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.

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

AI/ML Overview

The provided document describes the DiaSorin LIAISON® 25 OH Vitamin D TOTAL Assay, a chemiluminescent immunoassay for the quantitative determination of 25-hydroxyvitamin D in human serum. This is an in vitro diagnostic (IVD) device, and the acceptance criteria and study detailed are for its analytical performance, not for clinical diagnostic accuracy in the way a device like an AI for image analysis would be evaluated. As such, concepts like "experts to establish ground truth," "adjudication methods," "MRMC comparative effectiveness," and "standalone AI performance" are not directly applicable to this IVD assay and its performance evaluation. Ground truth in this context refers to established reference methods or known concentrations.

Here's an analysis based on the provided text, adapted for an IVD device:

1. Table of Acceptance Criteria (Inferred) and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" as a table with predefined thresholds, but rather reports the performance characteristics observed in validation studies. The "acceptance criteria" are implied by what is considered acceptable performance for such an assay in the context of regulatory submission (e.g., meeting CLSI guidelines, demonstrating adequate precision, linearity, and minimal interference).

Performance Metric	Inferred Acceptance Criteria (Typical for IVDD)	Reported Device Performance
Method Comparison (Correlation with Predicate)	High correlation coefficient (R > 0.9, ideally closer to 1), slope close to 1, intercept close to 0.	LIAISON® = 1.047 (RIA) + 2.41; R = 0.936 (against DiaSorin 25 OH Vitamin D RIA)
Reproducibility/Precision (Within-Run %CV)	Typically <10% for low concentrations, <5% for higher concentrations.	Sample #5 (7.9 ng/mL): SD 0.6, 7.7%Sample #1 (12.0 ng/mL): SD 0.7, 5.8%Kit Control 1 (18.0 ng/mL): SD 0.9, 5.0%Sample #2 (20.4 ng/mL): SD 1.0, 5.0%Sample #3 (24.3 ng/mL): SD 1.2, 5.0%Sample #4 (56.8 ng/mL): SD 2.9, 5.0%Kit Control 2 (61.8 ng/mL): SD 3.0, 4.9%Sample #6 (112.1 ng/mL): SD 5.4, 4.8%
Reproducibility/Precision (Total %CV)	Typically <15% for low concentrations, <10% for higher concentrations.	Sample #5 (7.9 ng/mL): SD 1.0, 12.6%Sample #1 (12.0 ng/mL): SD 1.3, 11.1%Kit Control 1 (18.0 ng/mL): SD 1.7, 9.7%Sample #2 (20.4 ng/mL): SD 2.1, 10.4%Sample #3 (24.3 ng/mL): SD 2.6, 10.6%Sample #4 (56.8 ng/mL): SD 5.8, 10.3%Kit Control 2 (61.8 ng/mL): SD 5.8, 9.5%Sample #6 (112.1 ng/mL): SD 12.2, 10.8%
Dilution Linearity (R)	R close to 1 (e.g., >0.99)	Observed = Expected 1.01x - 0.180; R = 0.995
Functional Sensitivity	Defined by manufacturer based on clinical utility; typically where %CV exceeds 20%.	≤4.0 ng/mL (defined as the concentration at which %CV exceeds 20%)
Interfering Substances (Change in Results)	Typically ≤10% change in results at specified concentrations.	Hemolyzed: ≤10% change up to 200 mg/dL hemoglobinLipemic: ≤10% change up to 589 mg/dL triglyceridesIcteric: ≤10% change up to 40 mg/dL conjugated bilirubinIcteric: ≤10% change up to 40 mg/dL unconjugated bilirubinCholesterol: ≤10% change up to 301 mg/dLUric acid: ≤10% change up to 20 mg/dLTotal Protein: ≤10% change up to 12 g/dL

2. Sample Sizes and Data Provenance for Test Set (Validation Studies)

Method Comparison: 587 samples.
- Data Provenance: Samples were obtained from a clinical reference laboratory. The country of origin is not specified but given DiaSorin Inc.'s location in Minnesota, USA, and the FDA submission, it's likely primarily US data. It's retrospective (collected for testing).
Reproducibility/Precision: A coded panel of 6 serum samples, plus 2 levels of kit controls. The exact number of replicates per sample/control at each site is not given, but it was a 20-day study.
- Data Provenance: Samples prepared by DiaSorin Inc. (likely US). The study was performed at DiaSorin Inc. and 2 external sites.
Dilution Linearity: Two (2) serum pools.
- Data Provenance: Not explicitly stated, but likely laboratory-prepared serum pools.
Functional Sensitivity: Samples prepared at nominal concentrations of 2.0 - 14.0 ng/mL.
- Data Provenance: Not explicitly stated, but likely laboratory-prepared samples.
Interfering Substances: Specific substances at various concentrations.
- Data Provenance: Not explicitly stated, but likely laboratory-prepared samples or spiked samples.

3. Number of Experts and their Qualifications to Establish Ground Truth for the Test Set

This requirement is not applicable to this type of IVD device evaluation for analytical performance. The "ground truth" for analytical studies is established by:

Using a well-established reference method (e.g., the predicate DiaSorin 25 OH Vitamin D RIA for method comparison).
Using gravimetrically prepared or certified reference materials for precision, linearity, and functional sensitivity.
Spiking experiments for interfering substances.

There are no human experts "adjudicating" diagnostic outputs in this context; it's a quantitative measurement device.

4. Adjudication Method for the Test Set

Not applicable. As described above, this is an analytical performance study, not a diagnostic accuracy study requiring adjudication.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

No. This is an automated immunoassay, not an AI-assisted diagnostic imaging device that involves human reader interpretation. Therefore, MRMC studies and "human readers improve with AI vs without AI assistance" are not relevant.

6. If a Standalone (algorithm only without human-in-the-loop performance) was done

Yes, the entire performance evaluation presented is a standalone (algorithm only) performance assessment, as it describes the analytical characteristics of the LIAISON® 25 OH Vitamin D TOTAL Assay system itself, without human interpretation as part of the primary result generation process. The device provides a quantitative number.

7. The Type of Ground Truth Used

Method Comparison: The DiaSorin 25 OH Vitamin D RIA (a previously cleared predicate device) served as the comparative "ground truth" or reference method.
Reproducibility/Precision: The known concentrations of the prepared serum samples and controls served as the reference for evaluating precision.
Dilution Linearity: The expected concentrations based on dilution of known pools served as the reference.
Functional Sensitivity: The known nominal concentrations of prepared samples were used.
Interfering Substances: The known concentrations of added interfering substances were used to test their impact on the assay results.

8. The Sample Size for the Training Set

This is not applicable in the typical sense for this device. The LIAISON® 25 OH Vitamin D TOTAL Assay is a chemiluminescent immunoassay, not a machine learning or AI algorithm that undergoes "training" on a dataset in the way an AI model would. Its "training" is in the form of R&D and optimization of the assay reagents and protocols to achieve desired analytical performance. There isn't a "training set" of patient data for an algorithm.

9. How the Ground Truth for the Training Set was Established

Not applicable for the same reasons as (8). The assay's performance is optimized through traditional wet-lab biochemistry and immunoassay development, not algorithm training data.

Summary

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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 (651) 439-9710 Fax (651) 351-5669 Email: mari.mever@diasorin.com

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(K071480)

DEVICE DESCRIPTION:

INTENDED USE:

KIT DESCRIPTION:

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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(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

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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.

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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).

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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 (301) 796-5450. 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 (800) 638-2041 or (301) 796-5680 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

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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

Regulation Number and Section

§ 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.