(190 days)
Not Found
No
The summary describes a standard in vitro diagnostic immunoassay and analyzer. There is no mention of AI or ML in the intended use, device description, or performance studies. The data analysis described is based on standard calibration and measurement of relative light units.
No.
The device is an in vitro diagnostic (IVD) immunoassay designed to quantitatively determine 1,25 dihydroxyvitamin D levels in human samples, which is for assessment of vitamin D sufficiency, not for treating a condition.
Yes
The device is intended for the quantitative determination of 1,25 dihydroxyvitamin in serum and plasma, with results used in the assessment of vitamin D sufficiency. This directly supports medical diagnosis.
No
The device description clearly indicates it is an in vitro diagnostic (IVD) assay that involves chemical reactions and the measurement of a light signal using a photomultiplier. It also includes physical components like control sets and calibration verifiers containing human serum. While software is undoubtedly involved in controlling the LIAISON® XL Analyzer and processing the RLU data, the core of the device is a chemical immunoassay and associated hardware, not software alone.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states it is an "in vitro chemiluminescent immunoassay (CLIA) intended for the quantitative determination of 1,25 dihydroxyvitamin (1,25(OH)2D) in serum, EDTA and Lithium Heparin plasma." This clearly indicates it is used to test samples taken from the human body in vitro (outside the body).
- Purpose: The results are used "in the assessment of vitamin D sufficiency" and "in conjunction with other clinical and laboratory data to assist the clinician in making individual patient management decisions." This demonstrates its role in diagnosing or aiding in the diagnosis of a medical condition (vitamin D sufficiency/deficiency).
- Device Description: The description details the assay method (immunoassay) and the components used to perform the test on biological samples (serum, plasma).
- Control and Calibration Materials: The inclusion of control sets and calibration verifiers, which are also described as "assayed quality control samples" and "assayed quality control materials," further confirms its use in a laboratory setting for diagnostic testing.
- Performance Studies: The performance studies described (Method Comparison, Sample Matrix Comparison, Reference Range, Precision, Linearity, etc.) are typical studies conducted to validate the analytical performance of an IVD.
- Predicate Devices: The listing of predicate devices, which are also IVDs (specifically the DiaSorin 1,25 Dihydroxyvitamin D 1251 RIA), reinforces the classification of this device as an IVD.
All these elements align with the definition of an In Vitro Diagnostic device, which is a medical device intended for use in vitro for the examination of specimens derived from the human body solely or principally for the purpose of providing information concerning a physiological or pathological state, or concerning a congenital abnormality, or to monitor therapeutic measures.
N/A
Intended Use / Indications for Use
The LIAISON® XL 1,25 Dihydroxyvitamin D is an in vitro chemiluminescent immunoassay (CLIA) intended for the quantitative determination of 1,25 dihydroxyvitamin (1,25(OH)2D) in serum, EDTA and Lithium Heparin plasma. Results of the 1,25 Dihydroxyvitamin D are used in the assessment of vitamin D sufficiency. Assay results should be used in conjunction with other clinical and laboratory data to assist the clinician in making individual patient management decisions in adult populations. The test is to be performed on the LIAISON® XL Analyzer.
The LIAISON® XL 1,25 Dihydroxyvitamin D Control Set is intended for use as assayed quality control samples to monitor the performance of the LIAISON® XL 1,25 Dihydroxyvitamin D assay.
The LIAISON® XL 1.25 Dihydroxyvitamin D Calibration Verifiers are assayed quality control materials intended for the quantitative verification of calibration and reportable range of the LIAISON® XL1,25 Dihydroxyvitamin D assay.
Product codes (comma separated list FDA assigned to the subject device)
MRG, JJX
Device Description
The LIAISON® XL 1,25 Dihydroxyvitamin D assay is a modified three-step sandwich assay that uses a recombinant fusion protein for capture of the 1,25 (OH)> D molecule and a murine monoclonal antibody which specifically recognizes the complex formed by the recombinant fusion protein with the 1,25(OH)2 D molecule. Results are determined by a 2 point calibration conversion of the master curve to a working curve. The light signal is measured by a photomultiplier as relative light units (RLU) and is proportional to the concentration of 1,25(OH)> D present in the calibrators, controls or patient samples.
LIAISON® XL 1,25 Dihydroxyvitamin D Control set contains;
- 2 levels controls containing human serum spiked with 1,25 (OH)2 D, and . preservatives; 2 vials each level; lyophilized
The target concentration for control level 1 is 35 pg/mL. The target concentration for control Level 2 is 120 pg/mL.
The range of concentrations of each control is reported on the certificate of analysis provided with each LIAISON® XL 1.25 Dihydroxyvitamin D Control set.
LIAISON® XL 1,25 Dihydroxyvitamin D Calibration Verifier set contains:
- 4 levels containing human serum spiked with 1,25 (OH), D, and preservatives, . 1 vial each level, lyophilized
The target concentration for cal verifier A is 15 pg/mL. The target concentration for cal verifier B is 40 pg/mL. The target concentration for cal verifier C is 80 pg/mL. The target concentration for cal verifier D is 150 pg/mL.
The range of concentrations of each calibration verifier is reported on the certificate of analysis provided with each LIAISON® XL 1,25 Dihydroxyvitamin D Calibration Verifier set.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
adult populations
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Method Comparison: A method comparison study comparing the LIAISON® XL 1,25 Dihydroxyvitamin D assay to the DiaSorin 1.25-Dihydroxyvitamin D 1251 RIA assay was performed on 141 samples following CLSI EP9-A3. Deming regression analyses were performed on the results across the range of the LIAISON® XL 1,25 Dihydroxyvitamin D assay. Key results: slope = 0.973 (95% CI: 0.855 to 1.092), intercept = -1.614 (95% CI: -7.475 to 4.248), R = 0.918.
Sample Matrix Comparison: Fifty-two (52) matched patient sets of serum, SST serum, EDTA plasma, and Lithium Heparin plasma samples were tested to determine if these sample types provide equivalent results on the LIAISON® XL 1,25 Dihydroxyvitamin D assay. Key results:
- Serum vs. SST Serum: Slope = 1.011 (95% CI: 0.99 to 1.03), Intercept = -0.285 (95% CI: -1.08 to 0.83), R^2 = 0.9908.
- Serum vs. EDTA Plasma: Slope = 1.010 (95% CI: 0.98 to 1.04), Intercept = 0.321 (95% CI: -1.15 to 1.64), R^2 = 0.9975.
- Serum vs. Lithium Heparin: Slope = 1.0000 (95% CI: 0.97 to 1.04), Intercept = 0.1000 (95% CI: -1.24 to 1.31), R^2 = 0.9957.
Reference Range: A study was performed with serum samples from 123 apparently healthy adults aged 21-75 years. Key results: Median 1,25 (OH)2 D = 47.8 pg/mL, Observed Range (2.5th to 97.5th Percentile) = 19.9 - 79.3 pg/mL.
Precision: Precision testing was performed following CLSI Guideline EP5-A2. A coded panel comprised of 6 frozen serum samples (2 spiked, 4 native samples), 2 lots of LIAISON® XL 1,25 Dihydroxyvitamin D controls (2 levels) and 2 lots of LIAISON® XL 1,25 Dihydroxyvitamin D Calibration Verifiers were tested. Samples were tested in two replicates per run, 2 runs per day for 20 operating days for a total of 160 replicate results per sample. Key results include %CV for Between-Lot and Total (Across Lots), and Intra-Run and Total (Within-lot) %CV for different samples/controls/calibrators.
Linearity: One serum sample pool was diluted and analyzed. The resulting equation is: Observed 1,25 (OH)2 D = 0.981(Expected) + 0.005; R=0.9994.
High Dose Hook Effect: Testing was conducted up to 5000 pg/mL of 1,25 (OH)2 D. No hook effect was observed.
Recovery Study: Five high concentration serum samples and 5 low concentration serum samples were analyzed. Recovery samples were prepared by mixing defined ratios. Mean Recovery = 94%.
Analytical Specificity - Cross-Reactivity Studies: Controlled studies of potentially cross reacting substances were performed. All listed cross-reactants showed
§ 862.1825 Vitamin D test system.
(a)
Identification. A vitamin D test system is a device intended for use in clinical laboratories for the quantitative determination of 25-hydroxyvitamin D (25-OH-D) and other hydroxylated metabolites of vitamin D in serum or plasma to be used in the assessment of vitamin D sufficiency.(b)
Classification. Class II (special controls). Vitamin D test systems must comply with the following special controls:(1) Labeling in conformance with 21 CFR 809.10 and
(2) Compliance with existing standards of the National Committee on Clinical Laboratory Standards.
0
Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract symbol that resembles a stylized human figure or a bird in flight, composed of three curved lines.
December 10, 2014
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
DIASORIN INC. CAROL DEPOUW REGULATORY AFFAIRS SPECIALIST 1951 NORTHWESTERN AVENUE STILLWATER MN 55082-0285
Re: K141463
Trade/Device Name: LIAISON® XL 1,25 Dihydroxyvitamin D; LIAISON® XL 1,25 Dihydroxyvitamin D Control Set; LIAISON® XL 1.25 Dihydroxyvitamin D Calibration Verifiers Regulation Number: 21 CFR 862.1825 Regulation Name: Vitamin D test system Regulatory Class: II Product Code: MRG, JJX Dated: November 12, 2014 Received: November 13, 2014
Dear Ms. Carol Depouw:
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
1
electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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/ResourcesforYou/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,
Katherine Serrano -S
For : 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
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Indications for Use
510(k) Number (if known) K141463
Device Name
LIAISON® XL 1,25 Dihydroxyvitamin D LIAISON® XL 1,25 Dihydroxyvitamin D Control Set LIAISON® XL 1,25 Dihydroxyvitamin D Calibration Verifiers
Indications for Use (Describe)
The LIAISON® XL 1,25 Dihydroxyvitamin D is an in vitro chemiluminescent immunoassay (CLIA) intended for the quantitative determination of 1,25 dihydroxyvitamin (1,25(OH)2D) in serum, EDTA and Lithium Heparin plasma. Results of the 1,25 Dihydroxyvitamin D are used in the assessment of vitamin D sufficiency. Assay results should be used in conjunction with other clinical and laboratory data to assist the clinician in making individual patient management decisions in adult populations. The test is to be performed on the LIAISON® XL Analyzer.
The LIAISON® XL 1,25 Dihydroxyviamin D Control Set is intended for use as assayed quality control samples to monitor the performance of the LIAISON® XL 1,25 Dihydroxyvitamin D assay.
The LIAISON® XL 1,25 Dihydroxyvitamin D Calibration Verifiers are assayed quality control materials intended for the quantitative verification of calibration and reportable range of the LIAISON® XL1,25 Dihydroxyvitamin D assay.
| 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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510(k) Summary
LIAISON® XL 1,25 Dihydroxyvitamin D LIAISON® XL 1,25 Dihydroxyvitamin D Control Set LIAISON® XL 1,25 Dihydroxyvitamin D Calibration Verifiers
This summary of 510(k) safety and effectiveness information is submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
1. 510(k) Number: K141463
-
- Applicant: Carol A. DePouw DiaSorin Inc. 1951 Northwestern Avenue, Stillwater, MN 55082-0285 Office Number: 651-351-5850; Fax Number: 651-351-5669 Email: carol.depouw@diasorin.com
- Date: May 30, 2014
4. Proprietary and Established Names:
LIAISON® XL 1,25 Dihydroxyvitamin D LIAISON® XL 1,25 Dihydroxyvitamin D Control Set LIAISON® XL 1,25 Dihydroxyvitamin D Calibration Verifiers
5. Requlatorv Information:
LIAISON® XL 1,25 Dihydroxyvitamin D
Requlation Section: 21 CFR 862.1825 Classification: Class II Product Code: MRG Panel: Clinical Chemistry (75)
LIAISON® XL 1,25 Dihydroxyvitamin D Control Set LIAISON® XL 1.25 Dihvdroxvvitamin D Calibration Verifiers
Requlation Section: 21 CFR 862.1660 Classification: Class I, reserved Product Code: JJX Panel: Clinical Chemistry (75)
6. Predicate Devices:
The predicate device used to demonstrate substantial equivalence to the LIAISON® XL 1,25 Dihydroxyvitamin D is the DiaSorin 1,25 Dihydroxyvitamin D 1251 RIA previously cleared under K014030.
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The predicate device used to demonstrate substantial equivalence to the LIAISON® XL 1,25 Dihydroxyvitamin D is the LIAISON® N-TACT® PTH Gen II Control Set previously cleared under K132515.
The predicate device used to demonstrate substantial equivalence to the LIAISON® XL 1,25 Dihydroxyvitamin D Calibration Verifiers is the LIAISON® N-TACT® PTH Gen II Calibration Verifiers previously cleared under K132515.
7. Device Description:
The LIAISON® XL 1,25 Dihydroxyvitamin D assay is a modified three-step sandwich assay that uses a recombinant fusion protein for capture of the 1,25 (OH)> D molecule and a murine monoclonal antibody which specifically recognizes the complex formed by the recombinant fusion protein with the 1,25(OH)2 D molecule. Results are determined by a 2 point calibration conversion of the master curve to a working curve. The light signal is measured by a photomultiplier as relative light units (RLU) and is proportional to the concentration of 1,25(OH)> D present in the calibrators, controls or patient samples.
LIAISON® XL 1,25 Dihydroxyvitamin D Control set contains;
- 2 levels controls containing human serum spiked with 1,25 (OH)2 D, and . preservatives; 2 vials each level; lyophilized
The target concentration for control level 1 is 35 pg/mL. The target concentration for control Level 2 is 120 pg/mL.
The range of concentrations of each control is reported on the certificate of analysis provided with each LIAISON® XL 1.25 Dihydroxyvitamin D Control set.
LIAISON® XL 1,25 Dihydroxyvitamin D Calibration Verifier set contains:
- 4 levels containing human serum spiked with 1,25 (OH), D, and preservatives, . 1 vial each level, lyophilized
The target concentration for cal verifier A is 15 pg/mL. The target concentration for cal verifier B is 40 pg/mL. The target concentration for cal verifier C is 80 pg/mL. The target concentration for cal verifier D is 150 pg/mL.
The range of concentrations of each calibration verifier is reported on the certificate of analysis provided with each LIAISON® XL 1,25 Dihydroxyvitamin D Calibration Verifier set.
8. Intended Use:
The LIAISON® XL 1,25 Dihydroxyvitamin D is an in vitro chemiluminescent immunoassay (CLIA) intended for the quantitative determination of 1,25 dihydroxyvitamin (1,25(OH)» D) in serum, EDTA and Lithium Heparin plasma. Results
5
of the 1,25 Dihydroxyvitamin D are used in the assessment of vitamin D sufficiency. Assay results should be used in conjunction with other clinical and laboratory data to assist the clinician in making individual patient management decisions in adult populations. The test is to be performed on the LIAISON® XL Analyzer.
The LIAISON® XL 1,25 Dihydroxyvitamin D Control Set is intended for use as assayed quality control samples to monitor the performance of the LIAISON® XL 1,25 Dihydroxyvitamin D assay.
The LIAISON® XL 1.25 Dihydroxyvitamin D Calibration Verifiers are assayed quality control materials intended for the quantitative verification of calibration and reportable range of the LIAISON® XL1,25 Dihydroxyvitamin D assay.
9. Indication(s) for Use:
Same as Intended Use
10. Substantial Equivalence Information:
The LIAISON® XL 1,25 Dihydroxyvitamin D, LIAISON® XL 1,25 Dihydroxyvitamin D controls and LIAISON® XL 1,25 Dihydroxyvitamin D Calibration Verifiers are prepackaged reagents for use on an automated clinical chemistry analyzer. The DiaSorin 1,25 Dihydroxyvitamin D 1251 RIA consists of prepackaged reagents for nonautomated manual use. A comparison of the similarities and differences between the devices are provided in the following table:
| Assay Similarities and Differences | ||
|---|---|---|
| Characteristic | New Device | |
| LIAISON® XL 1,25 | ||
| Dihydroxyvitamin D | Predicate Device | |
| 1,25-Dihydroxyvitamin D 125I RIA | ||
| (K014030) | ||
| Intended Use | For in vitro quantitative determination | |
| of 1,25 Dihydroxyvitamin D | For in vitro quantitative determination | |
| of 1,25 Dihydroxyvitamin D | ||
| Measured Analyte | 1,25(OH)2 D | 1,25(OH)2 D |
| Primary extraction | No | Yes |
| Calibration | Two-point calibration | Five-point calibration |
| Calibration interval | 14 days | every run |
| Calibrators | 2 levels | 5 levels |
| Antibody | Mouse monoclonal | Rabbit polyclonal |
| Reagent Storage | in refrigerator @ 2-8°C | Same |
| Measuring range | 5 – 200 pg/mL | 5 – 200 pg/mL |
| Sample Matrix | Serum, SST serum, EDTA Plasma, | |
| and Lithium Heparin | Serum and EDTA Plasma | |
| Sample size | 75 μL | 500 μL |
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| Manufacturers
| Controls | 2 levels | Same |
|---|---|---|
| Reference range | 19.9 – 79.3 pg/mL | 25.1 - 66.1 pg/mL |
| Control Similarities and Differences | ||
|---|---|---|
| Characteristic | New Device | Predicate Device |
| LIAISON® XL 1,25 Dihydroxyvitamin | ||
| D Control Set | LIAISON® N-TACT® PTH Gen II | |
| Control Set (K132515) | ||
| Intended Use | intended for use as assayed quality | |
| control samples to monitor the | ||
| performance of the LIAISON® XL | ||
| 1,25 Dihydroxyvitamin D | intended for use as assayed quality | |
| control samples to monitor the | ||
| accuracy and precision of the | ||
| LIAISON®N-TACT® PTH Gen II | ||
| Storage | Store at 2-8°C until ready to use | Same |
| Levels | 2 levels: lyophilized | |
| Level 1 (approx 35 pg/mL) | ||
| Level 2 (approx 120 pg/mL) | 2 levels: lyophilized | |
| Level 1 (approx 20 pg/mL) | ||
| Level 2 (approx 30 pg/mL) |
| Calibration Verifiers Similarities and Differences | ||
|---|---|---|
| Characteristic | Candidate Device | Predicate Device |
| Characteristic | LIAISON® XL 1,25 Dihydroxyvitamin D | |
| Calibration Verifiers | LIAISON® N-TACT® PTH Gen II | |
| Calibration Verifiers (K132515) | ||
| Intended Use | assayed quality control materials | |
| intended for the quantitative | ||
| verification of calibration and | ||
| reportable range of the LIAISON® | ||
| XL1,25 Dihydroxyvitamin D assay. | assayed quality control materials | |
| intended for the quantitative | ||
| verification of calibration and | ||
| reportable range of the LIAISON® | ||
| N-TACT® PTH Gen II assay | ||
| Storage | 2 to 8°C | Same |
| Levels | 4 levels; lyophilized | |
| Cal Ver A (approx 15 pg/mL) | ||
| Cal Ver B (approx 40 pg/mL) | ||
| Cal Ver C (approx 80 pg/mL) | ||
| Cal Ver D (approx 150 pg/mL) | 4 levels; lyophilized | |
| Cal Ver A (approx 10 pg/mL) | ||
| Cal Ver B (approx 150 pg/mL) | ||
| Cal Ver C (approx 650 pg/mL) | ||
| Cal Ver D (approx 1600 pg/mL) | ||
| Volume | 2.0 mLs | Same |
11. Standard/guidance Document Reference:
- · CLSI Guideline EP5-A2, Evaluation of Precision Performance of Quantitative Measurement Methods;
- CLSI Guideline EP6-A, Evaluation of Linearity of Quantitative Analytical Methods;
- · CLSI Guideline EP7-A2, Interference Testing in Clinical Chemistry;
- · CLSI Guideline EP09-A3 Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guideline
- CLSI Guideline EP17-A2 Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures;
CLSI Guideline EP28-A3, Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory.
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12. Performance Characters:
Method Comparison
A method comparison study comparing the LIAISON® XL 1,25 Dihydroxyvitamin D assay to the DiaSorin 1.25-Dihydroxyvitamin D 1251 RIAassay was performed on 141 samples following CLSI EP9-A3.
Mean results for the 1,25-Dihydroxyvitamin D 1261 RIA assay and the singlicate results for LIAISON® XL 1,25 Dihydroxyvitamin D were plotted. Deming regression analyses were performed on the results across the range of the LIAISON® XL 1,25 Dihydroxyvitamin D assay.
| Deming Regression | |||||
|---|---|---|---|---|---|
| n | slope | 95% CI | intercept | 95% CI | R |
| 141 | 0.973 | 0.855 to 1.092 | -1.614 | -7.475 to 4.248 | 0.918 |
Sample Matrix Comparison
Fifty-two (52) matched patient sets of serum, SST serum, EDTA plasma, and Lithium Heparin plasma samples were tested to determine if these sample types provide equivalent results on the LIAISON® XL 1,25 Dihydroxyvitamin D assay. The following results were obtained:
| Serum vs. | Slope | 95% CI | Intercept pg/mL | 95% CI | R2 |
|---|---|---|---|---|---|
| SST Serum | 1.011 | 0.99 to 1.03 | -0.285 | -1.08 to 0.83 | 0.9908 |
| EDTA Plasma | 1.010 | 0.98 to 1.04 | 0.321 | -1.15 to 1.64 | 0.9975 |
| Lithium Heparin | 1.0000 | 0.97 to 1.04 | 0.1000 | -1.24 to 1.31 | 0.9957 |
Reference Range
It is recommended that each laboratory establish its own range of expected values.
To assess the expected reference range for the LIAISON® XL 1,25 Dihydroxyvitamin D a study was performed with serum samples from 123 apparently healthy adults aged 21 -75 years of age from mixed ethnic backgrounds (48% dark skinned and 52% light skinned). Samples were collected in the winter (48.8%) and summer (51.2%) from subjects with normal Total Calcium, TSH, and PTH values from the northern, central and southern regions of the U.S. Based on the 95% Reference Interval, the following values were established following CLSI guideline C28-A3.
| U.S. Subjects | Median
1,25 (OH)2 D | Observed Range
2.5th to 97.5th Percentile |
|---------------|------------------------|----------------------------------------------|
| N=123 | 47.8 pg/mL | 19.9 - 79.3 pg/mL |
Precision
Precision testing was performed following CLSI Guideline EP5-A2, Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline -Second Edition.
A coded panel comprised of 6 frozen serum samples (2 spiked, 4 native samples) 2 lots of LIAISON® XL 1,25 Dihydroxyvitamin D controls (2 levels) and 2 lots of LIAISON® XL
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1,25 Dihydroxyvitamin D Calibration Verifiers were tested in the study. The precision panel samples and kit controls were tested on two lots of LIAISON® XL 1,25 Dihydroxyvitamin D in two replicates per run, 2 runs per day for 20 operating days for a total of 160 replicate results per sample. The 20 day results are summarized for the combined reagent lot numbers as sample mean 1,25 (OH)> D concentration in pg/mL, standard deviations and coefficient of variation (%CV) for Between lot and Total across lots.
| Sample ID | n | mean
(pg/mL) | Between-Lot | | Total
(Across Lots) | |
|---------------|-----|-----------------|-------------|------|------------------------|------|
| | | | SD | %CV | SD | %CV |
| Kit Control 1 | 160 | 30.9 | 0.84 | 2.7% | 1.16 | 3.8% |
| Kit Control 2 | 160 | 122.9 | 6.09 | 5.0% | 4.36 | 3.6% |
| Prec Serum 1 | 160 | 23.3 | 0.05 | 0.2% | 1.53 | 6.6% |
| Prec Serum 2 | 160 | 38.9 | 0.63 | 1.6% | 2.20 | 5.7% |
| Prec Serum 3 | 160 | 52.7 | 0.64 | 1.2% | 2.65 | 5.0% |
| Prec Serum 4 | 160 | 76.0 | 1.33 | 1.7% | 3.13 | 4.1% |
| Prec Serum 5 | 160 | 137.4 | 1.91 | 1.4% | 6.55 | 4.8% |
| Prec Serum 6 | 160 | 193.4 | 5.53 | 2.9% | 11.34 | 5.9% |
| Cal Ver A | 160 | 13.4 | 0.36 | 2.7% | 0.76 | 5.7% |
| Cal Ver B | 160 | 38.9 | 2.76 | 7.1% | 1.36 | 3.5% |
| Cal Ver C | 160 | 78.4 | 3.37 | 4.3% | 2.82 | 3.6% |
| Cal Ver D | 160 | 153.0 | 1.35 | 0.9% | 5.61 | 3.7% |
The following results were obtained from 1 lot of kit controls and the same 6 serum samples with one kit lot assayed in duplicate in two assays per day over 20 operating days.
| Intra-Run | TOTAL (Within-lot) | ||||
|---|---|---|---|---|---|
| Sample ID | mean | SD | %CV | SD | %CV |
| KC-1 | 30.3 | 0.75 | 2.5% | 1.30 | 4.3% |
| KC-2 | 118.6 | 3.78 | 3.2% | 4.15 | 3.5% |
| PREC-1 | 23.3 | 0.91 | 3.9% | 1.81 | 7.8% |
| PREC-2 | 38.4 | 1.27 | 3.3% | 2.58 | 6.7% |
| PREC-3 | 52.2 | 1.35 | 2.6% | 2.79 | 5.3% |
| PREC-4 | 75.1 | 2.08 | 2.8% | 3.40 | 4.5% |
| PREC-5 | 136.1 | 3.26 | 2.4% | 6.91 | 5.1% |
| PREC-6 | 189.5 | 5.14 | 2.7% | 11.09 | 5.9% |
Linearity
Dilution Linearity:
One serum sample pool was diluted and analyzed by the LIAISON® XL 1,25 Dihydroxyvitamin D assay following CLSI EP6-A. The results were analyzed by regression of Observed 1,25 (OH)> D Concentration versus Expected 1,25 (OH)> D Concentration.
The resulting equation is: Observed 1,25 (OH)2 D = 0.981(Expected) + 0.005;R=0.9994
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High Dose Hook Effect
Testing was conducted to determine if the LIAISON® XL 1,25 Dihydroxyvitamin D assay is susceptible to artificially low results in the presence of very high levels of 1,25 (OH)2 D (Hook Effect). A zero sample was spiked with enough 1,25 (OH)2 D to equal concentrations above the assay measuring range of 200 pg/mL.
No hook effect was observed up to 5000 pg/mL of 1,25 (OH)2 D .
Recovery Study
Five (5) high concentration serum samples and 5 low concentration serum samples were analyzed neat on the LIAISON® XL 1,25 Dihydroxyvitamin D assay. Recovery samples were then prepared by mixing defined ratios of the high and low samples and tested in replicates of 5. The observed values were compared to the expected values to determine the % recovery.
| Samples | Defined
Concentration | Expected
pg/mL | Observed
pg/mL | %
Recovery |
|---------------------|--------------------------|-------------------|-------------------|---------------|
| High Sample 1 (HS1) | 177.4 | | | |
| 2 HS1 : 1 LS1 | | 128.0 | 121.0 | 95% |
| 1 HS1 : 1 LS1 | | 102.6 | 97.3 | 95% |
| 1 HS1 : 2 LS1 | | 77.2 | 73.0 | 95% |
| Low Sample 1 (LS1) | 27.8 | | | |
| High Sample 2 (HS2) | 203.6 | | | |
| 2 HS2 : 1 LS2 | | 151.7 | 141.6 | 93% |
| 1 HS2 : 1 LS2 | | 125.0 | 115.4 | 92% |
| 1 HS2 : 2 LS2 | | 98.2 | 89.8 | 91% |
| Low Sample 2 (LS2) | 46.3 | | | |
| High Sample 3 (HS3) | 181.6 | | | |
| 2 HS3 : 1 LS3 | | 134.2 | 127.0 | 95% |
| 1 HS3 : 1 LS3 | | 109.8 | 101.8 | 93% |
| 1 HS3 : 2 LS3 | | 85.4 | 81.7 | 96% |
| Low Sample 3 (LS3) | 38.0 | | | |
| High Sample 4 (HS4) | 201.6 | | | |
| 2 HS4 : 1 LS4 | | 143.0 | 137.6 | 96% |
| 1 HS4 : 1 LS4 | | 112.9 | 105.4 | 93% |
| 1 HS4 : 2 LS4 | | 82.7 | 77.4 | 94% |
| Low Sample 4 (LS4) | 24.2 | | | |
| High Sample 5 (HS5) | 223.8 | | | |
| 2 HS5 : 1 LS5 | | 158.3 | 148.4 | 94% |
| 1 HS5 : 1 LS5 | | 124.6 | 111.8 | 90% |
| 1 HS5 : 2 LS5 | | 90.8 | 85.1 | 94% |
| Low Sample 5 (LS5) | 25.3 | | | |
| | | | Mean Recovery | 94% |
Analytical Specificity
Cross-Reactivity Studies
CLSI Guideline EP7-A2, Interference Testing in Clinical Chemistry; Approved Guideline; Second Edition.
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Controlled studies of potentially cross reacting substances were performed on the LIAISON® XL 1,25 Dihydroxyvitamin D assay at the concentrations listed below.
| Cross-Reactant | Spiked
Concentration | % Cross
Reactivity |
|-----------------|-------------------------|-----------------------|
| 1,25 (OH)2 D3 | 50 pg/mL | 103.4% |
| 1,25 (OH)2 D2 | 50 pg/mL | 104.8% |
| Zemplar | 100 pg/mL | 113% |
| 25(OH)D3 | 100,000 pg/mL | D levels up to 60 pg/mL showed no interference in the LIAISON® XL 1,25 Dihydroxyvitamin D at the highest concentration for each substance listed below.
| Drug/Substance | Highest Concentration at
which no significant
interference
(≤ ±10%) was observed |
|--------------------------|-------------------------------------------------------------------------------------------|
| Hemoglobin | 300 mg/dL |
| Bilirubin (conjugated) | 40 mg/dL |
| Bilirubin (unconjugated) | 40 mg/dL |
| Triglycerides | 3,000 mg/dL |
| Cholesterol | 400 mg/dL |
| Albumin | 12 g/dL |
| Uric Acid | 20 mg/dL |
| HAMA | 3774 ng/mL |
| Rheumatoid Factor | 7310 IU/mL |
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Controlled studies of potentially interfering exogenous substances performed in serum with 1,25 (OH)2 D levels up to 60 pg/mL showed no interference in the LIAISON® XL 1,25 Dihydroxyvitamin D at the highest concentration for each substance listed below.
| Drug/Substance | Highest Concentration at
which no significant
interference (≤ ±10%) was
observed. |
|----------------------|--------------------------------------------------------------------------------------------|
| Acetaminophen | 20 mg/dL |
| Acetylsalicylic Acid | 65 mg/dL |
| Salicylic Acid | 60 mg/dL |
| Ibuprofen | 50 mg/dL |
| Biotin | 0.1mg/dL |
| Ascorbic Acid | 6 mg/dL |
| Metaprolol | 1.2 mg/dL |
| Propanolol | 0.23 mg/dL |
| Hydrochlorothiazide | 0.6 mg/dL |
| Furosemide | 6 mg/dL |
| Valproic Acid | 57.6 mg/dL |
| Spironolactone | 0.6 µg/mL |
| Nifedipine | 43 µg/dL |
| Verapamil | 216 µg/dL |
| Losartan Potassium | 2.25 µg/mL |
| Valsartan | 11 µg/mL |
| Tetracycline | 15.1 µg/mL |
| Enalapril | 42.4 µg/dL |
| Doxycycline | 34.6 µg/mL |
| Lisinopril | 32.7 µg/dL |
Limit of Blank, Limit of Detection and Limit of Quantitation
The Limit of Blank, Limit of Detection and Limit of Quantitation were determined according to CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline June 2012 - Second Edition.
The following limits were determined with the LIAISON® XL 1,25 Dihydroxyvitamin D Assay:
| LoB | LoD | LoQ |
|---|---|---|
| ≤ 0.35 pg/mL | 0.70 pg/mL | 5.0 pg/mL |
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| Product | Storage Conditions | Claimed stability | |
|---|---|---|---|
| Reagent Integral | Open vial | at 2-8°C | 28 days |
| Binding Agent | Open vial | at 2-8°C | 2 days |
| Calibrators | Open vial - | ||
| Reconstituted | On system/ | ||
| Room temp | 6 hours | ||
| Open vial - | |||
| Reconstituted | 2-8°C | 14 days | |
| Calibration curve | N/A | N/A | 14 days |
| Controls | Open vial - | ||
| Reconstituted | On system/ | ||
| Room temp | 6 hours | ||
| Open vial - | |||
| Reconstituted | 2-8°C | 28 days | |
| Calibration Verifiers | Open vial - | ||
| Reconstituted | On system/ | ||
| Room temp | 6 hours | ||
| Open vial - | |||
| Reconstituted | 2-8°C | 28 days |
Traceability
The LIAISON® XL 1,25 Dihydroxyvitamin D Calibrators, Controls and Calibration Verifiers are traceable to in-house standards prepared from certified reference material 1α. 25 dihvdroxvvitamin D.
Value Assignment
Calibrators
A minimum of 5 vials of each level of calibrator are tested on a minimum of 3 LIAISON® XL Analyzers, in a minimum of 5 assay runs with six replicates per vial resulting in a minimum of 30 individual replicate results per calibrator level for final value assignment.
Controls
A minimum of 10 vials of each level of control are tested on 2 different LIAISON® XL 1.25 Dihvdroxvvitamin D assay kit lots on a minimum of 3 LIAISON® XL Analyzers, in a minimum of 5 assay runs with 4 replicates per vial resulting in a minimum of 40 individual replicate results per control level for final value assignment. Final control ranges are established based on ± 2 Standard Deviations.
Calibration Verifiers
A minimum of 10 vials of each level of calibration verifier are tested on 2 different LIAISON® XL 1,25 Dihydroxyvitamin D assay kit lots on a minimum of 3 LIAISON® XL Analyzers, in a minimum of 5 assay runs with 4 replicates per vial resulting in a minimum of 40 individual replicate results per level for final value assignment. Final calibration verifier ranges are established based on ± 2 Standard Deviations.
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13. Conclusion:
The LIAISON®XL 1,25 Dihydroxyvitamin D is substantially equivalent in principle and
performance to the DiaSorin 1,25 Dihydroxyvitamin D 12°1 RIA. Accuracy was demonstrated by a Method Comparison.
The LIAISON® XL 1,25 Dihydroxyvitamin D Control Set and the LIAISON® XL 1,25 Dihydroxyvitamin D Calibration Verifiers are substantially equivalent in principle and performance to the LIAISON® N-TACT® PTH Gen II Control Set and LIAISON® N-TACT® PTH Gen II Calibration Verifiers, respectively.