LIAISON 25 OH VITAMIN D TOTAL ASSAY

K112725 · DiaSorin, Inc. · MRG · Jan 20, 2012 · Clinical Chemistry

Device Facts

• Record ID: K112725
• Device Name: LIAISON 25 OH VITAMIN D TOTAL ASSAY
• Applicant: DiaSorin, Inc.
• Product Code: MRG · Clinical Chemistry
• Decision Date: Jan 20, 2012
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1825
• Device Class: Class 2

Intended Use

The LIAISON® 25 OH Vitamin D TOTAL Assay uses chemiluminescent immunoassay (CLIA) technology for the quantitative determination of 25-hydroxyvitamin D and other hydroxylated vitamin D metabolites in human serum to be used in the assessment of vitamin D sufficiency. Assay results should be used in conjunction with other clinical or laboratory data to assist the clinician in making individual patient management decisions in an adult population.

Device Story

The LIAISON® 25 OH Vitamin D TOTAL Assay is an in vitro diagnostic chemiluminescent immunoassay (CLIA) used on the LIAISON® Analyzer family. It measures 25-hydroxyvitamin D and other hydroxylated metabolites in human serum. The assay uses a direct competitive binding principle: 25 OH Vitamin D is dissociated from binding proteins and captured by specific antibodies on a solid phase; a vitamin D-isoluminol tracer is added; unbound material is washed away. Starter reagents initiate a flash chemiluminescent reaction. A photomultiplier measures the light signal (RLU), which is inversely proportional to the analyte concentration. The device is used in clinical laboratory settings by trained personnel. Results assist clinicians in assessing vitamin D sufficiency and managing adult patients. Modifications in this version include changes to the magnetic particle surface and assay buffer to reduce interference from rare heterophilic antibodies.

Clinical Evidence

Bench testing only. Precision/reproducibility study (N=160 replicates per sample across 3 sites) showed total CVs ranging from 9.5% to 12.6%. Linearity confirmed across 4–150 ng/mL range (R²=0.997). Method comparison with RIA predicate (N=587) yielded slope 1.047, intercept 2.41, correlation 0.936. Reference range study (N=396) established baseline values across diverse US populations.

Technological Characteristics

Quantitative chemiluminescent immunoassay (CLIA). Components: magnetic particles coated with anti-25 OH Vitamin D antibody, assay buffer (ethanol, surfactants, ProClin® 300), and isoluminol-conjugated 25 OH Vitamin D tracer. Measuring range: 4–150 ng/mL. Instrument: LIAISON® Analyzer. Standards referenced: CLSI EP5-A2 (precision), EP6-A (linearity), EP7-A2 (interference).

Indications for Use

Indicated for the quantitative determination of 25-hydroxyvitamin D and other hydroxylated vitamin D metabolites in human serum for the assessment of vitamin D sufficiency in an adult population.

Regulatory Classification

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.

Special Controls

*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.

Predicate Devices

• LIAISON® 25 OH Vitamin D TOTAL Assay (k071480)

Reference Devices

• DiaSorin 25-hydroxyVitamin D 125I RIA (k983617)

Submission Summary (Full Text)

{0}------------------------------------------------

DiaSorin LIAISON® 25 OH Vitamin D TOTAL Premarket Notification

# K112725

JAN 2 0 2012

#### 510(k) SUMMARY

# SUBMITTED BY:

Mari Meyer Senior Manager Requlatory Affairs DiaSorin Inc. 1951 Northwestern Avenue P.O. Box 285 Stillwater, MN 55082-0285 Phone [phone] Fax [phone] Email: [e-mail]

# NAME OF DEVICE:

| Trade Name: | LIAISON® 25 OH Vitamin D TOTAL Assay |
|----------------------------|---------------------------------------------------|
| Common Names/Descriptions: | Vitamin D Reagents |
| Classification Names: | Vitamin D Test System |
| Classification Number: | 862.1825 |
| Product Code: | MRG |
| PREDICATE DEVICE: | LIAISON® 25 OH Vitamin D TOTAL Assay<br>(K071480) |

# DEVICE DESCRIPTION:

#### INTENDED USE:

The LIAISON® 25 OH Vitamin D TOTAL Assay uses chemiluminescent immunoassay (CLIA) technology for the quantitative determination of 25-hydroxyvitamin D and other hydroxylated vitamin D metabolites in human serum to be used in the assessment of vitamin D sufficiency using the LIAISON® Analyzer family. Assay results should be used in conjunction with other clinical or laboratory data to assist the clinician in making individual patient management decisions in an adult population.

## KIT DESCRIPTION:

The LIAISON® 25 OH Vitamin D assay is a direct competitive chemiluminescence immunoassay (CLIA) for quantitative determination of total 25 OH vitamin D in serum. During the first incubation. 25 OH Vitamin D is dissociated from its binding protein and binds to the specific antibody on the solid phase. After 10 minutes the tracer, (vitamin D linked to an isoluminol derivative) is added. After a second10 minute incubation, the unbound material is removed with a wash cycle. Subsequently, the starter reagents are added to initiate a flash chemiluminescent reaction. The light signal is measured by a

{1}------------------------------------------------

photomultiplier as relative light units (RLU) and is inversely proportional to the concentration of 25 OH vitamin D present in calibrators, controls, or samples.

Changes were made to the assay's magnetic particle surface and the Assay Buffer formulation to reduce reaction with rare heterophilic antibodies.

## PERFORMANCE DATA:

#### Method Comparison:

A method comparison study was performed following CLSI EP9-A2. In the study, samples were obtained from a clinical reference laboratory. A total of 587 samples were tested by LIAISON® 25 OH Vitamin D TOTAL and by DiaSorin 25 OH Vitamin D RIA. Linear regression analyses were performed on the results across the measuring range of the LIAISON® assay. The resulting regression equation was: LIAISON® = 1.047 (RIA) + 2.41; R = 0.936.

## Reproducibility/Precision:

A 20 day reproducibility/precision study was performed at DiaSorin Inc. and 2 external sites. A coded panel comprised of 6 serum samples was prepared by DiaSorin Inc. The LIAISON® 25 OH Vitamin D TOTAL controls (2 levels) were also tested in the study. The CLSI document EP15-A2 was consulted in the preparation of the testing protocol.

| | Mean<br>(ng/mL) | Intra-Run | | Total | |
|---------------|-----------------|-----------|------|-------|-------|
| Sample ID | | SD | %CV | SD | %CV |
| Sample #5 | 7.9 | 0.6 | 7.7% | 1.0 | 12.6% |
| Sample #1 | 12.0 | 0.7 | 5.8% | 1.3 | 11.1% |
| Kit Control 1 | 18.0 | 0.9 | 5.0% | 1.7 | 9.7% |
| Sample #2 | 20.4 | 1.0 | 5.0% | 2.1 | 10.4% |
| Sample #3 | 24.3 | 1.2 | 5.0% | 2.6 | 10.6% |
| Sample #4 | 56.8 | 2.9 | 5.0% | 5.8 | 10.3% |
| Kit Control 2 | 61.8 | 3.0 | 4.9% | 5.8 | 9.5% |
| Sample #6 | 112.1 | 5.4 | 4.8% | 12.2 | 10.8% |

The 20 day results for the 3 sites are summarized in the following table.

## Dilution Linearity:

Two (2) serum pools were diluted and analyzed with 1 LIAISON® 25 OH Vitamin D TOTAL Assay kit lots following CLSI EP6-A. The results for each sample were analvzed by a linear regression of observed Vitamin D concentration versus expected Vitamin D concentration. The resulting regression equation is: Observed = Expected 1.01x -0.180; R = 0.995.

# Functional Sensitivity

The functional sensitivity is defined as the dose concentration at which the %CV exceeds 20%, was evaluated according to CLSI EP17-A. Samples were prepared at

{2}------------------------------------------------

nominal concentrations of 2.0 - 14.0 ng/mL and assayed in multiple runs to determine mean concentration and %CV. Sample concentration was plotted against %CV and a regression was prepared to determine the functional sensitivity. The derived functional sensitivity from the regression equation is ≤4.0 ng/mL.

#### Interfering Substances

Interfering substances were tested in the LIAISON® 25 OH Vitamin D Assay. The results are presented in below.

| Specimens That Are | Demonstrate $\leq$ 10% change in Results Up To |
|------------------------|------------------------------------------------|
| Hemolyzed | 200 mg/dL of hemoglobin |
| Lipemic | 589 mg/dL of triglycerides |
| Icteric | 40 mg/dL of conjugated bilirubin |
| Icteric | 40 mg/dL of unconjugated bilirubin |
| Specimens That Contain | Demonstrate $\leq$ 10% change in Results Up To |
| Cholesterol | 301 mg/dL |
| Uric acid | 20 mg/dL |
| Total Protein | 12 g/dL |

## CONCLUSION:

The material submitted in this premarket notification is complete and supports the basis for substantial equivalence. The labeling is sufficient and satisfies the requirements of 21 CFR Part 809.10.

{3}------------------------------------------------

Image /page/3/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 a stylized image of a human figure, represented by three overlapping profiles, suggesting a sense of community and care.

10903 New Hampshire Avenue Silver Spring, MD 20993

DiaSorin Inc c/o Judi Smith LLC P.O. Box 103 Baldwin, MD 21013

JAN 2 0 2012

k112725 Re:

Trade Name: LIAISON® 25 OH Vitamin D TOTAL Assay Regulation Number: 21 CFR §862.1825 Regulation Name: Vitamin D Test System Regulatory Class: Class II Product Codes: MRG Dated: December 20, 2011 Received: December 22, 2011

Dear Ms. Smith:

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.

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 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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

{4}------------------------------------------------

#### Page 2

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please 11 you assno if In Vitro Diagnostic Device Evaluation and Safety at [phone]. Also, commor the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at (301) Other of Darrellier and regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/Medical

Devices/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 rou may of amall Manufacturers, International and Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm

Sincerely yours,

Signature

Couriney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

{5}------------------------------------------------

#### INDICATION FOR USE 5

510(k) Number (if known):

LIAISON® 25 OH Vitamin D TOTAL Assay Device Name:

Indication For Use:

The LIAISON® 25 OH Vitamin D TOTAL Assay uses chemiluminescent immunoassay (CLIA) technology for the quantitative determination of 25hydroxyvitamin D and other hydroxylated vitamin D metabolites in human serum to be used in the assessment of vitamin D sufficiency. Assay results should be used in conjunction with other clinical or laboratory data to assist the clinician in making individual patient management decisions in an adult population.

Over the Counter Use _ And/Or Prescription Use_ × (21 CFR Part 801 Subpart C) (21 CFR Part 801 Subpart D) (PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)

Quth Chelen

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) 1\ 2725

Page 1 of 1