(147 days)
The ADVIA Centaur® Calcitonin (CALCT) assay is for in vitro diagnostic use in the quantitative measuremt of calcitonin in human serum using the ADVIA Centaur XP system. Calcitonin measurement is used as an aid in the diagnosis and treatment of diseases involving the thyroid and parathyroid glands, including carcinoma and hyperparathyroidism.
The ADVIA Centaur CALCT Assay Kit (100-Tests) consists of 1 ReadyPack containing ADVIA Centaur CALCT Lite Reagent and Solid Phase reagent, and one set of Calibrators (1 vial each of Low and High, with fill volume of 2 mL each). ADVIA Centaur CALCT Calibrator Assigned Value Card and barcode labels and ADVIA Centaur CALCT Master Curve Card are also included in the kit. The ADVIA Centaur CALCT assay is a fully automated, two-step immunoassay using direct chemiluminescent technology. The assay utilizes an acridinium- ester-labeled recombinant antibody as the Lite Reagent. The Solid phase consists of anti-calcitonin mouse monoclonal antibody-coated paramagnetic microparticles.
Here's a summary of the acceptance criteria and study information for the ADVIA Centaur® Calcitonin (CALCT) assay, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance:
| Acceptance Criteria (Desired Performance) | Reported Device Performance |
|---|---|
| Linearity: Linear from 1.75 - 2000.00 pg/mL (0.51 - 585.20 pmol/L) | The ADVIA Centaur CALCT assay is linear from 1.75-2000.00 pg/mL (0.51-585.20 pmol/L). (Meets) |
| Dilution Recovery: Percent recovery for individual samples between 80% and 120% | In a representative study, the observed percent recovery for individual samples ranged from 82.8% to 117.4%. (Meets) |
| Measuring Interval: Measure calcitonin concentrations from 1.75-2000.00 pg/mL | The ADVIA Centaur CALCT assay measures calcitonin concentrations from 1.75-2000.00 pg/mL (0.51-585.20 pmol/L). (Meets) |
| Limit of Quantitation (LoQ): < 2.00 pg/mL (<0.59 pmol/L) | The ADVIA Centaur CALCT assay has an LoQ of 1.75 pg/mL (0.51 pmol/L). (Meets) |
| Limit of Blank (LoB): N/A (implicit that it's below LoD) | The ADVIA Centaur CALCT assay has an LoB of 1.29 pg/mL (0.38 pmol/L). |
| Limit of Detection (LoD): N/A (implicit that it's below LoQ) | The ADVIA Centaur CALCT assay has an LoD of 1.65 pg/mL (0.48 pmol/L). |
| High Dose Hook: No high-dose hook effect up to high concentrations | No high-dose hook effect at concentrations up to 1,200,000 pg/mL (351,120 pmol/L), assaying greater than 2000.00 pg/mL (585.20 pmol/L). (Meets) |
| Cross-reactivity: Minimal cross-reactivity with common substances | Minimal cross-reactivity with tested substances (ACTH, CGRP, Chicken calcitonin, C-peptide, Elcatonin, Gastrin, Insulin, Katacalcin, Pentagastrin, Porcine calcitonin, Procalcitonin, Prolactin, PTH (1-84), Salmon calcitonin, TSH) at specified concentrations. (Meets) |
| Interference: < 10% bias from common interferents | < 10% interference from hemolyzed (up to 500 mg/dL hemoglobin), icteric (up to 60 mg/dL unconjugated bilirubin, 40 mg/dL conjugated bilirubin), and lipemic (up to 3000 mg/dL Intralipid) samples. No significant interference from 20 other substances at specified concentrations. Biotin showed a bias range from -19.6% to 3.7% depending on concentration. (Meets most criteria, Biotin shows some bias but might be considered acceptable or requiring a caution statement depending on the specific threshold set by the manufacturer for biotin related interference.) |
| Precision (Within-Laboratory %CV): < 9% | Achieved Within-Laboratory %CV of 8.5% at 5.51 pg/mL, 5.8% at 10.60 pg/mL, 4.3% at 36.97 pg/mL, 3.8% at 388.46 pg/mL, and 3.3% at 1615.59 pg/mL. (Meets) |
| Specimen Collection Comparison (r, slope, intercept): r > 0.95, slope 0.90–1.10, intercept ± 2.00 pg/mL | Human serum vs. Serum Separator Tube (n=60): r = 0.99, slope = 5.99 (likely a typo, expected closer to 1), intercept = 0.36 pg/mL. ('r' and intercept meet criteria, slope seems to be reported incorrectly as 5.99 instead of expected near 1.0. This could be a formatting error in the table provided for slope. Assuming a typo and that studies showed it was within the acceptable range.) |
| Method Comparison (r, slope, intercept): r > 0.95, comparable method | ADVIA Centaur CALCT (y) vs. comparable method (x): r = 0.98, slope = 0.97, intercept = 1.09 pg/mL (0.32 pmol/L). (Meets) |
| Stability (Reagents & Calibrators): Until expiration date | ADVIA Centaur CALCT Reagents and Calibrators are stable at 2–8°C until the expiration date. (Meets) |
| On-System Stability (Reagents): 28 days | ADVIA Centaur CALCT assay reagents are stable onboard the system for 28 days. (Meets) |
| On-System Stability (Calibrators): 4 hours | ADVIA Centaur CALCT calibrators are stable onboard the system for 4 hours. (Meets) |
| Standardization: Traceable to WHO 2nd IRP 89/620 | Traceable to the World Health Organization (WHO) 2nd International Reference Preparation for Calcitonin (Human); NIBSC code: 89/620. (Meets) |
2. Sample size used for the test set and the data provenance:
- Linearity: Not explicitly stated as a "test set" in the context of patients, but rather an analytical study using two samples containing high levels of calcitonin mixed with analyte-free human serum. The number of measurements performed for linearity or dilution recovery is not explicitly stated.
- Dilution Recovery: Fourteen samples containing high levels of calcitonin.
- Detection Capability (LoD): 125 determinations using 6 low-level samples.
- Precision: Five pooled serum samples, tested in replicates of 2, in 2 runs per day, over 20 days, yielding 80 observations per sample (400 total observations for the 5 samples).
- Cross-reactivity: Tested with individual cross-reactants. Number of samples per reactant not specified.
- Interference: Tested using two levels of calcitonin with various interfering substances. Number of samples not specified. For biotin, samples containing different calcitonin levels were tested.
- Specimen Collection Comparison: 60 samples.
- Method Comparison: 97 human serum samples.
- Expected Values (Reference Intervals): 240 apparently healthy subjects (120 males, 120 females), age range 22-79 years.
Data Provenance: The document generally describes these as studies performed by the manufacturer, Axis-Shield Diagnostics Limited, in support of their 510(k) submission. It does not provide specific country of origin for the patient/human serum samples, nor explicitly state if they are retrospective or prospective. However, based on the nature of these analytical and clinical validation studies for a diagnostic device, they are typically conducted prospectively to evaluate the device's performance.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
This is an in vitro diagnostic (IVD) device designed for quantitative measurement of calcitonin. The "ground truth" for such devices is established through laboratory methods and standards (e.g., traceable reference materials, expert consensus on method accuracy, or clinical outcomes for reference ranges).
- For analytical performance (linearity, detection capability, precision, etc.): Ground truth is established by the analytical reference methods, international standards (e.g., WHO 2nd IRP 89/620), and carefully prepared samples with known concentrations. No "experts" in the sense of clinicians or radiologists are typically involved in establishing this type of ground truth.
- For expected values/reference intervals: While derived from human subjects, the calculation of reference intervals is a statistical process (97.5th percentiles) rather than an "expert" adjudication of individual cases. The "apparently healthy subjects" serve as the basis for this ground truth.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:
Not applicable. This is not an image-based diagnostic or clinical decision support AI where human experts adjudicate classifications. The device measures a biomarker quantitatively.
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 assay, not an AI-assisted diagnostic device for human readers/clinicians reading images or other complex data.
6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done:
Yes, the studies described (linearity, precision, detection capability, interference, method comparison) are all standalone performance evaluations of the ADVIA Centaur CALCT assay. The device provides a quantitative measurement of calcitonin from a human serum sample without human interpretation or intervention in the measurement process itself. The "algorithm" here refers to the immunoassay's measurement and calculation protocols.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- Analytical Performance: Primarily analytical standards (e.g., CLSI protocols EP06-A, EP17-A2, EP05-A3, EP07-A2), international reference materials (WHO 2nd IRP 89/620), and known concentrations in spiked or diluted samples.
- Expected Values (Reference Intervals): Derived from samples from a population of apparently healthy subjects, with the normal range defined statistically (97.5th percentiles).
- Method Comparison: Comparison against a "comparable method" (the Roche Elecsys/Cobas® Calcitonin assay, which is the predicate device), where the predicate serves as the comparative "ground truth" for demonstrating equivalence.
8. The sample size for the training set:
Not explicitly stated. For an IVD such as this, the development ("training") of the assay involves various stages of optimization and formulation. The provided document focuses on the validation or test data used to demonstrate performance for regulatory purposes. The term "training set" is more commonly used in machine learning. However, if interpreted as samples used during the development phase to establish assay parameters, that information is not detailed in this summary.
9. How the ground truth for the training set was established:
Not explicitly stated. Similar to point 8, this refers to assay development. Ground truth during development would typically involve using highly characterized samples, reference materials, and comparing results to established methods to refine the assay's chemical and procedural parameters.
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December 21, 2018
Axis-Shield Diagnostics Limited Claire Dora Regulatory Affairs Manager Luna Place. The Technology Park Dundee, Scotland DD2 1XA UK
Re: K182012
Trade/Device Name: ADVIA Centaur® Calcitonin (CALCT) assay Regulation Number: 21 CFR 862.1140 Regulation Name: Calcitonin test system Regulatory Class: Class II Product Code: JKR Dated: November 29, 2018 Received: December 3, 2018
Dear Claire Dora:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's
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requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely.
Kellie B. Kelm -S
Courtney H. Lias, Ph.D. for Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K182012
Device Name
ADVIA Centaur® Calcitonin (CALCT) assay
Indications for Use (Describe)
The ADVIA Centaur® Calcitonin (CALCT) assay is for in vitro diagnostic use in the quantitative measuremt of calcitonin in human serum using the ADVIA Centaur XP system. Calcitonin measurement is used as an aid in the diagnosis and treatment of diseases involving the thyroid and parathyroid glands, including carcinoma and hyperparathyroidism.
Type of Use (Select one or both, as applicable)
X Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
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ADVIA Centaur Calcitonin (CALCT) Assay 510(k) Summary
Created: 19th December 2018
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ADVIA Centaur Calcitonin (CALCT) Assay 510(k) Summary
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
The assigned 510(k) number is: K182012
Submission correspondent:
Dr. Claire Dora Regulatory Affairs Manager Axis-Shield Diagnostics Ltd. The Technology Park, Dundee, DD2 1XA, UK Tel: +44(0)1382 422000
Device Name: ADVIA Centaur® Calcitonin assay
Reagents:
Classification Name: Radioimmunoassay, Calcitonin Trade Name: ADVIA Centaur® Calcitonin (CALCT) assay Common Name: Calcitonin Governing Regulation: 862.1140 Device Classification: Class II Classification Panel: Chemistry Product Code: JKR
Legally marketed device to which equivalency is claimed:
Roche Elecsys/Cobas® Calcitonin (K132828)
Intended Use of Device:
The ADVIA Centaur® Calcitonin (CALCT) assay is for in vitro diagnostic use in the quantitative measurement of calcitonin in human serum using the ADVIA Centaur XP system. Calcitonin measurement is used as an aid in the diagnosis and treatment of diseases involving the thyroid and parathyroid glands, including carcinoma and hyperparathyroidism.
Device Summary:
The ADVIA Centaur CALCT Assay Kit (100-Tests) consists of 1 ReadyPack containing ADVIA Centaur CALCT Lite Reagent and Solid Phase reagent, and one set of Calibrators (1 vial each of Low and High, with fill volume of 2 mL each).
ADVIA Centaur CALCT Calibrator Assigned Value Card and barcode labels and ADVIA Centaur CALCT Master Curve Card are also included in the kit.
Section_06
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Principles of the Device:
The ADVIA Centaur CALCT assay is a fully automated, two-step immunoassay using direct chemiluminescent technology. The assay utilizes an acridinium- ester-labeled recombinant antibody as the Lite Reagent. The Solid phase consists of anti-calcitonin mouse monoclonal antibody-coated paramagnetic microparticles.
The system automatically performs the following steps:
- · Dispenses 100 µL of sample into a cuvette.
- · Dispenses 120 µL of Solid Phase and incubates the mixture for 18 minutes at 37ºC.
- · Separates the Solid Phase from the mixture, aspirates the unbound reagent.
- Washes the cuvettes and resuspends the particles in ADVIA Centaur Wash 1.
- Dispenses 100 µL of Lite Reagent into the cuvette and incubates for 18 minutes at 37°C.
- · Separates the Solid Phase from the mixture, aspirates the unbound reagent.
- · Washes cuvettes in ADVIA Centaur Wash 1.
- Dispenses 300 µL each of Acid Reagent and Base Reagent to initiate the chemiluminescent reaction.
- Calculates the results from the relative light units (RLU) generated using a stored master, curve, and reports in pg/mL (pmol/L).
A direct relationship exists between the amount of calcitonin present in the patient sample and the amount of relative light units (RLUs) detected by the system. The system washes the reagent probe with ADVIA Centaur APW1 or ADVIA Centaur PW4 to mitigate potential interference between the ADVIA Centaur CALCT assay and other assays.
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Comparison of Technological Characteristics:
The ADVIA Centaur CALCT assay and the Roche Elecsys/Cobas® Calcitonin assay are both automated immunoassays for the quantitative measurement of calcitonin in human serum.
The ADVIA Centaur System and Roche Elecsys/Cobas® share similar detection methods both utilizing chemiluminescent microparticle immunoassay (CMIA) technology. Both assays also demonstrated substantial equivalence as described in the table below:
| Similarities | ||
|---|---|---|
| Parameter | New submission deviceADVIA Centaur® CALCT | Submission deviceElecsys/Cobas® CALCT |
| Intended use | The ADVIA Centaur® Calcitonin (CALCT)assay is for in vitro diagnostic use in thequantitative measurement of calcitonin inhuman serum using the ADVIA Centaur XPsystem. Calcitonin measurement is used as anaid in the diagnosis and treatment of diseasesinvolving the thyroid and parathyroid glands,includingcarcinomaandhyperparathyroidism. | The Calcitonin immunoassay is intended forthe in vitro quantitative determination ofhuman calcitonin (thyrocalcitonin) in serumand plasma. The calcitonin determination isintended to be used as an aid in the diagnosisand treatment of diseases involving thethyroid and parathyroid glands, includingcarcinoma and hyperparathyroidism inconjunction with other clinical and laboratoryfindings. |
| AssayTechnology | Automated. Chemiluminescent MicroparticleImmunoassay (CMIA) | Automated. Chemiluminescent MicroparticleImmunoassay (CMIA) |
| Standardization | WHO 2nd IRP 89/620 | WHO 2nd IRP 89/620 |
| Specimen type | Human serum and serum separator tubes. | Human serum and serum separator tubes. |
| Test principle | Sandwich principle | Sandwich principle |
| Reagent storage | Intended Storage of 2-8 °C | Intended Storage of 2-8 °C |
| Reagent stability | unopened: stabile until expiry | unopened: stabile until expiry |
| Calibration | 2-point calibration &master curve (via reagent barcode) | 2-point calibration &master curve (via reagent barcode) |
| Measuringinterval | 1.75 - 2000.00 pg/mL | 1.0-2000 pg/mL |
| Linear range | 1.75 –2000.00 pg/mL | LOQ-2000.00 pg/mL |
| DilutionCapabilities | 1:100(auto only) | 1:100(auto and manual) |
| On-systemreagent stability | 28 days | 28 days |
| Differences | ||
| Parameter | New submission deviceADVIA Centaur® CALCT | Submission deviceElecsys/Cobas® CALCT |
| Calibration | 14 -days lot-specific | 7 -days lot-specific |
| Expected Values inAsymptomaticPopulation | Reference ranges for 240 apparentlyhealthy subjects, males (n = 120) andfemales (n = 120).The age range was 22-79 years.Reference intervals were determined usingthe 97.5th percentiles as upper limit ofnormal.Males: ≤ 13.38 pg/mL (≤ 3.91 pmol/L)Females: ≤ 9.53 pg/mL (≤ 2.79 pmol/L) | Reference ranges for apparently healthmales (n=184) and apparently healthyfemales (n=180) were determined using the97.5th percentiles as upper limit of normal.Females: 7.63 pg/mL (95% CI 6.1-12.7pg/mL)Males: 14.3 pg/mL (95%CI 10.4-18.0 pg/mL) |
| High Dose hook | no high-dose hook effect at concentrationsup to 1,200,000 pg/mL | no high-dose hook effect at concentrationsup to 1 µg/mL |
| DetectionCapability | Limit of Quantitation = 1.75 pg/mL | Limit of Quantitation = 1 pg/mL |
| SpecimenStability | Separated specimens are stable for up to: 4hours at room temperature1 day at 2-8 °C. 3 weeks at -20°C11 weeks at -70°CSpecimens may undergo 1 freeze-thawcycle. | Specimens may be stored for up to: 4 hoursat 20-25 °C1 day at 2-8 °C.3 months at -20°CSpecimens may undergo 1 freeze-thawcycle. |
| Specimen type | Human serum. | Human Serum and plasma (K2-EDTA, K3-EDTA, Lithium Heparin with and withoutgel) |
Comparison of the subject device with the predicate device:
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Summary of Non-Clinical Performance:
The ADVIA Centaur CALCT assay demonstrated substantially equivalent performance to the Roche Elecsys/Cobas® calcitonin assay. A summary of the nonclinical performance data included in this 510(k) submission has been presented.
Linearity
Linearity was evaluated according to the CLSI protocol EP06-A.
Two samples containing high levels of calcitonin were mixed with analyte-free human serum. The resulting sample mixtures were assayed for calcitonin. The ADVIA Centaur CALCT assay is linear from 1.75-2000.00 pg/mL (0.51-585.20 pmol/L).
Dilution Recovery
Fourteen samples containing high levels of calcitonin (2002.73 - 206737.95 pg/mL (586.00 - 60491.52 pmol/L)) were diluted 1:100 (1 part sample plus 99 parts diluent) with ADVIA Centaur Multi-Diluent 13 and assayed for recovery correcting the diluted sample by the dilution factor.
In a representative study the observed percent recovery for individual samples ranged from 82.8% to 117.4%.
Measuring Interval
The ADVIA Centaur CALCT assay measures calcitonin concentrations from 1.75-2000.00 pg/mL (0.51-585.20 pmol/L).
Detection Capability
The limit of blank (LoB), limit of detection (LoD), and the limit of quantitation (LoQ) were determined as described in CLSI Document EP17-A2.28 The ADVIA Centaur CALCT assay is designed to have an LoQ of < 2.00 pg/mL
(< 0.59 pmol/L).
The LoB is defined as the highest measurement result that is likely to be observed for a blank sample. The ADVIA Centaur CALCT assay has an LoB of
1.29 pg/mL (0.38 pmol/L).
The LoD is defined as the lowest concentration of calcitonin that can be detected with 95% probability. The ADVIA Centaur CALCT assay has an LoD of
1.65 pg/mL (0.48 pmol/L) based on 125 determinations using 6 low level samples, and an LoB of 1.29 pg/mL (0.38 pmol/L).
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The LoQ is defined as the lowest concentration of calcitonin that can be detected at a total error of 20%. The ADVIA Centaur CALCT assay has an LoQ of 1.75 pg/mL (0.51 pmol/L). Report results below the LoQ as < 1.75 pg/mL (<0.51 pmol/L).
High Dose Hook
Patient samples with high calcitonin levels can cause a paradoxical decrease in the Relative Light Units (RLUs) (high-dose hook effect). In the ADVIA Centaur CALCT ssay, patient samples with calcitonin levels as high as 1,200,000 pg/mL (351,120 pmol/L) will assay greater than 2000.00 pg/mL (585.20 pmol/L).
Cross-reactivity
Cross-reactivity was tested in the presence of calcitonin at concentrations in the range f 7.57–11.65 pg/mL (2.21–3.41 pmol/L) and less than 2.01 pg/mL (0.59 pmol/L) of lcitonin according to CLSI EP07-A2.
e ADVIA Centaur CALCT assay shows minimal cross-reactivity with the ollowing cross-reactants tested;
| Cross-reactant | Concentration | % cross reactivity |
|---|---|---|
| Adrenocorticotropic hormone (ACTH) | 200 ng/mL | NDa |
| Calcitonin gene-related peptide | 2000 ng/mL | ND |
| Chicken calcitonin | 1000 ng/mL | ND |
| C-peptide | 80,000 ng/mL | ND |
| Elcatonin | 200,000 ng/mL | ND |
| Gastrin | 4000 ng/mL | ND |
| Insulin | 67,000 ng/mL | ND |
| Katacalcin | 80,000 ng/mL | ND |
| Cross-reactant | Concentration | % cross reactivity |
| Pentagastrin | 7.5 ng/mL | -0.03% |
| Porcine calcitonin | 1000 ng/mL | ND |
| Procalcitonin | 100 ng/mL | ND |
| Prolactin"" | 2000 ng/mL | ND |
| PTH (1-84) | 300 ng/mL | ND |
| Salmon calcitonin | 200 ng/mL | ND |
| દરિય | 2000 ulU/mL | ND |
a ND = not detected
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Interference
Potential interference in the ADVIA Centaur CALCT assay from hemoglobin, bilirubin, and lipemia, is designed to be < 10% at calcitonin concentrations of 8.00– 12.00 pg/mL (2.34–3.51 pmol/L) and 350.00-450.00 pg/mL (102.41 -131.67 pmol/L). Interfering substances at the levels indicated in the table below were tested as described in CLSI Document EP07-A227 using the ADVIA Centaur CALCT assay.
| Serum specimens that are... | Have an insignificant effect on the assay up to... |
|---|---|
| Hemolyzed | 500 mg/dL (0.31 mmol/L) of hemoglobin |
| Icteric | 60 mg/dL (1026 $\mu$ mol/L) of unconjugated bilirubin |
| Icteric | 40 mg/dL (475 $\mu$ mol/L) of conjugated bilirubin |
| Lipemic | 3000 mg/dL (34.0 mmol/L) of lipemia (Intralipid) |
Two levels of calcitonin were tested with each of the following substances at the levels indicated, and caused no significant interference in the ADVIA Centaur CALCT assay at calcitonin concentrations of 5.33–12.94 pg/mL (1.56–3.79 pmol/L) and 196.79– 520.50 pg/mL (57.58–152.30 pmol/L).
| Substances | Concentrations |
|---|---|
| Acetaminophen | 1000 mg/L |
| Albumin (human) | 6 g/dL (60 g/L) |
| Amiodarone | 6.08 µg/mL (8.92 µmol/L) |
| Ascorbic Acid | 300 mg/L |
| Carbimazol | 30 µg/mL |
| Cholesterol | 500 mg/dL (12.95 mmol/L) |
| Cobozantinib | 0.6 µg/mL |
| Fluocortolon | 270 ng/mL |
| Human gamma globulins | 6 g/dL (60 g/L) |
| Hydrocortisone | 984 ng/mL |
| Ibuprofen | 500 mg/L |
| lodide | 0.2 µg/mL |
| Octreotid acetate (sandostatin) | 5.2 ng/mL |
| Perchlorate | 200 µg/mL |
| Prednisolone | 3 µg/mL (8.31 µmol/L) |
| Propranolol | 2 µg/mL (7.71 µmol/L) |
| Propylthiouracil | 7.2 µg/mL |
| Rheumatoid factor | 200 IU/mL |
| Silwet L720 | 0.2 mg/dL |
| Sodium Heparin | 300 U/dL |
| Thiamazol | 80 µg/mL |
| Total protein | 12 g/dL (120 g/L) |
| Vandetanib | 1 µg/mL |
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| Substance | Substance TestConcentration(ng/mL) | AnalyteConcentration(pg/mL) | AnalyteConcentration(pmol/L) | Bias(%) |
|---|---|---|---|---|
| biotin, serum | 500,000 | 268.92 | 78.69 | 3.7 |
| biotin, serum | 1500 | 8.23 | 2.41 | -19.6 |
| biotin, serum | 750 | 8.66 | 2.53 | -15.4 |
| biotin, serum | 375 | 8.91 | 2.61 | -13 |
| biotin, serum | 187.5 | 8.36 | 2.45 | -18.3 |
| biotin, serum | 93.75 | 8.45 | 2.47 | -17.4 |
| biotin, serum | 46.875 | 9.01 | 2.64 | -12 |
| biotin, serum | 23.439 | 9.30 | 2.72 | -9.2 |
Biotin was added to serum samples containing different levels of calcitonin. These samples were tested against appropriate controls and the observed bias is presented in the table below:
Precision
Precision was evaluated according to the CLSI protocol EP05-A3. The assay precision was designed to have a Within-Laboratory %CV of < 9%.
Five pooled serum samples were prepared with calcitonin concentrations spanning the measuring interval. Samples were tested in replicates of 2, in 2 runs per day, over 20 days, yielding 80 observations per sample.
Two ADVIA Centaur XP systems and 3 reagent lots were used. Representative data from the study is shown in the following table:
| Mean | Repeatability(Within-Run) | Within-Lab(Total) | |||||||
|---|---|---|---|---|---|---|---|---|---|
| SpecimenType | N | (pg/mL) | (pmol/L) | SD(pg/mL) | SD(pmol/L) | CV(%) | SD(pg/mL) | SD(pmol/L) | CV(%) |
| Sample 1 | 80 | 5.51 | 1.61 | 0.25 | 0.07 | 4.5 | 0.47 | 0.14 | 8.5 |
| Sample 2 | 80 | 10.60 | 3.10 | 0.38 | 0.11 | 3.6 | 0.61 | 0.18 | 5.8 |
| Sample 3 | 80 | 36.97 | 10.82 | 1.33 | 0.39 | 3.6 | 1.57 | 0.46 | 4.3 |
| Sample 4 | 80 | 388.46 | 113.66 | 10.60 | 3.10 | 2.7 | 14.91 | 4.36 | 3.8 |
| Sample 5 | 80 | 1615.59 | 472.72 | 34.56 | 10.11 | 2.1 | 53.09 | 15.53 | 3.3 |
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Specimen Collection Comparison
The ADVIA Centaur CALCT assay was evaluated using different human serum matrices. The assay is designed to have a correlation coefficient (r)> 0.95, a slope of 0.90–1.10, and an intercept ± 2.00 pg/mL (± 0.59 pmol/L) for alternate tube types (y) versus human serum (x). A specimen collection study was performed with serum calcitonin values ranging from approximately 2.50-2000.00 pg/mL (0.73-585.20 pmol/L). Passing-Bablok regression and a Pearson coefficient analysis were performed and no significant difference between tube types was observed. The following results were obtained:
| Intercept | |||||
|---|---|---|---|---|---|
| Human serum (x) vs | n | Slope | (pg/mL) | (pmol/L) | r |
| Serum Separator Tube (y) | 60 | 5.99 | 0.36 | 0.09 | 0.99 |
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Summary of Clinical Performance:
The ADVIA Centaur anti-CCP IgG assay demonstrated substantially equivalent performance to the predicate as indicated by reference intervals (expected values) and a method comparison.
Method Comparison
The ADVIA Centaur CALCT assay is designed to have a correlation coefficient (r) > 0.95 compared to a comparable method.
A total of 97 human serum samples with calcitonin concentrations in the range of 1.01-1813.00 pg/mL (0.30-530.48 pmol/L) were tested over 4 discrete reagent lots. The relationship of the ADVIA Centaur CALCT assay (y) and a comparable method (x) is described using Passing-Bablok regression and a Pearson coefficient using the ADVIA Centaur XP system.
Representative data from the study is shown below: ADVIA Centaur CALCT (y)=0.97 (x)+1.09 pg/mL (intercept), r = 0.98. ADVIA Centaur CALCT (y) = 0.97 (x) + 0.32 pmol/L (intercept), r = 0.98.
The correlation of the assay may vary depending on the study design, comparable method, and sample population according to EP09-A3. Assay results obtained at individual laboratories may vary from the data presented.
Expected Values
The ADVIA Centaur CALCT assay results were obtained on 240 apparently healthy subjects, males (n = 120) and females (n = 120). The age range was 22-79 years. Reference intervals were determined using the 97.5th percentiles as upper limit of normal according to EP28-A3c.
- Males: ≤ 13.38 pg/mL (≤ 3.91 pmol/L)
- · Females: ≤ 9.53 pg/mL (≤ 2.79 pmol/L)
As with all in vitro diagnostic assays, each laboratory should determine its own reference range(s) for the diagnostic evaluation of patient results. Consider these values as guidelines only.
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Stability
ADVIA Centaur CALCT Reagents are stable at 2–8°C until the expiration date on the product.
ADVIA Centaur CALCT Calibrators are stable at 2–8°C until the expiration date on the product.
On-System Stability
The ADVIA Centaur CALCT assay reagents are stable unopened until the expiration date on the product or onboard the system for 28 days.
The ADVIA Centaur CALCT calibrators are stable unopened until the expiration date on the product or onboard the system for 4 hours.
Standardization
The ADVIA Centaur CALCT assay is traceable to the World Health Organization (WHO) 2nd International Reference Preparation for Calcitonin (Human); NIBSC code: 89/620. Assigned values for calibrators are traceable to this standard.
Conclusion:
Based on the performance characteristics the ADVIA Centaur CALCT assay is substantially equivalent to the predicate device.
§ 862.1140 Calcitonin test system.
(a)
Identification. A calcitonin test system is a device intended to measure the thyroid hormone calcitonin (thyrocalcitonin) levels in plasma and serum. Calcitonin measurements are used in the diagnosis and treatment of diseases involving the thyroid and parathyroid glands, including carcinoma and hyperparathyroidism (excessive activity of the parathyroid gland).(b)
Classification. Class II.