(154 days)
The LIAISON® 25 OH Vitamin D Assay uses chemiluminescent immunoassay (CLIA) technology intended for the quantitative determination of 25hydroxyvitamin D (25-OH-D) and other hydroxylated vitamin D metabolites in human serum or plasma to be 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 an adult population
The method for quantitative determination of 25 OH Vitamin D is a direct, competitive chemiluminescence immunoassay (CLIA). Specific antibody to Vitamin D is used for coating magnetic particles (solid phase) and Vitamin D is linked to an isoluminol derivative. During the incubation, 25 OH Vitamin D is dissociated from its binding protein, and competes with labeled Vitamin D for binding sites on the antibody. After the incubation, the unbound material is removed with a wash cycle, Subsequently, the starter reagents are added and a flash chemiluminescent reaction is initiated. The light signal is measured by a photomultiplier as relative light units (RLU) and is inversely proportional to the concentration of 25 OH Vitamin D present in calibrators, controls, or samples.
The provided text describes the LIAISON® 25 OH Vitamin D Assay, a chemiluminescent immunoassay for the quantitative determination of 25-hydroxyvitamin D (25-OH-D) and other hydroxylated vitamin D metabolites in human serum or plasma.
Here's an analysis of the acceptance criteria and study information:
1. Table of Acceptance Criteria and Reported Device Performance
| Parameter | Acceptance Criteria (Implied / Expected) | Reported Device Performance (LIAISON® 25 OH Vitamin D Assay) |
|---|---|---|
| Sensitivity (analytical) | Low | < 2.0 ng/mL (1.7 ng/mL; 1.6 ng/mL; 1.5 ng/mL for 3 lots) |
| Sensitivity (functional) | Low | 7.0 ng/mL |
| Total Precision (%CV) | Low variability | 6% - 13% |
| Recovery (mean) | Close to 100% | 109% ± 18% |
| Linearity | Good correlation (r close to 1) | $y = 0.98x + 4.1; r = 0.98$ |
| Endogenous Substance Interference | No significant interference | No significant interference observed for Bilirubin (30 mg/dL); hemoglobin (250 mg/dL); Cholesterol (125 mg/dL); Triglycerides (1000 mg/dL) |
| Sample Types Equivalence | Equivalence | Serum and EDTA Plasma are equivalent |
| Sample Stability (Temp) | Stable for 5 days at 2°C - 8°C | Equivalent results |
| Sample Stability (Freeze/Thaw) | Stable for up to 5 cycles | Equivalent results |
| Carry-over | No carry-over | No carry-over observed |
| Correlation with Predicate Device | Good correlation | $r = 0.88$ (with DiaSorin RIA method) |
| Reference Range Establishment | Representative range | 9.5 to 52.0 ng/mL (2.5th to 97.5th percentiles) |
2. Sample size used for the test set and the data provenance
The document does not explicitly define a "test set" in the context of a machine learning study. Instead, it describes performance characteristics of an in-vitro diagnostic device:
- Analytical sensitivity: Tested with "three lots of materials."
- Functional sensitivity: Determined from "serial dilutions." (Number of samples not specified).
- Total precision: Not explicitly stated, but "across the range of the assay according to NCCLS guidelines" implies multiple samples and runs.
- Linearity: Not specified, but "$y = 0.98x + 4.1; r = 0.98$" suggests a range of concentrations were tested.
- Endogenous Substance Interference: Likely tested with spiked samples, but the number is not specified.
- Sample Types: "Serum and EDTA plasma matrices" were compared.
- Sample Stability: Involved storing samples at different temperatures and subjecting them to freeze/thaw cycles.
- Carry-over: Tested low concentration samples directly after high concentration samples.
- Correlation with Predicate Device: Not explicitly stated, but "correlated well with the DiaSorin RIA method" implies a comparative study with an unspecified number of samples.
- Reference Range: Established using 98 samples from "apparently healthy normal volunteers."
- Data Provenance: The 98 samples for reference range were "collected in the southwestern United States in late autumn." All data relate to the performance of the assay itself and are considered prospective for the device evaluation.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
Not applicable. This is an in vitro diagnostic device for quantitative determination of a biomarker, not an imaging device or AI for diagnosis that requires expert readers for ground truth. The "ground truth" for the performance characteristics typically refers to established analytical methods, reference materials, or clinical outcomes, rather than expert interpretation of images/data.
4. Adjudication method for the test set
Not applicable, as it's not a reader-based study requiring adjudication. The performance is assessed against analytical standards and comparative methods.
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 tool involving human readers interpreting cases.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the study describes the standalone performance of the LIAISON® 25 OH Vitamin D Assay. The results presented (sensitivity, precision, linearity, etc.) are inherent to the device and its analytical process, without human interpretation as part of the primary measurement. The assay outputs a quantitative value directly.
7. The type of ground truth used
The "ground truth" for evaluating this assay's performance would be:
- Reference Methods/Standards: For analytical sensitivity, linearity, and recovery, results are compared against known concentrations or established reference methods.
- Clinical Samples: For precision, interference, sample type equivalence, and stability, the assay's performance on clinical samples is assessed.
- Predicate Device: For method correlation, the LIAISON® assay's results are compared against the DiaSorin 25-Hydroxyvitamin D 125I RIA predicate device.
- Statistically Derived Normal Ranges: The reference range was established by measuring 98 samples from healthy individuals and calculating percentiles (2.5th to 97.5th).
8. The sample size for the training set
Not applicable in the typical sense for machine learning. This is a traditional immunoassay, not a machine learning algorithm that requires a "training set." The assay is developed based on chemical and biological principles. If you consider "development" as analogous to training, the inputs would be reagents, antibodies, and known standards used during the assay development and optimization phases.
9. How the ground truth for the training set was established
Not applicable for a traditional immunoassay. For the development of the assay, the "ground truth" for calibrators and controls would be established using highly characterized standards (e.g., gravimetric preparation, reference methods) with known concentrations of 25-OH Vitamin D.
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FEB 1 2 2004
510(k) Summary
SUBMITTED BY:
David Ikeda DiaSorin Inc. 1951 Northwestern Ave. P.O. Box 285 Stillwater, MN 55082-0285 651.351.5592 Voice 651.351.5669 Fax May 05, 2003
This summary of the 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
NAME OF DEVICE: Trade Name Common Names/Descriptions:
Classification Name:
LIAISON® 25 OH Vitamin D Assay Automated chemiluminescent immunoassay for the quantitative determination of 25 OH Vitamin D Vitamin D Test System
PREDICATE DEVICE:
DiaSorin 25-Hydroxyvitamin D 1231 RIA
INTENDED USE: The LIAISON® 25 OH Vitamin D Assay uses chemiluminescent immunoassay (CLIA) technology intended for the quantitative determination of 25hydroxyvitamin D (25-OH-D) and other hydroxylated vitamin D metabolites in human serum or plasma to be 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 an adult population
DEVICE DESCRIPTION: The method for quantitative determination of 25 OH Vitamin D is a direct, competitive chemiluminescence immunoassay (CLIA). Specific antibody to Vitamin D is used for coating magnetic particles (solid phase) and Vitamin D is linked to an isoluminol derivative. During the incubation, 25 OH Vitamin D is dissociated from its binding protein, and competes with labeled Vitamin D for binding sites on the antibody. After the incubation, the unbound material is removed with a wash cycle, Subsequently, the starter reagents are added and a flash chemiluminescent reaction is initiated. The light signal is measured by a photomultiplier as relative light units (RLU) and is inversely proportional to the concentration of 25 OH Vitamin D present in calibrators, controls, or samples.
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| Feature | 25 OH Vitamin D RIA | LIAISON® 25 OH Vitamin D Assay |
|---|---|---|
| Analyte | 25-(OH)-D2/D3 | 25-(OH)-D2/D3 |
| IntendedUse | FOR IN VITRO DIAGNOSTIC USE.This kit is intended for the quantitativedetermination of 25-hydroxyvitamin D(25-OH-D) and other hydroxylatedvitamin D metabolites in human serum orplasma to be used in the assessment ofvitamin D sufficiency. Assay resultsshould be used in conjunction with otherclinical and laboratory data to assist theclinician in making individual patientmanagement decisions in an adultpopulation | FOR IN VITRO DIAGNOSTIC USE.The LIAISON® 25 OH Vitamin D Assayuses chemiluminescent immunoassay(CLIA) technology for the quantitativedetermination of 25-hydroxyvitamin D(25-OH-D) and other hydroxylatedvitamin D metabolites in human serum orplasma to be used in the assessment ofvitamin D sufficiency. Assay resultsshould be used in conjunction with otherclinical and laboratory data to assist theclinician in making individual patientmanagement decisions in an adultpopulation |
| Antisera | Polyclonal specific for 25-(OH)-D2/D3 | Polyclonal specific for 25-(OH)-D2/D3 |
| Tracer | 125I radiolabeled 25-(OH)-D analog | Chemiluminescent ABEI labeled 25-(OH)-D analog |
| Standards | Five concentrations, human serum based,extracted identically to controls andpatient samples | Stored Master Curve based on 10 points,derived from serum based standardsextracted identically to controls andpatient samples |
| Kit | Two levels, human serum based,extracted identically to standards andpatient samples | Two levels, horse serum based, extractedidentically to patient samples |
| Controls | Two levels, human serum based,extracted identically to standards andpatient samples | Two levels, horse serum based, extractedidentically to patient samples |
TECHNOLOGICAL COMPARISON TO PREDICATE:
PERFORMANCE DATA: A summary of performance data is shown below.
| Parameter | Performance Results |
|---|---|
| Sensitivity (analytical) | < 2.0 ng/mL |
| Sensitivity (Functional) | 7.0 ng/mL |
| Total Precision (%CV) | 6% - 13% |
| Recovery (mean) | 109% ± 18% |
| Linearity | $y = 0.98x + 4.1; r = 0.98$ |
| Endogenous Substance Interference | No significant interference observed at the following concentrations: Bilirubin (30 mg/dL); hemoglobin (250 mg/dL); Cholesterol (125 mg/dL); Triglycerides (1000 mg/dL) |
| Sample Types | Serum and EDTA Plasma are equivalent |
| Reference Range | 9.5 to 52.0 ng/mL |
Analytical sensitivity was tested for three lots of materials, giving values less than 2.0 ng/mL for each lot (1.7 ng/mL; 1.6 ng/mL; and 1.5 ng/mL respectively). Functional sensitivity was determined from serial dilutions as 7.0 ng/mL. Total precision was determined to be 6% to 13%CV across the range of the assay according to NCCLS
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Addendum to DiaSorin LIAISON® 25 OH Vitamin D 510(k) Premarket Notification K032844
guidelines. Samples diluted linearly with a correlation coefficient of 0.98. Serum and EDTA plasma matrices gave equivalent results. The 25 OH Vitamin D in samples stored at 2°C - 8°C for up to 5 days gave equivalent results to fresh samples. Samples subjected to up to 5 freeze/thaw cycles also gave equivalent results to fresh samples. No carry-over was observed in testing low concentration samples directly after high concentration samples. The LIAISON® method correlated well with the DiaSorin RIA method, with a correlation coefficient of 0.88. The reference range established using 98 samples from apparently healthy normal volunteers, collected in the southwestern United States in late autumn, was 9.5 ng/mL to 52.0 ng/mL (2.5th to 97.5tt percentiles)
CONCLUSIONS: These data demonstrate the safety and effectiveness of the LIAISON® 25 OH Vitamin D Assay for its intended in vitro diagnostic use.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/3/Picture/1 description: The image shows the seal of the Department of Health & Human Services (USA). The seal features the department's name arranged in a circular pattern around a central emblem. The emblem consists of a stylized representation of three overlapping, curved lines, which are meant to symbolize growth and progress.
Public Health Service
FEB 1 2 2004
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Mr. David M. Ikeda Manager, Regulatory Affairs & Quality Systems Diasorin, Inc. 1951 Northwestern Aveneu P.O. Box 285 Stillwater, MN 55082-0285
K032844 Re:
K0326 11
Trade/Device Name: Liaison® 25-OH Vitamin D Kit Liaison® Control 25-OH Vitamin D Regulation Number: 21 CFR 862.1825 Regulation Name: Vitamin D test system Regulatory Class: Class II Product Code: MRG; JJX Dated: January 6, 2004 Received: January 7, 2004
Dear Mr. Ikeda:
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 for use stated in the 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.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that I·DA'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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
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Page 2
This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.
Sincerely yours,
Jean M. Cooper, MS, DVM.
Yean M. Cooper, MS, D.V.M. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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INDICATIONS FOR USE
510(k) Number (if known):
LIAISON® Control 25 OH Vitamin D Device Name:
Indications for Use:
The LIAISON® Control 25 OH Vitamin D Set is intended for use as assayed quality The LIAISON - Ochtrol 26 OFF accuracy and precision of the LIAISON® 25 OH Vitamin D immunoassay.
(PLEASE DO NOT WRITE BELOW THIS LINE – CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation
Division Sign-Of
| Prescription Use: | ✓ |
|---|---|
| OR Over-the-Counter Use: |
(Per 21 CFR 801.109)
Office of In Vitro Diagnostic Device Evaluation and Safety
Page
510(k) K032844
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| Indications for Use | |
|---|---|
| 510(k) Number (if known): | K03 2844 |
Device Name:
LIAISON® 25-OH Vitamin D Kit
Indications For Use:
This kit is intended for the quantitative determination of 25-hydroxyvitamin D (25-OH-This kit is intended 101 the qualinazires in human serum or plasma to be used in D) and other nythoxyrated framing is now. Assay results should be used in conjunction the assessment of Viammir D barreter of assist the clinician in making individual patient management decisions in an adult population.
(PLEASE DO NOT WRITE BELOW THIS LINE – CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Prescription Use: (Per 21 CFR 801.109)
OR
Over-The-Counter Use:
Carl Benam
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K032844
LS-25D-072 Rev D
Page 2/2
§ 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.