Analyzer and ABX Pentra Calcium AS CP reagent on a ABX Pentra analyzer according to CLSI EP09-A2 protocol (Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline - Second edition)
This study was performed using 52 urine patient samples from 1.50 to 17.14 mg/dL over a span of 5 days.
Regression analysis of the results yielded the following: y = 0.936 x + 0.20 mg/dL r = 0.995 r2 = 0.990 Standard error of the estimate Sy.x = 0.39 mg/dL
b. Evaluation of Accuracy: Matrix Effect
63 paired serum and plasma patient specimens (in lithium heparin samples, ranqing from 5.19 to 14.38 mg/dL), were tested on ELITech Clinical Systems Selectra ProM Analyzer according to CLSI protocol EP09-A2 (Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline - Second edition).
Regression analysis of the results vielded the following:
y = 0.976x + 0.26 mg/dL r = 1.000 r² = 0.993
{13}------------------------------------------------
Standard error of the estimate Sy.x = 0.19 mg/dL
c. Expected values/Reference Range
As indicated in the instructions for use for ELITech Clinical Systems CALCIUM ARSENAZO, each laboratory should establish and maintain its own reference values. The values given are used as guidelines only.
Serum/ Plasma-:
8.6 - 10.3 mg/dL 2.15 - 2.57 mmol/L
Urine (for a urinary volume of 1.5 L per day) : 100 – 300 mg/24h 2.50 – 7.50 mmol/24h
Calcemia is always interpreted according to the plasmatic protein rates.
These reference values are from:
Wu, A.H.B., Tietz Clinical guide to laboratory tests, 4 th Ed., (W.B. Saunders), (2006), 684.
2 Endres D.B., Rude R.K., Disorders of Bone, Tietz Fundamentals of Clinical Chemistry, 6th ED., Burtis, C.A. & Ashwood, E.R., Bruns.D.E., (Saunders), (2008), 711.
d. Clinical Studies:
Not applicable
e. Clinical Cut-off:
Not applicable
12. Conclusion
The information on the principle and performance of our device that is contained in this premarket notification is complete and supports a decision that our device is substantially equivalent to the predicate device.
§ 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.